Feline APOBEC3s, Barriers to Cross-Species Transmission of FIV?

PubMed Central

Zhang, Zeli; Gu, Qinyong; Marino, Daniela; Lee, Kyeong-Lim; Kong, Il-Keun; Häussinger, Dieter; Münk, Carsten

2018-01-01

The replication of lentiviruses highly depends on host cellular factors, which defines their species-specific tropism. Cellular restriction factors that can inhibit lentiviral replication were recently identified. Feline immunodeficiency virus (FIV) was found to be sensitive to several feline cellular restriction factors, such as apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3) and tetherin, but FIV evolved to counteract them. Here, we describe the molecular mechanisms by which feline APOBEC3 restriction factors inhibit FIV replication and discuss the molecular interaction of APOBEC3 proteins with the viral antagonizing protein Vif. We speculate that feline APOBEC3 proteins could explain some of the observed FIV cross-species transmissions described in wild Felids. PMID:29642583

Heroin use is associated with lower levels of restriction factors and type I interferon expression and facilitates HIV-1 replication.

PubMed

Zhu, Jia-Wu; Liu, Feng-Liang; Mu, Dan; Deng, De-Yao; Zheng, Yong-Tang

Heroin use is associated with increased incidence of infectious diseases such as HIV-1 infection, as a result of immunosuppression to a certain extent. Host restriction factors are recently identified cellular proteins with potent antiviral activities. Whether heroin use impacts on the in vivo expression of restriction factors that result in facilitating HIV-1 replication is poorly understood. Here we recruited 432 intravenous drug users (IDUs) and 164 non-IDUs at high-risk behaviors. Based on serological tests, significantly higher prevalence of HIV-1 infection was observed among IDUs compared with non-IDUs. We included those IDUs and non-IDUs without HIV-1 infection, and found IDUs had significantly lower levels of TRIM5α, TRIM22, APOBEC3G, and IFN-α, -β expression than did non-IDUs. We also directly examined plasma viral load in HIV-1 mono-infected IDUs and non-IDUs and found HIV-1 mono-infected IDUs had significantly higher plasma viral load than did non-IDUs. Moreover, intrinsically positive correlation between type I interferon and TRIM5α or TRIM22 was observed, however, which was dysregulated following heroin use. Collectively, heroin use benefits HIV-1 replication that may be partly due to suppression of host restriction factors and type I interferon expression. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Nuclear Envelope Protein SUN2 Promotes Cyclophilin-A-Dependent Steps of HIV Replication

PubMed Central

Lahaye, Xavier; Satoh, Takeshi; Gentili, Matteo; Cerboni, Silvia; Silvin, Aymeric; Conrad, Cécile; Ahmed-Belkacem, Abdelhakim; Rodriguez, Elisa C.; Guichou, Jean-François; Bosquet, Nathalie; Piel, Matthieu; Le Grand, Roger; King, Megan C.; Pawlotsky, Jean-Michel; Manel, Nicolas

2016-01-01

Summary During the early phase of replication, HIV reverse transcribes its RNA and crosses the nuclear envelope while escaping host antiviral defenses. The host factor Cyclophilin A (CypA) is essential for these steps and binds the HIV capsid; however, the mechanism underlying this effect remains elusive. Here, we identify related capsid mutants in HIV-1, HIV-2, and SIVmac that are restricted by CypA. This antiviral restriction of mutated viruses is conserved across species and prevents nuclear import of the viral cDNA. Importantly, the inner nuclear envelope protein SUN2 is required for the antiviral activity of CypA. We show that wild-type HIV exploits SUN2 in primary CD4+ T cells as an essential host factor that is required for the positive effects of CypA on reverse transcription and infection. Altogether, these results establish essential CypA-dependent functions of SUN2 in HIV infection at the nuclear envelope. PMID:27149839

Chlamydia muridarum evades growth restriction by the IFN-gamma-inducible host resistance factor Irgb10.

PubMed

Coers, Jörn; Bernstein-Hanley, Isaac; Grotsky, David; Parvanova, Iana; Howard, Jonathan C; Taylor, Gregory A; Dietrich, William F; Starnbach, Michael N

2008-05-01

Chlamydiae are obligate intracellular bacterial pathogens that exhibit a broad range of host tropism. Differences in host tropism between Chlamydia species have been linked to host variations in IFN-gamma-mediated immune responses. In mouse cells, IFN-gamma can effectively restrict growth of the human pathogen Chlamydia trachomatis but fails to control growth of the closely related mouse pathogen Chlamydia muridarum. The ability of mouse cells to resist C. trachomatis replication is largely dependent on the induction of a family of IFN-gamma-inducible GTPases called immunity-related GTPases or IRGs. In this study we demonstrate that C. muridarum can specifically evade IRG-mediated host resistance. It has previously been suggested that C. muridarum inactivates the IRG protein Irga6 (Iigp1) to dampen the murine immune response. However, we show that Irga6 is dispensable for the control of C. trachomatis replication. Instead, an effective IFN-gamma response to C. trachomatis requires the IRG proteins Irgm1 (Lrg47), Irgm3 (Igtp), and Irgb10. Ectopic expression of Irgb10 in the absence of IFN-gamma is sufficient to reduce intracellular growth of C. trachomatis but fails to restrict growth of C. muridarum, indicating that C. muridarum can specifically evade Irgb10-driven host responses. Importantly, we find that Irgb10 protein intimately associates with inclusions harboring C. trachomatis but is absent from inclusions formed by C. muridarum. These data suggest that C. muridarum has evolved a mechanism to escape the murine IFN-gamma response by restricting access of Irgb10 and possibly other IRG proteins to the inclusion.

H5N1 Influenza A Virus PB1-F2 Relieves HAX-1-Mediated Restriction of Avian Virus Polymerase PA in Human Lung Cells.

PubMed

Mazel-Sanchez, B; Boal-Carvalho, I; Silva, F; Dijkman, R; Schmolke, M

2018-06-01

Highly pathogenic influenza A viruses (IAV) from avian hosts were first reported to directly infect humans 20 years ago. However, such infections are rare events, and our understanding of factors promoting or restricting zoonotic transmission is still limited. One accessory protein of IAV, PB1-F2, was associated with pathogenicity of pandemic and zoonotic IAV. This short (90-amino-acid) peptide does not harbor an enzymatic function. We thus identified host factors interacting with H5N1 PB1-F2, which could explain its importance for virulence. PB1-F2 binds to HCLS1-associated protein X1 (HAX-1), a recently identified host restriction factor of the PA subunit of IAV polymerase complexes. We demonstrate that the PA of a mammal-adapted H1N1 IAV is resistant to HAX-1 imposed restriction, while the PA of an avian-origin H5N1 IAV remains sensitive. We also showed HAX-1 sensitivity for PAs of A/Brevig Mission/1/1918 (H1N1) and A/Shanghai/1/2013 (H7N9), two avian-origin zoonotic IAV. Inhibition of H5N1 polymerase by HAX-1 can be alleviated by its PB1-F2 through direct competition. Accordingly, replication of PB1-F2-deficient H5N1 IAV is attenuated in the presence of large amounts of HAX-1. Mammal-adapted H1N1 and H3N2 viruses do not display this dependence on PB1-F2 for efficient replication in the presence of HAX-1. We propose that PB1-F2 plays a key role in zoonotic transmission of avian H5N1 IAV into humans. IMPORTANCE Aquatic and shore birds are the natural reservoir of influenza A viruses from which the virus can jump into a variety of bird and mammal host species, including humans. H5N1 influenza viruses are a good model for this process. They pose an ongoing threat to human and animal health due to their high mortality rates. However, it is currently unclear what restricts these interspecies jumps on the host side or what promotes them on the virus side. Here we show that a short viral peptide, PB1-F2, helps H5N1 bird influenza viruses to overcome a human restriction factor of the viral polymerase complex HAX-1. Interestingly, we found that human influenza A virus polymerase complexes are already adapted to HAX-1 and do not require this function of PB1-F2. We thus propose that a functional full-length PB1-F2 supports direct transmission of bird viruses into humans. Copyright © 2018 Mazel-Sanchez et al.

Antagonism of the Protein Kinase R Pathway in Human Cells by Rhesus Cytomegalovirus.

PubMed

Child, Stephanie J; Hickson, Sarah E; Bayer, Avraham; Malouli, Daniel; Früh, Klaus; Geballe, Adam P

2018-03-15

While cytomegalovirus (CMV) infections are often limited in host range by lengthy coevolution with a single host species, a few CMVs are known to deviate from this rule. For example, rhesus macaque CMV (RhCMV), a model for human CMV (HCMV) pathogenesis and vaccine development, can replicate in human cells, as well as in rhesus cells. Both HCMV and RhCMV encode species-specific antagonists of the broadly acting host cell restriction factor protein kinase R (PKR). Although the RhCMV antagonist of PKR, rTRS1, has very limited activity against human PKR, here, we show it is essential for RhCMV replication in human cells because it prevents human PKR from phosphorylating the translation initiation factor eIF2α, thereby allowing continued translation and viral replication. Although rTRS1 is necessary for RhCMV replication, it is not sufficient to rescue replication of HCMV lacking its own PKR antagonists in human fibroblasts. However, overexpression of rTRS1 in human fibroblasts enabled HCMV expressing rTRS1 to replicate, indicating that elevated levels or early expression of a weak antagonist can counteract a resistant restriction factor like human PKR. Exploring potential mechanisms that might allow RhCMV to replicate in human cells revealed that RhCMV makes no less double-stranded RNA than HCMV. Rather, in human cells, RhCMV expresses rTRS1 at levels 2 to 3 times higher than those of the HCMV-encoded PKR antagonists during HCMV infection. These data suggest that even a modest increase in expression of this weak PKR antagonist is sufficient to enable RhCMV replication in human cells. IMPORTANCE Rhesus macaque cytomegalovirus (RhCMV) offers a valuable model for studying congenital human cytomegalovirus (HCMV) pathogenesis and vaccine development. Therefore, it is critical to understand variations in how each virus infects and affects its host species to be able to apply insights gained from the RhCMV model to HCMV. While HCMV is capable only of infecting cells from humans and very closely related species, RhCMV displays a wider host range, including human as well as rhesus cells. RhCMV expresses an antagonist of a broadly acting antiviral factor present in all mammalian cells, and its ability to counter both the rhesus and human versions of this host factor is a key component of RhCMV's ability to cross species barriers. Here, we examine the molecular mechanisms that allow this RhCMV antagonist to function against a human restriction factor. Copyright © 2018 American Society for Microbiology.

Along for the ride or missing it altogether: exploring the host specificity and diversity of haemogregarines in the Canary Islands.

PubMed

Tomé, Beatriz; Pereira, Ana; Jorge, Fátima; Carretero, Miguel A; Harris, D James; Perera, Ana

2018-03-19

Host-parasite relationships are expected to be strongly shaped by host specificity, a crucial factor in parasite adaptability and diversification. Because whole host communities have to be considered to assess host specificity, oceanic islands are ideal study systems given their simplified biotic assemblages. Previous studies on insular parasites suggest host range broadening during colonization. Here, we investigate the association between one parasite group (haemogregarines) and multiple sympatric hosts (of three lizard genera: Gallotia, Chalcides and Tarentola) in the Canary Islands. Given haemogregarine characteristics and insular conditions, we hypothesized low host specificity and/or occurrence of host-switching events. A total of 825 samples were collected from the three host taxa inhabiting the seven main islands of the Canarian Archipelago, including locations where the different lizards occurred in sympatry. Blood slides were screened to assess prevalence and parasitaemia, while parasite genetic diversity and phylogenetic relationships were inferred from 18S rRNA gene sequences. Infection levels and diversity of haplotypes varied geographically and across host groups. Infections were found in all species of Gallotia across the seven islands, in Tarentola from Tenerife, La Gomera and La Palma, and in Chalcides from Tenerife, La Gomera and El Hierro. Gallotia lizards presented the highest parasite prevalence, parasitaemia and diversity (seven haplotypes), while the other two host groups (Chalcides and Tarentola) harbored one haplotype each, with low prevalence and parasitaemia levels, and very restricted geographical ranges. Host-sharing of the same haemogregarine haplotype was only detected twice, but these rare instances likely represent occasional cross-infections. Our results suggest that: (i) Canarian haemogregarine haplotypes are highly host-specific, which might have restricted parasite host expansion; (ii) haemogregarines most probably reached the Canary Islands in three colonization events with each host genus; and (iii) the high number of parasite haplotypes infecting Gallotia hosts and their restricted geographical distribution suggest co-diversification. These findings contrast with our expectations derived from results on other insular parasites, highlighting how host specificity depends on parasite characteristics and evolutionary history.

Identification of Host-Targeted Small Molecules That Restrict Intracellular Mycobacterium tuberculosis Growth

PubMed Central

Silvis, Melanie R.; Luo, Samantha S.; Sogi, Kimberly; Vokes, Martha; Bray, Mark-Anthony; Carpenter, Anne E.; Moore, Christopher B.; Siddiqi, Noman; Rubin, Eric J.; Hung, Deborah T.

2014-01-01

Mycobacterium tuberculosis remains a significant threat to global health. Macrophages are the host cell for M. tuberculosis infection, and although bacteria are able to replicate intracellularly under certain conditions, it is also clear that macrophages are capable of killing M. tuberculosis if appropriately activated. The outcome of infection is determined at least in part by the host-pathogen interaction within the macrophage; however, we lack a complete understanding of which host pathways are critical for bacterial survival and replication. To add to our understanding of the molecular processes involved in intracellular infection, we performed a chemical screen using a high-content microscopic assay to identify small molecules that restrict mycobacterial growth in macrophages by targeting host functions and pathways. The identified host-targeted inhibitors restrict bacterial growth exclusively in the context of macrophage infection and predominantly fall into five categories: G-protein coupled receptor modulators, ion channel inhibitors, membrane transport proteins, anti-inflammatories, and kinase modulators. We found that fluoxetine, a selective serotonin reuptake inhibitor, enhances secretion of pro-inflammatory cytokine TNF-α and induces autophagy in infected macrophages, and gefitinib, an inhibitor of the Epidermal Growth Factor Receptor (EGFR), also activates autophagy and restricts growth. We demonstrate that during infection signaling through EGFR activates a p38 MAPK signaling pathway that prevents macrophages from effectively responding to infection. Inhibition of this pathway using gefitinib during in vivo infection reduces growth of M. tuberculosis in the lungs of infected mice. Our results support the concept that screening for inhibitors using intracellular models results in the identification of tool compounds for probing pathways during in vivo infection and may also result in the identification of new anti-tuberculosis agents that work by modulating host pathways. Given the existing experience with some of our identified compounds for other therapeutic indications, further clinically-directed study of these compounds is merited. PMID:24586159

Poxvirus Host Range Genes and Virus–Host Spectrum: A Critical Review

PubMed Central

Oliveira, Graziele Pereira; Rodrigues, Rodrigo Araújo Lima; Lima, Maurício Teixeira; Drumond, Betânia Paiva; Abrahão, Jônatas Santos

2017-01-01

The Poxviridae family is comprised of double-stranded DNA viruses belonging to nucleocytoplasmic large DNA viruses (NCLDV). Among the NCLDV, poxviruses exhibit the widest known host range, which is likely observed because this viral family has been more heavily investigated. However, relative to each member of the Poxviridae family, the spectrum of the host is variable, where certain viruses can infect a large range of hosts, while others are restricted to only one host species. It has been suggested that the variability in host spectrum among poxviruses is linked with the presence or absence of some host range genes. Would it be possible to extrapolate the restriction of viral replication in a specific cell lineage to an animal, a far more complex organism? In this study, we compare and discuss the relationship between the host range of poxvirus species and the abundance/diversity of host range genes. We analyzed the sequences of 38 previously identified and putative homologs of poxvirus host range genes, and updated these data with deposited sequences of new poxvirus genomes. Overall, the term host range genes might not be the most appropriate for these genes, since no correlation between them and the viruses’ host spectrum was observed, and a change in nomenclature should be considered. Finally, we analyzed the evolutionary history of these genes, and reaffirmed the occurrence of horizontal gene transfer (HGT) for certain elements, as previously suggested. Considering the data presented in this study, it is not possible to associate the diversity of host range factors with the amount of hosts of known poxviruses, and this traditional nomenclature creates misunderstandings. PMID:29112165

Targeting CTCF to Control Virus Gene Expression: A Common Theme amongst Diverse DNA Viruses.

PubMed

Pentland, Ieisha; Parish, Joanna L

2015-07-06

All viruses target host cell factors for successful life cycle completion. Transcriptional control of DNA viruses by host cell factors is important in the temporal and spatial regulation of virus gene expression. Many of these factors are recruited to enhance virus gene expression and thereby increase virus production, but host cell factors can also restrict virus gene expression and productivity of infection. CCCTC binding factor (CTCF) is a host cell DNA binding protein important for the regulation of genomic chromatin boundaries, transcriptional control and enhancer element usage. CTCF also functions in RNA polymerase II regulation and in doing so can influence co-transcriptional splicing events. Several DNA viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), Epstein-Barr virus (EBV) and human papillomavirus (HPV) utilize CTCF to control virus gene expression and many studies have highlighted a role for CTCF in the persistence of these diverse oncogenic viruses. CTCF can both enhance and repress virus gene expression and in some cases CTCF increases the complexity of alternatively spliced transcripts. This review article will discuss the function of CTCF in the life cycle of DNA viruses in the context of known host cell CTCF functions.

Highlights of the DNA cutters: a short history of the restriction enzymes

PubMed Central

Loenen, Wil A. M.; Dryden, David T. F.; Raleigh, Elisabeth A.; Wilson, Geoffrey G.; Murray, Noreen E.

2014-01-01

In the early 1950’s, ‘host-controlled variation in bacterial viruses’ was reported as a non-hereditary phenomenon: one cycle of viral growth on certain bacterial hosts affected the ability of progeny virus to grow on other hosts by either restricting or enlarging their host range. Unlike mutation, this change was reversible, and one cycle of growth in the previous host returned the virus to its original form. These simple observations heralded the discovery of the endonuclease and methyltransferase activities of what are now termed Type I, II, III and IV DNA restriction-modification systems. The Type II restriction enzymes (e.g. EcoRI) gave rise to recombinant DNA technology that has transformed molecular biology and medicine. This review traces the discovery of restriction enzymes and their continuing impact on molecular biology and medicine. PMID:24141096

Highlights of the DNA cutters: a short history of the restriction enzymes.

PubMed

Loenen, Wil A M; Dryden, David T F; Raleigh, Elisabeth A; Wilson, Geoffrey G; Murray, Noreen E

2014-01-01

In the early 1950's, 'host-controlled variation in bacterial viruses' was reported as a non-hereditary phenomenon: one cycle of viral growth on certain bacterial hosts affected the ability of progeny virus to grow on other hosts by either restricting or enlarging their host range. Unlike mutation, this change was reversible, and one cycle of growth in the previous host returned the virus to its original form. These simple observations heralded the discovery of the endonuclease and methyltransferase activities of what are now termed Type I, II, III and IV DNA restriction-modification systems. The Type II restriction enzymes (e.g. EcoRI) gave rise to recombinant DNA technology that has transformed molecular biology and medicine. This review traces the discovery of restriction enzymes and their continuing impact on molecular biology and medicine.

Feeding preferences and performance of an aquatic lepidopteran on macrophytes: plant hosts as food and habitat.

PubMed

Dorn, Nathan J; Cronin, Greg; Lodge, David M

2001-08-01

Although host preferences in phytophagous insects may be generated by several factors, few studies have simultaneously examined several potential host choice determinants. In this study we tested the impact of the following potential host choice determinants on host preference of the semi-aquatic lepidopteran Munroessa gyralis (Pyralidae): growth on different host plants; protein content, polyphenolic content, toughness, and chemical extracts of different host plants; prior feeding experience; and predation pressure on the caterpillar by fishes. Two water lilies, Brasenia schreberi and Nymphaea odorata, were preferred in cafeteria-style feeding experiments over 14 other species of vascular plants. The most preferred water lily (Brasenia) also afforded the fastest growth relative to three other species on which growth was measured. Feeding preferences across species were unrelated to protein content, polyphenolic content, or toughness. Domiciles constructed by caterpillars from leaf fragments were protective from field assemblages of fishes, but domiciles made from preferred or unpreferred host species conferred no significant protection from fish in the laboratory. Caterpillars responded positively to chemical cues of water lilies, and prior feeding experience increased preference for an otherwise unpreferred water lily (Nuphar advena) within the life-span of individual caterpillars. M. gyralis is a generalist herbivore exhibiting modest preference induction and preferences for and among members of the family Nymphaeaceae. Our results suggest that relative growth rates, chemical cues, and previous feeding experience are important factors determining feeding preference. Protein content, polyphenolic content, and toughness appear less important, and the importance of fish predators remains in question. As pupation seems to occur exclusively on Nymphaea, we suggest that host use may be restricted due to life-stage-specific developmental constraints that are not apparent from the results of growth or preference assays. It is currently unknown how often specific life-stages may restrict host use, but our work suggests this as a potentially important area of inquiry.

Salmonella Pathogenicity and Host Adaptation in Chicken-Associated Serovars

PubMed Central

Johnson, Timothy J.; Ricke, Steven C.; Nayak, Rajesh; Danzeisen, Jessica

2013-01-01

SUMMARY Enteric pathogens such as Salmonella enterica cause significant morbidity and mortality. S. enterica serovars are a diverse group of pathogens that have evolved to survive in a wide range of environments and across multiple hosts. S. enterica serovars such as S. Typhi, S. Dublin, and S. Gallinarum have a restricted host range, in which they are typically associated with one or a few host species, while S. Enteritidis and S. Typhimurium have broad host ranges. This review examines how S. enterica has evolved through adaptation to different host environments, especially as related to the chicken host, and continues to be an important human pathogen. Several factors impact host range, and these include the acquisition of genes via horizontal gene transfer with plasmids, transposons, and phages, which can potentially expand host range, and the loss of genes or their function, which would reduce the range of hosts that the organism can infect. S. Gallinarum, with a limited host range, has a large number of pseudogenes in its genome compared to broader-host-range serovars. S. enterica serovars such as S. Kentucky and S. Heidelberg also often have plasmids that may help them colonize poultry more efficiently. The ability to colonize different hosts also involves interactions with the host's immune system and commensal organisms that are present. Thus, the factors that impact the ability of Salmonella to colonize a particular host species, such as chickens, are complex and multifactorial, involving the host, the pathogen, and extrinsic pressures. It is the interplay of these factors which leads to the differences in host ranges that we observe today. PMID:24296573

Molecular and functional interactions of cat APOBEC3 and feline foamy and immunodeficiency virus proteins: different ways to counteract host-encoded restriction.

PubMed

Chareza, Sarah; Slavkovic Lukic, Dragana; Liu, Yang; Räthe, Ann-Mareen; Münk, Carsten; Zabogli, Elisa; Pistello, Mauro; Löchelt, Martin

2012-03-15

Defined host-encoded feline APOBEC3 (feA3) cytidine deaminases efficiently restrict the replication and spread of exogenous retroviruses like Feline Immunodeficiency Virus (FIV) and Feline Foamy Virus (FFV) which developed different feA3 counter-acting strategies. Here we characterize the molecular interaction of FFV proteins with the diverse feA3 proteins. The FFV accessory protein Bet is the virus-encoded defense factor which is shown here to bind all feA3 proteins independent of whether they restrict FFV, a feature shared with FIV Vif that induces degradation of all feA3s including those that do not inactivate FIV. In contrast, only some feA3 proteins bind to FFV Gag, a pattern that in part reflects the restriction pattern detected. Additionally, one-domain feA3 proteins can homo- and hetero-dimerize in vitro, but a trans-dominant phenotype of any of the low-activity feA3 forms on FFV restriction by one of the highly-active feA3Z2 proteins was not detectable. Copyright © 2012 Elsevier Inc. All rights reserved.

Interferon signaling in Peromyscus leucopus confers a potent and specific restriction to vector-borne flaviviruses.

PubMed

Izuogu, Adaeze O; McNally, Kristin L; Harris, Stephen E; Youseff, Brian H; Presloid, John B; Burlak, Christopher; Munshi-South, Jason; Best, Sonja M; Taylor, R Travis

2017-01-01

Tick-borne flaviviruses (TBFVs), including Powassan virus and tick-borne encephalitis virus cause encephalitis or hemorrhagic fevers in humans with case-fatality rates ranging from 1-30%. Despite severe disease in humans, TBFV infection of natural rodent hosts has little noticeable effect. Currently, the basis for resistance to disease is not known. We hypothesize that the coevolution of flaviviruses with their respective hosts has shaped the evolution of potent antiviral factors that suppress virus replication and protect the host from lethal infection. In the current study, we compared virus infection between reservoir host cells and related susceptible species. Infection of primary fibroblasts from the white-footed mouse (Peromyscus leucopus, a representative host) with a panel of vector-borne flaviviruses showed up to a 10,000-fold reduction in virus titer compared to control Mus musculus cells. Replication of vesicular stomatitis virus was equivalent in P. leucopus and M. musculus cells suggesting that restriction was flavivirus-specific. Step-wise comparison of the virus infection cycle revealed a significant block to viral RNA replication, but not virus entry, in P. leucopus cells. To understand the role of the type I interferon (IFN) response in virus restriction, we knocked down signal transducer and activator of transcription 1 (STAT1) or the type I IFN receptor (IFNAR1) by RNA interference. Loss of IFNAR1 or STAT1 significantly relieved the block in virus replication in P. leucopus cells. The major IFN antagonist encoded by TBFV, nonstructural protein 5, was functional in P. leucopus cells, thus ruling out ineffective viral antagonism of the host IFN response. Collectively, this work demonstrates that the IFN response of P. leucopus imparts a strong and virus-specific barrier to flavivirus replication. Future identification of the IFN-stimulated genes responsible for virus restriction specifically in P. leucopus will yield mechanistic insight into efficient control of virus replication and may inform the development of antiviral therapeutics.

Differential restriction patterns of mRNA decay factor AUF1 during picornavirus infections.

PubMed

Cathcart, Andrea L; Semler, Bert L

2014-07-01

During infection by picornaviruses, the cellular environment is modified to favour virus replication. This includes the modification of specific host proteins, including the recently discovered viral proteinase cleavage of mRNA decay factor AU-rich binding factor 1 (AUF1). This cellular RNA-binding protein was shown previously to act as a restriction factor during poliovirus, rhinovirus and coxsackievirus infection. During infection by these viruses, AUF1 relocalizes to the cytoplasm and is cleaved by the viral 3C/3CD proteinase. In this study, we demonstrated that replication of encephalomyocarditis virus (EMCV), a picornavirus belonging to the genus Cardiovirus, is AUF1 independent. During EMCV infection, AUF1 relocalized to the cytoplasm; however, unlike what is seen during enterovirus infections, AUF1 was not cleaved to detectable levels, even at late times after infection. This suggests that AUF1 does not act broadly as an inhibitor of picornavirus infections but may instead act as a selective restriction factor targeting members of the genus Enterovirus. © 2014 The Authors.

Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells.

PubMed

Zhu, Shu; Ding, Siyuan; Wang, Penghua; Wei, Zheng; Pan, Wen; Palm, Noah W; Yang, Yi; Yu, Hua; Li, Hua-Bing; Wang, Geng; Lei, Xuqiu; de Zoete, Marcel R; Zhao, Jun; Zheng, Yunjiang; Chen, Haiwei; Zhao, Yujiao; Jurado, Kellie A; Feng, Ningguo; Shan, Liang; Kluger, Yuval; Lu, Jun; Abraham, Clara; Fikrig, Erol; Greenberg, Harry B; Flavell, Richard A

2017-06-29

Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown. Here we uncover and mechanistically characterize the NLR Nlrp9b that is specifically expressed in intestinal epithelial cells and restricts rotavirus infection. Our data show that, via RNA helicase Dhx9, Nlrp9b recognizes short double-stranded RNA stretches and forms inflammasome complexes with the adaptor proteins Asc and caspase-1 to promote the maturation of interleukin (Il)-18 and gasdermin D (Gsdmd)-induced pyroptosis. Conditional depletion of Nlrp9b or other inflammasome components in the intestine in vivo resulted in enhanced susceptibility of mice to rotavirus replication. Our study highlights an important innate immune signalling pathway that functions in intestinal epithelial cells and may present useful targets in the modulation of host defences against viral pathogens.

A Paradigm for Virus–Host Coevolution: Sequential Counter-Adaptations between Endogenous and Exogenous Retroviruses

PubMed Central

Arnaud, Frederick; Caporale, Marco; Varela, Mariana; Biek, Roman; Chessa, Bernardo; Alberti, Alberto; Golder, Matthew; Mura, Manuela; Zhang, Ya-ping; Yu, Li; Pereira, Filipe; DeMartini, James C; Leymaster, Kreg; Spencer, Thomas E; Palmarini, Massimo

2007-01-01

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections of the host germline transmitted vertically from generation to generation. It is hypothesized that some ERVs are used by the host as restriction factors to block the infection of pathogenic retroviruses. Indeed, some ERVs efficiently interfere with the replication of related exogenous retroviruses. However, data suggesting that these mechanisms have influenced the coevolution of endogenous and/or exogenous retroviruses and their hosts have been more difficult to obtain. Sheep are an interesting model system to study retrovirus-host coevolution because of the coexistence in this animal species of two exogenous (i.e., horizontally transmitted) oncogenic retroviruses, Jaagsiekte sheep retrovirus and Enzootic nasal tumor virus, with highly related and biologically active endogenous retroviruses (enJSRVs). Here, we isolated and characterized the evolutionary history and molecular virology of 27 enJSRV proviruses. enJSRVs have been integrating in the host genome for the last 5–7 million y. Two enJSRV proviruses (enJS56A1 and enJSRV-20), which entered the host genome within the last 3 million y (before and during speciation within the genus Ovis), acquired in two temporally distinct events a defective Gag polyprotein resulting in a transdominant phenotype able to block late replication steps of related exogenous retroviruses. Both transdominant proviruses became fixed in the host genome before or around sheep domestication (∼ 9,000 y ago). Interestingly, a provirus escaping the transdominant enJSRVs has emerged very recently, most likely within the last 200 y. Thus, we determined sequentially distinct events during evolution that are indicative of an evolutionary antagonism between endogenous and exogenous retroviruses. This study strongly suggests that endogenization and selection of ERVs acting as restriction factors is a mechanism used by the host to fight retroviral infections. PMID:17997604

Nuclear Exclusion of the HIV-1 host defense factor APOBEC3G requires a novel cytoplasmic retention signal and is not dependent on RNA binding.

PubMed

Bennett, Ryan P; Presnyak, Vladimir; Wedekind, Joseph E; Smith, Harold C

2008-03-21

Human APOBEC3G (hA3G) is a host factor that defends against HIV-1 as well as other exogenous retroviruses and endogenous retroelements. To this end, hA3G is restricted to the cytoplasm of T lymphocytes where it interacts with viral RNA and proteins to assemble with viral particles causing a post-entry block during reverse transcription. hA3G also exhibits a mechanism to inhibit the reverse transcription of retroelements by RNA binding and sequestration into mRNA processing centers in the cytoplasm. We have determined that the molecular basis for this specialized property of hA3G is a novel cytoplasmic retention signal (CRS) that is necessary and sufficient to restrict wild-type hA3G and chimeric constructs to the cytoplasm. The CRS resides within amino acids 113-128 and is embedded within a basic flanking sequence and does not require RNA binding to retain hA3G in the cytoplasm. Paralogs of hA3G that have nuclear or cytoplasmic distributions differ from hA3G within the region encompassing the CRS motif with respect to charge and amino acid composition. We propose that the CRS enables hA3G to interact with cytoplasmic factors, and thereby enables hA3G to serve in host cell defense by restricting an antiviral sentinel to the cytoplasm. The CRS lies in a region involved in both Gag and Vif interactions; therefore, identification of this motif has important implications for the design of therapeutics that target HIV-1 while maintaining antiviral and cellular functions.

Transforming growth factor β-activated kinase 1 transcriptionally suppresses hepatitis B virus replication.

PubMed

Pang, Jinke; Zhang, Geng; Lin, Yong; Xie, Zhanglian; Liu, Hongyan; Tang, Libo; Lu, Mengji; Yan, Ran; Guo, Haitao; Sun, Jian; Hou, Jinlin; Zhang, Xiaoyong

2017-01-03

Hepatitis B Virus (HBV) replication in hepatocytes is restricted by the host innate immune system and related intracellular signaling pathways. Transforming growth factor β-activated kinase 1 (TAK1) is a key mediator of toll-like receptors and pro-inflammatory cytokine signaling pathways. Here, we report that silencing or inhibition of endogenous TAK1 in hepatoma cell lines leads to an upregulation of HBV replication, transcription, and antigen expression. In contrast, overexpression of TAK1 significantly suppresses HBV replication, while an enzymatically inactive form of TAK1 exerts no effect. By screening TAK1-associated signaling pathways with inhibitors and siRNAs, we found that the MAPK-JNK pathway was involved in TAK1-mediated HBV suppression. Moreover, TAK1 knockdown or JNK pathway inhibition induced the expression of farnesoid X receptor α, a transcription factor that upregulates HBV transcription. Finally, ectopic expression of TAK1 in a HBV hydrodynamic injection mouse model resulted in lower levels of HBV DNA and antigens in both liver and serum. In conclusion, our data suggest that TAK1 inhibits HBV primarily at viral transcription level through activation of MAPK-JNK pathway, thus TAK1 represents an intrinsic host restriction factor for HBV replication in hepatocytes.

The C-Terminal Tail of TRIM56 Dictates Antiviral Restriction of Influenza A and B Viruses by Impeding Viral RNA Synthesis

PubMed Central

Liu, Baoming; Li, Nan L.; Shen, Yang; Bao, Xiaoyong; Elbahesh, Husni; Webby, Richard J.

2016-01-01

ABSTRACT Accumulating data suggest that tripartite-motif-containing (TRIM) proteins participate in host responses to viral infections, either by acting as direct antiviral restriction factors or through regulating innate immune signaling of the host. Of >70 TRIMs, TRIM56 is a restriction factor of several positive-strand RNA viruses, including three members of the family Flaviviridae (yellow fever virus, dengue virus, and bovine viral diarrhea virus) and a human coronavirus (OC43), and this ability invariably depends upon the E3 ligase activity of TRIM56. However, the impact of TRIM56 on negative-strand RNA viruses remains unclear. Here, we show that TRIM56 puts a check on replication of influenza A and B viruses in cell culture but does not inhibit Sendai virus or human metapneumovirus, two paramyxoviruses. Interestingly, the anti-influenza virus activity was independent of the E3 ligase activity, B-box, or coiled-coil domain. Rather, deletion of a 63-residue-long C-terminal-tail portion of TRIM56 abrogated the antiviral function. Moreover, expression of this short C-terminal segment curtailed the replication of influenza viruses as effectively as that of full-length TRIM56. Mechanistically, TRIM56 was found to specifically impede intracellular influenza virus RNA synthesis. Together, these data reveal a novel antiviral activity of TRIM56 against influenza A and B viruses and provide insights into the mechanism by which TRIM56 restricts these medically important orthomyxoviruses. IMPORTANCE Options to treat influenza are limited, and drug-resistant influenza virus strains can emerge through minor genetic changes. Understanding novel virus-host interactions that alter influenza virus fitness may reveal new targets/approaches for therapeutic interventions. We show here that TRIM56, a tripartite-motif protein, is an intrinsic host restriction factor of influenza A and B viruses. Unlike its antiviral actions against positive-strand RNA viruses, the anti-influenza virus activity of TRIM56 was independent of the E3 ligase activity. Rather, expression of a short segment within the very C-terminal tail of TRIM56 inhibited the replication of influenza viruses as effectively as that of full-length TRIM56 by specifically targeting viral RNA synthesis. These data reveal the remarkable multifaceted activity of TRIM56, which has developed multiple domains to inhibit multiple viral families. They also raise the possibility of developing a broad-spectrum, TRIM56-based antiviral approach for addition to influenza prophylaxis and/or control strategies. PMID:26889027

Invasion biology in non-free-living species: interactions between abiotic (climatic) and biotic (host availability) factors in geographical space in crayfish commensals (Ostracoda, Entocytheridae)

PubMed Central

Mestre, Alexandre; Aguilar-Alberola, Josep A; Baldry, David; Balkis, Husamettin; Ellis, Adam; Gil-Delgado, Jose A; Grabow, Karsten; Klobučar, Göran; Kouba, Antonín; Maguire, Ivana; Martens, Andreas; Mülayim, Ayşegül; Rueda, Juan; Scharf, Burkhard; Soes, Menno; S Monrós, Juan; Mesquita-Joanes, Francesc

2013-01-01

In invasion processes, both abiotic and biotic factors are considered essential, but the latter are usually disregarded when modeling the potential spread of exotic species. In the framework of set theory, interactions between biotic (B), abiotic (A), and movement-related (M) factors in the geographical space can be hypothesized with BAM diagrams and tested using ecological niche models (ENMs) to estimate A and B areas. The main aim of our survey was to evaluate the interactions between abiotic (climatic) and biotic (host availability) factors in geographical space for exotic symbionts (i.e., non-free-living species), using ENM techniques combined with a BAM framework and using exotic Entocytheridae (Ostracoda) found in Europe as model organisms. We carried out an extensive survey to evaluate the distribution of entocytherids hosted by crayfish in Europe by checking 94 European localities and 12 crayfish species. Both exotic entocytherid species found, Ankylocythere sinuosa and Uncinocythere occidentalis, were widely distributed in W Europe living on the exotic crayfish species Procambarus clarkii and Pacifastacus leniusculus, respectively. No entocytherids were observed in the remaining crayfish species. The suitable area for A. sinuosa was mainly restricted by its own limitations to minimum temperatures in W and N Europe and precipitation seasonality in circum-Mediterranean areas. Uncinocythere occidentalis was mostly restricted by host availability in circum-Mediterranean regions due to limitations of P. leniusculus to higher precipitation seasonality and maximum temperatures. The combination of ENMs with set theory allows studying the invasive biology of symbionts and provides clues about biogeographic barriers due to abiotic or biotic factors limiting the expansion of the symbiont in different regions of the invasive range. The relative importance of abiotic and biotic factors on geographical space can then be assessed and applied in conservation plans. This approach can also be implemented in other systems where the target species is closely interacting with other taxa. PMID:24455152

Invasion biology in non-free-living species: interactions between abiotic (climatic) and biotic (host availability) factors in geographical space in crayfish commensals (Ostracoda, Entocytheridae).

PubMed

Mestre, Alexandre; Aguilar-Alberola, Josep A; Baldry, David; Balkis, Husamettin; Ellis, Adam; Gil-Delgado, Jose A; Grabow, Karsten; Klobučar, Göran; Kouba, Antonín; Maguire, Ivana; Martens, Andreas; Mülayim, Ayşegül; Rueda, Juan; Scharf, Burkhard; Soes, Menno; S Monrós, Juan; Mesquita-Joanes, Francesc

2013-12-01

In invasion processes, both abiotic and biotic factors are considered essential, but the latter are usually disregarded when modeling the potential spread of exotic species. In the framework of set theory, interactions between biotic (B), abiotic (A), and movement-related (M) factors in the geographical space can be hypothesized with BAM diagrams and tested using ecological niche models (ENMs) to estimate A and B areas. The main aim of our survey was to evaluate the interactions between abiotic (climatic) and biotic (host availability) factors in geographical space for exotic symbionts (i.e., non-free-living species), using ENM techniques combined with a BAM framework and using exotic Entocytheridae (Ostracoda) found in Europe as model organisms. We carried out an extensive survey to evaluate the distribution of entocytherids hosted by crayfish in Europe by checking 94 European localities and 12 crayfish species. Both exotic entocytherid species found, Ankylocythere sinuosa and Uncinocythere occidentalis, were widely distributed in W Europe living on the exotic crayfish species Procambarus clarkii and Pacifastacus leniusculus, respectively. No entocytherids were observed in the remaining crayfish species. The suitable area for A. sinuosa was mainly restricted by its own limitations to minimum temperatures in W and N Europe and precipitation seasonality in circum-Mediterranean areas. Uncinocythere occidentalis was mostly restricted by host availability in circum-Mediterranean regions due to limitations of P. leniusculus to higher precipitation seasonality and maximum temperatures. The combination of ENMs with set theory allows studying the invasive biology of symbionts and provides clues about biogeographic barriers due to abiotic or biotic factors limiting the expansion of the symbiont in different regions of the invasive range. The relative importance of abiotic and biotic factors on geographical space can then be assessed and applied in conservation plans. This approach can also be implemented in other systems where the target species is closely interacting with other taxa.

Conjugation in Escherichia coli

PubMed Central

Boyer, Herbert

1966-01-01

Boyer, Herbert (Yale University, New Haven, Conn.). Conjugation in Escherichia coli. J. Bacteriol. 91:1767–1772. 1966.—The sex factor of Escherichia coli K-12 was introduced into an E. coli B/r strain by circumventing the host-controlled modification and restriction incompatibilities known to exist between these closely related strains. The sexual properties of the constructed F+ B strain and its Hfr derivatives were examined. These studies showed that the E. coli strain B/r F+ and Hfr derivatives are similar to the E. coli strain K-12 F+ and Hfr derivatives. However, the site of sex factor integration was found to be dependent on the host genome. PMID:5327905

Ecological fitness and strategies of adaptation of Bartonella species to their hosts and vectors☆

PubMed Central

Chomel, Bruno B.; Boulouis, Henri-Jean; Breitschwerdt, Edward B.; Kasten, Rickie W.; Vayssier-Taussat, Muriel; Birtles, Richard J.; Koehler, Jane E.; Dehio, Christoph

2009-01-01

Bartonella spp. are facultative intracellular bacteria that cause characteristic host-restricted hemotropic infections in mammals and are typically transmitted by blood-sucking arthropods. In the mammalian reservoir, these bacteria initially infect a yet unrecognized primary niche, which seeds organisms into the blood stream leading to the establishment of a long-lasting intra-erythrocytic bacteremia as the hall-mark of infection. Bacterial type IV secretion systems, which are supra-molecular transporters ancestrally related to bacterial conjugation systems, represent crucial pathogenicity factors that have contributed to a radial expansion of the Bartonella lineage in nature by facilitating adaptation to unique mammalian hosts. On the molecular level, the type IV secretion system VirB/VirD4 is known to translocate a cocktail of different effector proteins into host cells, which subvert multiple cellular functions to the benefit of the infecting pathogen. Furthermore, bacterial adhesins mediate a critical, early step in the pathogenesis of the bartonellae by binding to extracellular matrix components of host cells, which leads to firm bacterial adhesion to the cell surface as a prerequisite for the efficient translocation of type IV secretion effector proteins. The best-studied adhesins in bartonellae are the orthologous trimeric autotransporter adhesins, BadA in Bartonella henselae and the Vomp family in Bartonella quintana. Genetic diversity and strain variability also appear to enhance the ability of bartonellae to invade not only specific reservoir hosts, but also accidental hosts, as shown for B. henselae. Bartonellae have been identified in many different blood-sucking arthropods, in which they are typically found to cause extracellular infections of the mid-gut epithelium. Adaptation to specific vectors and reservoirs seems to be a common strategy of bartonellae for transmission and host diversity. However, knowledge regarding arthropod specificity/restriction, the mode of transmission, and the bacterial factors involved in arthropod infection and transmission is still limited. PMID:19284965

Capsid-binding retrovirus restriction factors: discovery, restriction specificity and implications for the development of novel therapeutics.

PubMed

Sanz-Ramos, Marta; Stoye, Jonathan P

2013-12-01

The development of drugs against human immunodeficiency virus type 1 infection has been highly successful, and numerous combinational treatments are currently available. However, the risk of the emergence of resistance and the toxic effects associated with prolonged use of antiretroviral therapies have emphasized the need to consider alternative approaches. One possible area of investigation is provided by the properties of restriction factors, cellular proteins that protect organisms against retroviral infection. Many show potent viral inhibition. Here, we describe the discovery, properties and possible therapeutic uses of the group of restriction factors known to interact with the capsid core of incoming retroviruses. This group comprises Fv1, TRIM5α and TRIMCypA: proteins that all act shortly after virus entry into the target cell and block virus replication at different stages prior to integration of viral DNA into the host chromosome. They have different origins and specificities, but share general structural features required for restriction, with an N-terminal multimerization domain and a C-terminal capsid-binding domain. Their overall efficacy makes it reasonable to ask whether they might provide a framework for developing novel antiretroviral strategies.

Extending the Host Range of Bacteriophage Particles for DNA Transduction.

PubMed

Yosef, Ido; Goren, Moran G; Globus, Rea; Molshanski-Mor, Shahar; Qimron, Udi

2017-06-01

A major limitation in using bacteriophage-based applications is their narrow host range. Approaches for extending the host range have focused primarily on lytic phages in hosts supporting their propagation rather than approaches for extending the ability of DNA transduction into phage-restrictive hosts. To extend the host range of T7 phage for DNA transduction, we have designed hybrid particles displaying various phage tail/tail fiber proteins. These modular particles were programmed to package and transduce DNA into hosts that restrict T7 phage propagation. We have also developed an innovative generalizable platform that considerably enhances DNA transfer into new hosts by artificially selecting tails that efficiently transduce DNA. In addition, we have demonstrated that the hybrid particles transduce desired DNA into desired hosts. This study thus critically extends and improves the ability of the particles to transduce DNA into novel phage-restrictive hosts, providing a platform for myriad applications that require this ability. Copyright © 2017 Elsevier Inc. All rights reserved.

Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells

PubMed Central

Zhu, Shu; Ding, Siyuan; Wang, Penghua; Wei, Zheng; Pan, Wen; Palm, Noah W; Yang, Yi; Yu, Hua; Li, Hua-Bing; Wang, Geng; Lei, Xuqiu; de Zoete, Marcel R.; Zhao, Jun; Zheng, Yunjiang; Chen, Haiwei; Zhao, Yujiao; Jurado, Kellie A.; Feng, Ningguo; Shan, Liang; Kluger, Yuval; Lu, Jun; Abraham, Clara; Fikrig, Erol; Greenberg, Harry B.; Flavell, Richard A.

2018-01-01

Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide1. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling2–5, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown. Here we uncover and mechanistically characterize the NLR Nlrp9b that is specifically expressed in intestinal epithelial cells and restricts rotavirus infection. Our data show that, via RNA helicase Dhx9, Nlrp9b recognizes short double-stranded RNA stretches and forms inflammasome complexes with the adaptor proteins Asc and caspase-1 to promote the maturation of interleukin (Il)-18 and gasdermin D (Gsdmd)-induced pyroptosis. Conditional depletion of Nlrp9b or other inflammasome components in the intestine in vivo resulted in enhanced susceptibility of mice to rotavirus replication. Our study highlights an important innate immune signalling pathway that functions in intestinal epithelial cells and may present useful targets in the modulation of host defences against viral pathogens. PMID:28636595

The Yersinia Virulence Factor YopM Hijacks Host Kinases to Inhibit Type III Effector-Triggered Activation of the Pyrin Inflammasome.

PubMed

Chung, Lawton K; Park, Yong Hwan; Zheng, Yueting; Brodsky, Igor E; Hearing, Patrick; Kastner, Daniel L; Chae, Jae Jin; Bliska, James B

2016-09-14

Pathogenic Yersinia, including Y. pestis, the agent of plague in humans, and Y. pseudotuberculosis, the related enteric pathogen, deliver virulence effectors into host cells via a prototypical type III secretion system to promote pathogenesis. These effectors, termed Yersinia outer proteins (Yops), modulate multiple host signaling responses. Studies in Y. pestis and Y. pseudotuberculosis have shown that YopM suppresses infection-induced inflammasome activation; however, the underlying molecular mechanism is largely unknown. Here we show that YopM specifically restricts the pyrin inflammasome, which is triggered by the RhoA-inactivating enzymatic activities of YopE and YopT, in Y. pseudotuberculosis-infected macrophages. The attenuation of a yopM mutant is fully reversed in pyrin knockout mice, demonstrating that YopM inhibits pyrin to promote virulence. Mechanistically, YopM recruits and activates the host kinases PRK1 and PRK2 to negatively regulate pyrin by phosphorylation. These results show how a virulence factor can hijack host kinases to inhibit effector-triggered pyrin inflammasome activation. Copyright © 2016 Elsevier Inc. All rights reserved.

Restrictions to cross species transmission of lentiviral infection gleaned from studies of FIV

PubMed Central

Troyer, Jennifer; Poss, Mary

2009-01-01

More than 40 species of primates and over 20 species of cats harbor antibodies that sero-react to lentiviral antigens. In nearly all cases where viral genetic analysis has been conducted, each host species is infected with a unique lentivirus. Though lentivirus clades within a species can be substantially divergent, they are typically monophyletic within that species. A notable significant departure from this observation is apparent cross-species transmission of FIV between bobcats (Lynx rufus) and pumas (Puma concolor) in southern California that has occurred at least three times; evidence from one bobcat sequence suggests this cross-over may have also occurred in Florida between bobcats and the endangered Florida panther. Several other isolated reports demonstrate cross-species transmission of FIV isolates among captive animals housed in close proximity, and it is well established that HIV-1 and HIV-2 arose from human contact with SIV-infected nonhuman primates. Using an experimental model, we have determined that domestic cats (Felis catus) are susceptible to FIVs originating from pumas or lions. While infections are initially replicative, and animals seroconvert, within a relatively short period of time circulating virus is reduced to nearly undetectable levels in a majority of animals. This diminution of viral load is proportional to initial viral peak. Although viral reservoirs can be identified in gastrointestinal tissues, most viral genomes recovered peripherally are highly mutated, suggesting that the non-adapted host successfully inhibits normal viral replication, leading to replication incompetent viral progeny. Mechanisms possible for such restriction of cross-species infections in natural settings include: 1. Lack of contact conducive to lentiviral transmission between infected and shedding animals of different species; 2. Lack of suitable receptor repertoire to allow viral entry to susceptible cells of a new species; 3. Cellular machinery in the new host sufficiently divergent from the primary host to support viral replication (ie passive unfacilitated viral replication); 4. Intracellular restriction mechanisms present in the new host that is able to limit viral replication (i.e. active interrupted viral replication. These include factors that limit uncoating, replication, packaging, and virion release); 5. Unique ability of new host to raise sterilizing adaptive immunity, resulting in aborted infection and inability to spread infections among con-specifics; or, 6. Production of defective or non-infectious viral progeny that lack cellular cofactors to render them infectious to conspecifics (i.e. particles lacking appropriate cellular components in viral Env to render them infectious to other animals of the same species). Data to support or refute the relative importance of each of these possibilities is described in this review. Insights based on our in vivo cross-species model suggest intracellular restriction mechanisms effectively inhibit rapid inter-specific transmission of lentiviruses. Further, limited contact both within and between species in natural populations is highly relevant to limiting the opportunity for spread of FIV strains. Studies of naturally-occurring SIV and innate host restriction systems suggest these same two mechanisms are significant factors inhibiting widespread cross-species transmission of lentiviruses among primate species as well. PMID:19896218

SAMHD1 knockout mice: modeling retrovirus restriction in vivo.

PubMed

Wu, Li

2013-11-20

The host dNTP hydrolase SAMHD1 acts as a viral restriction factor to inhibit the replication of several retroviruses and DNA viruses in non-cycling human immune cells. However, understanding the physiological role of mammalian SAMHD1 has been elusive due to the lack of an animal model. Two recent studies reported the generation of samhd1 knockout mouse models for investigating the restriction of HIV-1 vectors and endogenous retroviruses in vivo. Both studies suggest that SAMHD1 is important for regulating the intracellular dNTP pool and the intrinsic immunity against retroviral infection, despite different outcomes of HIV-1 vector transduction in these mouse models. Here I discuss the significance of these new findings and the future directions in studying SAMHD1-mediated retroviral restriction.

One Health and Food-Borne Disease: Salmonella Transmission between Humans, Animals, and Plants.

PubMed

Silva, Claudia; Calva, Edmundo; Maloy, Stanley

2014-02-01

There are >2,600 recognized serovars of Salmonella enterica. Many of these Salmonella serovars have a broad host range and can infect a wide variety of animals, including mammals, birds, reptiles, amphibians, fish, and insects. In addition, Salmonella can grow in plants and can survive in protozoa, soil, and water. Hence, broad-host-range Salmonella can be transmitted via feces from wild animals, farm animals, and pets or by consumption of a wide variety of common foods: poultry, beef, pork, eggs, milk, fruit, vegetables, spices, and nuts. Broad-host-range Salmonella pathogens typically cause gastroenteritis in humans. Some Salmonella serovars have a more restricted host range that is associated with changes in the virulence plasmid pSV, accumulation of pseudogenes, and chromosome rearrangements. These changes in host-restricted Salmonella alter pathogen-host interactions such that host-restricted Salmonella organisms commonly cause systemic infections and are transmitted between host populations by asymptomatic carriers. The secondary consequences of efforts to eliminate host-restricted Salmonella serovars demonstrate that basic ecological principles govern the environmental niches occupied by these pathogens, making it impossible to thwart Salmonella infections without a clear understanding of the human, animal, and environmental reservoirs of these pathogens. Thus, transmission of S. enterica provides a compelling example of the One Health paradigm because reducing human infections will require the reduction of Salmonella in animals and limitation of transmission from the environment.

TIA-1 and TIAR interact with 5'-UTR of enterovirus 71 genome and facilitate viral replication.

PubMed

Wang, Xiaohui; Wang, Huanru; Li, Yixuan; Jin, Yu; Chu, Ying; Su, Airong; Wu, Zhiwei

2015-10-16

Enterovirus 71 is one of the major causative pathogens of HFMD in children. Upon infection, the viral RNA is translated in an IRES-dependent manner and requires several host factors for effective replication. Here, we found that T-cell-restricted intracellular antigen 1 (TIA-1), and TIA-1 related protein (TIAR) were translocated from nucleus to cytoplasm after EV71 infection and localized to the sites of viral replication. We found that TIA-1 and TIAR can facilitate EV71 replication by enhancing the viral genome synthesis in host cells. We demonstrated that both proteins bound to the stem-loop I of 5'-UTR of viral genome and improved the stability of viral genomic RNA. Our results suggest that TIA-1 and TIAR are two new host factors that interact with 5-UTR of EV71 genome and positively regulate viral replication. Copyright © 2015 Elsevier Inc. All rights reserved.

Interplay between Herpesvirus Infection and Host Defense by PML Nuclear Bodies.

PubMed

Tavalai, Nina; Stamminger, Thomas

2009-12-01

In recent studies we and others have identified the cellular proteins PML, hDaxx, and Sp100, which form a subnuclear structure known as nuclear domain 10 (ND10) or PML nuclear bodies (PML-NBs), as host restriction factors that counteract herpesviral infections by inhibiting viral replication at different stages. The antiviral function of ND10, however, is antagonized by viral regulatory proteins (e.g., ICP0 of herpes simplex virus; IE1 of human cytomegalovirus) which induce either a modification or disruption of ND10. This review will summarize the current knowledge on how viral replication is inhibited by ND10 proteins. Furthermore, herpesviral strategies to defeat this host defense mechanism are discussed.

Co-expression of HLA-B7 and HLA-B27 alleles is associated with B7-restricted immunodominant responses following influenza infection.

PubMed

Akram, Ali; Inman, Robert D

2013-12-01

It is recognized that host response following viral infection is characterized by immunodominance, but deciphering the different factors contributing to immunodominance has proved a challenge due to concurrent expression of multiple MHC class I alleles. To address this, we generated H2-K(-/-)/D(-/-) double-knockout transgenic mice expressing either one or two human MHC-I alleles. We hypothesized that co-expression of different allele combinations figures critically in immunodominance and examined this in influenza-infected, double Tg MHC-I mice. In A2/B7 or A2/B27 mice, using ELISpot assays with the A2-restricted matrix I.58-66, the B7-restricted NP418-426 or the B27-restricted NP383-391 influenza A (flu) epitopes, we observed the expected recognition of both peptides for both alleles. In contrast, in flu-infected B7/B27 mice, a significantly reduced level of B27/NP383-restricted CTL response was detected while there was no change in the B7/NP418-restricted CTL response. Flu-specific tetramer studies revealed a partial deletion of Vβ8.1(+) NP383/B27-restricted CD8(+) T cells, and a diminished Vβ12(+) CD8(+) T-cell expansion in B7/B27 Tg mice. Using HLA Tg chimeric mice, we confirmed these findings. These findings shed light on the immune consequences of co-dominant expression of MHC-I alleles for host immune response to pathogens. © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Sp100 isoform-specific regulation of human adenovirus 5 gene expression.

PubMed

Berscheminski, Julia; Wimmer, Peter; Brun, Juliane; Ip, Wing Hang; Groitl, Peter; Horlacher, Tim; Jaffray, Ellis; Hay, Ron T; Dobner, Thomas; Schreiner, Sabrina

2014-06-01

Promyelocytic leukemia nuclear bodies (PML-NBs) are nuclear structures that accumulate intrinsic host factors to restrict viral infections. To ensure viral replication, these must be limited by expression of viral early regulatory proteins that functionally inhibit PML-NB-associated antiviral effects. To benefit from the activating capabilities of Sp100A and simultaneously limit repression by Sp100B, -C, and -HMG, adenoviruses (Ads) employ several features to selectively and individually target these isoforms. Ads induce relocalization of Sp100B, -C, and -HMG from PML-NBs prior to association with viral replication centers. In contrast, Sp100A is kept at the PML tracks that surround the newly formed viral replication centers as designated sites of active transcription. We concluded that the host restriction factors Sp100B, -C, and -HMG are potentially inactivated by active displacement from these sites, whereas Sp100A is retained to amplify Ad gene expression. Ad-dependent loss of Sp100 SUMOylation is another crucial part of the virus repertoire to counteract intrinsic immunity by circumventing Sp100 association with HP1, therefore limiting chromatin condensation. We provide evidence that Ad selectively counteracts antiviral responses and, at the same time, benefits from PML-NB-associated components which support viral gene expression by actively recruiting them to PML track-like structures. Our findings provide insights into novel strategies for manipulating transcriptional regulation to either inactivate or amplify viral gene expression. We describe an adenoviral evasion strategy that involves isoform-specific and active manipulation of the PML-associated restriction factor Sp100. Recently, we reported that the adenoviral transactivator E1A targets PML-II to efficiently activate viral transcription. In contrast, the PML-associated proteins Daxx and ATRX are inhibited by early viral factors. We show that this concept is more intricate and significant than originally believed, since adenoviruses apparently take advantage of specific PML-NB-associated proteins and simultaneously inhibit antiviral measures to maintain the viral infectious program. Specifically, we observed Ad-induced relocalization of the Sp100 isoforms B, C, and HMG from PML-NBs juxtaposed with viral replication centers. In contrast, Sp100A is retained at Ad-induced PML tracks that surround the newly formed viral replication centers, acting as designated sites of active transcription. The host restriction factors Sp100B, -C, and -HMG are potentially inactivated by active displacement from these sites, whereas Sp100A is retained to amplify Ad gene expression.

Host Range Factor 1 from Lymantria dispar Nucleopolyhedrovirus (NPV) Is an Essential Viral Factor Required for Productive Infection of NPVs in IPLB-Ld652Y Cells Derived from L. dispar

PubMed Central

Ishikawa, Hiroki; Ikeda, Motoko; Felipe Alves, Cristiano A.; Thiem, Suzanne M.; Kobayashi, Michihiro

2004-01-01

Host range factor 1 (HRF-1) of Lymantria dispar multinucleocapsid nucleopolyhedrovirus promotes Autographa californica MNPV replication in nonpermissive Ld652Y cells derived from L. dispar. Here we demonstrate that restricted Hyphantria cunea NPV replication in Ld652Y cells was not due to apoptosis but was likely due to global protein synthesis arrest that could be restored by HRF-1. Our data also showed that HRF-1 promoted the production of progeny virions for two other baculoviruses, Bombyx mori NPV and Spodoptera exigua MNPV, whose replication in Ld652Y cells is limited to replication of viral DNA without successful production of infectious progeny virions. Thus, HRF-1 is an essential viral factor required for productive infection of NPVs in Ld652Y cells. PMID:15507661

Host range factor 1 from Lymantria dispar Nucleopolyhedrovirus (NPV) is an essential viral factor required for productive infection of NPVs in IPLB-Ld652Y cells derived from L. dispar.

PubMed

Ishikawa, Hiroki; Ikeda, Motoko; Alves, Cristiano A Felipe; Thiem, Suzanne M; Kobayashi, Michihiro

2004-11-01

Host range factor 1 (HRF-1) of Lymantria dispar multinucleocapsid nucleopolyhedrovirus promotes Autographa californica MNPV replication in nonpermissive Ld652Y cells derived from L. dispar. Here we demonstrate that restricted Hyphantria cunea NPV replication in Ld652Y cells was not due to apoptosis but was likely due to global protein synthesis arrest that could be restored by HRF-1. Our data also showed that HRF-1 promoted the production of progeny virions for two other baculoviruses, Bombyx mori NPV and Spodoptera exigua MNPV, whose replication in Ld652Y cells is limited to replication of viral DNA without successful production of infectious progeny virions. Thus, HRF-1 is an essential viral factor required for productive infection of NPVs in Ld652Y cells.

Host generalists and specialists emerging side by side: an analysis of evolutionary patterns in the cosmopolitan chewing louse genus Menacanthus.

PubMed

Martinů, Jana; Sychra, Oldřich; Literák, Ivan; Čapek, Miroslav; Gustafsson, Daniel L; Štefka, Jan

2015-01-01

Parasites with wide host spectra provide opportunities to study the ecological parameters of speciation, as well as the process of the evolution of host specificity. The speciose and cosmopolitan louse genus Menacanthus comprises both multi-host and specialised species, allowing exploration of the ecological and historical factors affecting the evolution of parasites using a comparative approach. We used phylogenetic analysis to reconstruct evolutionary relationships in 14 species of Menacanthus based on the sequences of one mitochondrial and one nuclear gene. The results allowed us to validate species identification based on morphology, as well as to explore host distribution by assumed generalist and specialist species. Our analyses confirmed a narrow host use for several species, however in some cases, the supposed host specialists had a wider host spectrum than anticipated. In one case a host generalist (Menacanthus eurysternus) was clustered terminally on a clade almost exclusively containing host specialists. Such a clade topology indicates that the process of host specialisation may not be irreversible in parasite evolution. Finally, we compared patterns of population genetic structure, geographic distribution and host spectra between two selected species, M. eurysternus and Menacanthus camelinus, using haplotype networks. Menacanthus camelinus showed limited geographical distribution in combination with monoxenous host use, whereas M. eurysternus showed a global distribution and lack of host specificity. It is suggested that frequent host switching maintains gene flow between M. eurysternus populations on unrelated hosts in local populations. However, gene flow between geographically distant localities was restricted, suggesting that geography rather than host-specificity is the main factor defining the global genetic diversity of M. eurysternus. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Hepatitis C virus and antiviral innate immunity: who wins at tug-of-war?

PubMed

Yang, Da-Rong; Zhu, Hai-Zhen

2015-04-07

Hepatitis C virus (HCV) is a major human pathogen of chronic hepatitis and related liver diseases. Innate immunity is the first line of defense against invading foreign pathogens, and its activation is dependent on the recognition of these pathogens by several key sensors. The interferon (IFN) system plays an essential role in the restriction of HCV infection via the induction of hundreds of IFN-stimulated genes (ISGs) that inhibit viral replication and spread. However, numerous factors that trigger immune dysregulation, including viral factors and host genetic factors, can help HCV to escape host immune response, facilitating viral persistence. In this review, we aim to summarize recent advances in understanding the innate immune response to HCV infection and the mechanisms of ISGs to suppress viral survival, as well as the immune evasion strategies for chronic HCV infection.

Interferon in lyssavirus infection.

PubMed

Rieder, Martina; Finke, Stefan; Conzelmann, Karl-Klaus

2012-01-01

Rabies is a zoonosis still claiming more than 50 000 human deaths per year. Typically, human cases are due to infection with rabies virus, the prototype of the Lyssavirus genus, but sporadic cases of rabies-like encephalitis caused by other lyssaviruses have been reported. In contrast to rabies virus, which has an extremely broad host range including many terrestrial warm-blooded animals, rabies-related viruses are associated predominantly with bats and rarely infect terrestrial species. In spite of a very close genetic relationship of rabies and rabies-related viruses, the factors determining the limited host range of rabies-related viruses are not clear. In the past years the importance of viral countermeasures against the host type I interferon system for establishment of an infection became evident. The rabies virus phosphoprotein (P) has emerged as a critical factor required for paralysing the signalling cascades leading to transcriptional activation of interferon genes as well as interferon signalling pathways, thereby limiting expression of antiviral and immune stimulatory genes. Comparative studies would be of interest in order to determine whether differential abilities of the lyssavirus P proteins contribute to the restricted host range of lyssaviruses.

Remodeling of the Host Cell Plasma Membrane by HIV-1 Nef and Vpu: A Strategy to Ensure Viral Fitness and Persistence.

PubMed

Sugden, Scott M; Bego, Mariana G; Pham, Tram N Q; Cohen, Éric A

2016-03-03

The plasma membrane protects the cell from its surroundings and regulates cellular communication, homing, and metabolism. Not surprisingly, the composition of this membrane is highly controlled through the vesicular trafficking of proteins to and from the cell surface. As intracellular pathogens, most viruses exploit the host plasma membrane to promote viral replication while avoiding immune detection. This is particularly true for the enveloped human immunodeficiency virus (HIV), which assembles and obtains its lipid shell directly at the plasma membrane. HIV-1 encodes two proteins, negative factor (Nef) and viral protein U (Vpu), which function primarily by altering the quantity and localization of cell surface molecules to increase virus fitness despite host antiviral immune responses. These proteins are expressed at different stages in the HIV-1 life cycle and employ a variety of mechanisms to target both unique and redundant surface proteins, including the viral receptor CD4, host restriction factors, immunoreceptors, homing molecules, tetraspanins and membrane transporters. In this review, we discuss recent progress in the study of the Nef and Vpu targeting of host membrane proteins with an emphasis on how remodeling of the cell membrane allows HIV-1 to avoid host antiviral immune responses leading to the establishment of systemic and persistent infection.

Potent and reversible lentiviral vector restriction in murine induced pluripotent stem cells.

PubMed

Geis, Franziska K; Galla, Melanie; Hoffmann, Dirk; Kuehle, Johannes; Zychlinski, Daniela; Maetzig, Tobias; Schott, Juliane W; Schwarzer, Adrian; Goffinet, Christine; Goff, Stephen P; Schambach, Axel

2017-05-31

Retroviral vectors are derived from wild-type retroviruses, can be used to study retrovirus-host interactions and are effective tools in gene and cell therapy. However, numerous cell types are resistant or less permissive to retrovirus infection due to the presence of active defense mechanisms, or the absence of important cellular host co-factors. In contrast to multipotent stem cells, pluripotent stem cells (PSC) have potential to differentiate into all three germ layers. Much remains to be elucidated in the field of anti-viral immunity in stem cells, especially in PSC. In this study, we report that transduction with HIV-1-based, lentiviral vectors (LV) is impaired in murine PSC. Analyses of early retroviral events in induced pluripotent stem cells (iPSC) revealed that the restriction is independent of envelope choice and does not affect reverse transcription, but perturbs nuclear entry and proviral integration. Proteasomal inhibition by MG132 could not circumvent the restriction. However, prevention of cyclophilin A (CypA) binding to the HIV-1 capsid via use of either a CypA inhibitor (cyclosporine A) or CypA-independent capsid mutants improved transduction. In addition, application of higher vector doses also increased transduction. Our data revealed a CypA mediated restriction in iPSC, which was acquired during reprogramming, associated with pluripotency and relieved upon subsequent differentiation. We showed that murine PSC and iPSC are less susceptible to LV. The block observed in iPSC was CypA-dependent and resulted in reduced nuclear entry of viral DNA and proviral integration. Our study helps to improve transduction of murine pluripotent cells with HIV-1-based vectors and contributes to our understanding of retrovirus-host interactions in PSC.

Structural, functional and evolutionary relationships between homing endonucleases and proteins from their host organisms

PubMed Central

Taylor, Gregory K.; Stoddard, Barry L.

2012-01-01

Homing endonucleases (HEs) are highly specific DNA-cleaving enzymes that are encoded by invasive DNA elements (usually mobile introns or inteins) within the genomes of phage, bacteria, archea, protista and eukaryotic organelles. Six unique structural HE families, that collectively span four distinct nuclease catalytic motifs, have been characterized to date. Members of each family display structural homology and functional relationships to a wide variety of proteins from various organisms. The biological functions of those proteins are highly disparate and include non-specific DNA-degradation enzymes, restriction endonucleases, DNA-repair enzymes, resolvases, intron splicing factors and transcription factors. These relationships suggest that modern day HEs share common ancestors with proteins involved in genome fidelity, maintenance and gene expression. This review summarizes the results of structural studies of HEs and corresponding proteins from host organisms that have illustrated the manner in which these factors are related. PMID:22406833

IRES-mediated translation of foot-and-mouth disease virus (FMDV) in cultured cells derived from FMDV-susceptible and -insusceptible animals.

PubMed

Kanda, Takehiro; Ozawa, Makoto; Tsukiyama-Kohara, Kyoko

2016-03-31

Foot-and-mouth disease virus (FMDV) possess a positive sense, single stranded RNA genome. Internal ribosomal entry site (IRES) element exists within its 5' untranslated region (5'UTR) of the viral RNA. Translation of the viral RNA is initiated by internal entry of the 40S ribosome within the IRES element. This process is facilitated by cellular factors known as IRES trans-acting factors (ITAFs). Foot-and-mouth disease (FMD) is host-restricted disease for cloven-hoofed animals such as cattle and pigs, but the factors determining the host range have not been identified yet. Although, ITAFs are known to promote IRES-mediated translation, these findings were confirmed only in cells derived from FMDV-insusceptible animals so far. We evaluated and compared the IRES-mediated translation activities among cell lines derived from four different animal species using bicistronic luciferase reporter plasmid, which possesses an FMDV-IRES element between Renilla and Firefly luciferase genes. Furthermore, we analyzed the effect of the cellular factors on IRES-mediated translation by silencing the cellular factors using siRNA in both FMDV-susceptible and -insusceptible animal cells. Our data indicated that IRES-mediated translational activity was not linked to FMDV host range. ITAF45 promoted IRES-mediated translation in all cell lines, and the effects of poly-pyrimidine tract binding protein (PTB) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) were observed only in FMDV-susceptible cells. Thus, PTB and 4E-BP1 may influence the host range of FMDV. IRES-mediated translation activity of FMDV was not predictive of its host range. ITAF45 promoted IRES-mediated translation in all cells, and the effects of PTB and 4E-BP1 were observed only in FMDV-susceptible cells.

TRIM41-Mediated Ubiquitination of Nucleoprotein Limits Influenza A Virus Infection.

PubMed

Patil, Girish; Zhao, Mengmeng; Song, Kun; Hao, Wenzhuo; Bouchereau, Daniel; Wang, Lingyan; Li, Shitao

2018-06-13

Influenza A virus (IAV) is a highly transmissible respiratory pathogen and a major cause of morbidity and mortality around the world. Nucleoprotein (NP) is an abundant IAV protein essential for multiple steps of viral life cycle. Our recent proteomic study of the IAV-host interaction network found that the tripartite motif containing 41 (TRIM41), a ubiquitin E3 ligase, interacted with NP. However, the role of TRIM41 in IAV infection is unknown. Here, we report that TRIM41 interacts with NP through its SPRY domain. Furthermore, TRIM41 is constitutively expressed in lung epithelial cells and overexpression of TRIM41 inhibits IAV infection. Conversely, RNA interference (RNAi) and knockout of TRIM41 increase host susceptibility to IAV infection. As a ubiquitin E3 ligase, TRIM41 ubiquitinates NP in vitro and in cells. The TRIM41 mutant lacking E3 ligase activity fails to inhibit IAV infection, suggesting that the E3 ligase activity is indispensable for TRIM41 antiviral function. Mechanistic analysis further revealed that the polyubiquitination leads to NP protein degradation and viral inhibition. Taken together, TRIM41 is a constitutively expressed intrinsic IAV restriction factor that targets NP for ubiquitination and protein degradation. IMPORTANCE Influenza control strategies rely on annual immunization and require frequent updates of the vaccine, which are not always a foolproof process. Furthermore, the current antivirals are also losing effectiveness as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new antiviral mechanisms and develop therapeutic drugs based on these mechanisms. Targeting the virus-host interface is an emerging new strategy because host factors controlling viral replication activity will be ideal candidates and cellular proteins are less likely to mutate under drug-mediated selective pressure. Here, we show that the ubiquitin E3 ligase TRIM41 is an intrinsic host restriction factor to IAV. TRIM41 directly binds the viral nucleoprotein and targets it for ubiquitination and proteasomal degradation, thereby limiting viral infection. Exploitation of this natural defense pathway may open new avenues to develop influenza antivirals. Copyright © 2018 American Society for Microbiology.

Viral Mimicry to Usurp Ubiquitin and SUMO Host Pathways

PubMed Central

Wimmer, Peter; Schreiner, Sabrina

2015-01-01

Posttranslational modifications (PTMs) of proteins include enzymatic changes by covalent addition of cellular regulatory determinants such as ubiquitin (Ub) and small ubiquitin-like modifier (SUMO) moieties. These modifications are widely used by eukaryotic cells to control the functional repertoire of proteins. Over the last decade, it became apparent that the repertoire of ubiquitiylation and SUMOylation regulating various biological functions is not restricted to eukaryotic cells, but is also a feature of human virus families, used to extensively exploit complex host-cell networks and homeostasis. Intriguingly, besides binding to host SUMO/Ub control proteins and interfering with the respective enzymatic cascade, many viral proteins mimic key regulatory factors to usurp this host machinery and promote efficient viral outcomes. Advanced detection methods and functional studies of ubiquitiylation and SUMOylation during virus-host interplay have revealed that human viruses have evolved a large arsenal of strategies to exploit these specific PTM processes. In this review, we highlight the known viral analogs orchestrating ubiquitin and SUMO conjugation events to subvert and utilize basic enzymatic pathways. PMID:26343706

SIRT3 restricts HBV transcription and replication via epigenetic regulation of cccDNA involving SUV39H1 and SETD1A histone methyltransferases.

PubMed

Ren, Ji-Hua; Hu, Jie-Li; Cheng, Sheng-Tao; Yu, Hai-Bo; Wong, Vincent Kam Wai; Law, Betty Yuen Kwan; Yang, Yong-Feng; Huang, Ying; Liu, Yi; Chen, Wei-Xian; Cai, Xue-Fei; Tang, Hua; Hu, Yuan; Zhang, Wen-Lu; Liu, Xiang; Long, Quan-Xin; Zhou, Li; Tao, Na-Na; Zhou, Hong-Zhong; Yang, Qiu-Xia; Ren, Fang; He, Lin; Gong, Rui; Huang, Ai-Long; Chen, Juan

2018-04-06

Hepatitis B virus (HBV) infection remains a major health problem worldwide. Maintenance of the covalently closed circular DNA (cccDNA) which serves as a template for HBV RNA transcription is responsible for the failure of eradicating chronic HBV during current antiviral therapy. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications. In this study, we identified SIRT3 as a host factor restricting HBV transcription and replication by screening seven members of Sirtuin family which is the class III histone deacetylase. Ectopic SIRT3 expression significantly reduced total HBV RNAs, 3.5-kb RNA as well as replicative intermediate DNA in HBV-infected HepG2-NTCP cells and PHH. In contrast, gene silencing of SIRT3 promoted HBV transcription and replication. Mechanistic study found nuclear SIRT3 was recruited to the HBV cccDNA, where it deacetylated histone 3 lysine 9 (H3K9). Importantly, occupancy of SIRT3 onto cccDNA could increase the recruitment of histone methyltransferase SUV39H1 to cccDNA and decrease recruitment of SETD1A, leading to a marked increase of H3K9me3 and a decrease of H3K4me3 on cccDNA. Moreover, SIRT3-mediated HBV cccDNA transcriptional repression involved decreased binding of host RNA polymerase II and transcription factor YY1 to cccDNA. Finally, viral protein HBx could relieve SIRT3-mediated cccDNA transcriptional repression by inhibiting both SIRT3 expression and its recruitment to cccDNA. SIRT3 is a novel host factor epigenetically restricting HBV cccDNA transcription by acting cooperatively with histone methyltransferase. These data provided a rational for the use of SIRT3 activators in the prevention or treatment of HBV infection. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

7 CFR 301.92-4 - Conditions governing the interstate movement of regulated, restricted, and associated articles...

Code of Federal Regulations, 2010 CFR

2010-01-01

... regulated, restricted, and associated articles, and non-host nursery stock from quarantined and regulated... associated articles, and non-host nursery stock from quarantined and regulated areas. (a) Interstate movement... movement of nursery stock from nurseries in quarantined areas—(1) Regulated articles of nursery stock and...

Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses.

PubMed

Liu, Yingqi; Zhu, Zixiang; Zhang, Miaotao; Zheng, Haixue

2015-10-28

Foot-and-mouth disease virus (FMDV) leader protein (L(pro)) is a papain-like proteinase, which plays an important role in FMDV pathogenesis. L(pro) exists as two forms, Lab and Lb, due to translation being initiated from two different start codons separated by 84 nucleotides. L(pro) self-cleaves from the nascent viral polyprotein precursor as the first mature viral protein. In addition to its role as a viral proteinase, L(pro) also has the ability to antagonize host antiviral effects. To promote FMDV replication, L(pro) can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β production; and (3) L(pro) can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules. In the light of recent functional and biochemical findings regarding L(pro), this review introduces the basic properties of L(pro) and the mechanisms by which it antagonizes host antiviral responses.

Overlapping and Distinct Molecular Determinants Dictating the Antiviral Activities of TRIM56 against Flaviviruses and Coronavirus

PubMed Central

Liu, Baoming; Li, Nan L.; Wang, Jie; Shi, Pei-Yong; Wang, Tianyi; Miller, Mark A.

2014-01-01

ABSTRACT The tripartite motif-containing (TRIM) proteins have emerged as a new class of host antiviral restriction factors, with several demonstrating roles in regulating innate antiviral responses. Of >70 known TRIMs, TRIM56 inhibits replication of bovine viral diarrhea virus, a ruminant pestivirus of the family Flaviviridae, but has no appreciable effect on vesicular stomatitis virus (VSV), a rhabdovirus. Yet the antiviral spectrum of TRIM56 remains undefined. In particular, how TRIM56 impacts human-pathogenic viruses is unknown. Also unclear are the molecular determinants governing the antiviral activities of TRIM56. Herein, we show that TRIM56 poses a barrier to infections by yellow fever virus (YFV), dengue virus serotype 2 (DENV2), and human coronavirus virus (HCoV) OC43 but not encephalomyocarditis virus (EMCV). Moreover, by engineering cell lines conditionally expressing various TRIM56 mutants, we demonstrated that TRIM56's antiflavivirus effects required both the E3 ligase activity that lies in the N-terminal RING domain and the integrity of its C-terminal portion, while the restriction of HCoV-OC43 relied upon the TRIM56 E3 ligase activity alone. Furthermore, TRIM56 was revealed to impair YFV and DENV2 propagation by suppressing intracellular viral RNA accumulation but to compromise HCoV-OC43 infection at a later step in the viral life cycle, suggesting that distinct TRIM56 domains accommodate differing antiviral mechanisms. Altogether, TRIM56 is a versatile antiviral host factor that confers resistance to YFV, DENV2, and HCoV-OC43 through overlapping and distinct molecular determinants. IMPORTANCE We previously reported tripartite motif protein 56 (TRIM56) as a host restriction factor of bovine viral diarrhea virus, a ruminant pathogen. However, the impact of TRIM56 on human-pathogenic RNA viruses is unknown. Herein, we demonstrate that TRIM56 restricts two medically important flaviviruses, yellow fever virus (YFV) and dengue virus serotype 2 (DENV2), and a human coronavirus, HCoV-OC43, but not encephalomyocarditis virus, a picornavirus. Further, we show that TRIM56-mediated inhibition of HCoV-OC43 multiplication depends solely on its E3 ligase activity, whereas its restriction of YFV and DENV2 requires both the E3 ligase activity and integrity of the C-terminal portion. The differing molecular determinants appear to accommodate distinct antiviral mechanisms TRIM56 adopts to target different families of viruses; while TRIM56 curbs intracellular YFV/DENV2 RNA replication, it acts at a later step in HCoV-OC43 life cycle. These novel findings illuminate the molecular basis of the versatility and specificity of TRIM56's antiviral activities against positive-strand RNA viruses. PMID:25253338

Overlapping and distinct molecular determinants dictating the antiviral activities of TRIM56 against flaviviruses and coronavirus.

PubMed

Liu, Baoming; Li, Nan L; Wang, Jie; Shi, Pei-Yong; Wang, Tianyi; Miller, Mark A; Li, Kui

2014-12-01

The tripartite motif-containing (TRIM) proteins have emerged as a new class of host antiviral restriction factors, with several demonstrating roles in regulating innate antiviral responses. Of >70 known TRIMs, TRIM56 inhibits replication of bovine viral diarrhea virus, a ruminant pestivirus of the family Flaviviridae, but has no appreciable effect on vesicular stomatitis virus (VSV), a rhabdovirus. Yet the antiviral spectrum of TRIM56 remains undefined. In particular, how TRIM56 impacts human-pathogenic viruses is unknown. Also unclear are the molecular determinants governing the antiviral activities of TRIM56. Herein, we show that TRIM56 poses a barrier to infections by yellow fever virus (YFV), dengue virus serotype 2 (DENV2), and human coronavirus virus (HCoV) OC43 but not encephalomyocarditis virus (EMCV). Moreover, by engineering cell lines conditionally expressing various TRIM56 mutants, we demonstrated that TRIM56's antiflavivirus effects required both the E3 ligase activity that lies in the N-terminal RING domain and the integrity of its C-terminal portion, while the restriction of HCoV-OC43 relied upon the TRIM56 E3 ligase activity alone. Furthermore, TRIM56 was revealed to impair YFV and DENV2 propagation by suppressing intracellular viral RNA accumulation but to compromise HCoV-OC43 infection at a later step in the viral life cycle, suggesting that distinct TRIM56 domains accommodate differing antiviral mechanisms. Altogether, TRIM56 is a versatile antiviral host factor that confers resistance to YFV, DENV2, and HCoV-OC43 through overlapping and distinct molecular determinants. We previously reported tripartite motif protein 56 (TRIM56) as a host restriction factor of bovine viral diarrhea virus, a ruminant pathogen. However, the impact of TRIM56 on human-pathogenic RNA viruses is unknown. Herein, we demonstrate that TRIM56 restricts two medically important flaviviruses, yellow fever virus (YFV) and dengue virus serotype 2 (DENV2), and a human coronavirus, HCoV-OC43, but not encephalomyocarditis virus, a picornavirus. Further, we show that TRIM56-mediated inhibition of HCoV-OC43 multiplication depends solely on its E3 ligase activity, whereas its restriction of YFV and DENV2 requires both the E3 ligase activity and integrity of the C-terminal portion. The differing molecular determinants appear to accommodate distinct antiviral mechanisms TRIM56 adopts to target different families of viruses; while TRIM56 curbs intracellular YFV/DENV2 RNA replication, it acts at a later step in HCoV-OC43 life cycle. These novel findings illuminate the molecular basis of the versatility and specificity of TRIM56's antiviral activities against positive-strand RNA viruses. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Visualization of a proteasome-independent intermediate during restriction of HIV-1 by rhesus TRIM5α

PubMed Central

Campbell, Edward M.; Perez, Omar; Anderson, Jenny L.; Hope, Thomas J.

2008-01-01

TRIM5 proteins constitute a class of restriction factors that prevent host cell infection by retroviruses from different species. TRIM5α restricts retroviral infection early after viral entry, before the generation of viral reverse transcription products. However, the underlying restriction mechanism remains unclear. In this study, we show that during rhesus macaque TRIM5α (rhTRIM5α)–mediated restriction of HIV-1 infection, cytoplasmic HIV-1 viral complexes can associate with concentrations of TRIM5α protein termed cytoplasmic bodies. We observe a dynamic interaction between rhTRIM5α and cytoplasmic HIV-1 viral complexes, including the de novo formation of rhTRIM5α cytoplasmic body–like structures around viral complexes. We observe that proteasome inhibition allows HIV-1 to remain stably sequestered into large rhTRIM5α cytoplasmic bodies, preventing the clearance of HIV-1 viral complexes from the cytoplasm and revealing an intermediate in the restriction process. Furthermore, we can measure no loss of capsid protein from viral complexes arrested at this intermediate step in restriction, suggesting that any rhTRIM5α-mediated loss of capsid protein requires proteasome activity. PMID:18250195

Duck Interferon-Inducible Transmembrane Protein 3 Mediates Restriction of Influenza Viruses.

PubMed

Blyth, Graham A D; Chan, Wing Fuk; Webster, Robert G; Magor, Katharine E

2016-01-01

Interferon-inducible transmembrane proteins (IFITMs) can restrict the entry of a wide range of viruses. IFITM3 localizes to endosomes and can potently restrict the replication of influenza A viruses (IAV) and several other viruses that also enter host cells through the endocytic pathway. Here, we investigate whether IFITMs are involved in protection in ducks, the natural host of influenza virus. We identify and sequence duck IFITM1, IFITM2, IFITM3, and IFITM5. Using quantitative PCR (qPCR), we demonstrate the upregulation of these genes in lung tissue in response to highly pathogenic IAV infection by 400-fold, 30-fold, 30-fold, and 5-fold, respectively. We express each IFITM in chicken DF-1 cells and show duck IFITM1 localizes to the cell surface, while IFITM3 localizes to LAMP1-containing compartments. DF-1 cells stably expressing duck IFITM3 (but not IFITM1 or IFITM2) show increased restriction of replication of H1N1, H6N2, and H11N9 IAV strains but not vesicular stomatitis virus. Although duck and human IFITM3 share only 38% identity, critical residues for viral restriction are conserved. We generate chimeric and mutant IFITM3 proteins and show duck IFITM3 does not require its N-terminal domain for endosomal localization or antiviral function; however, this N-terminal end confers endosomal localization and antiviral function on IFITM1. In contrast to mammalian IFITM3, the conserved YXXθ endocytosis signal sequence in the N-terminal domain of duck IFITM3 is not essential for correct endosomal localization. Despite significant structural and amino acid divergence, presumably due to host-virus coevolution, duck IFITM3 is functional against IAV. Immune IFITM genes are poorly conserved across species, suggesting that selective pressure from host-specific viruses has driven this divergence. We wondered whether coevolution between viruses and their natural host would result in the evasion of IFITM restriction. Ducks are the natural host of avian influenza A viruses and display few or no disease symptoms upon infection with most strains, including highly pathogenic avian influenza. We have characterized the duck IFITM locus and identified IFITM3 as an important restrictor of several influenza A viruses, including avian strains. With only 38% amino acid identity to human IFITM3, duck IFITM3 possesses antiviral function against influenza virus. Thus, despite long coevolution of virus and host effectors in the natural host, influenza virus evasion of IFITM3 restriction in ducks is not apparent. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The Trw Type IV Secretion System of Bartonella Mediates Host-Specific Adhesion to Erythrocytes

PubMed Central

Vayssier-Taussat, Muriel; Le Rhun, Danielle; Deng, Hong Kuan; Biville, Francis; Cescau, Sandra; Danchin, Antoine; Marignac, Geneviève; Lenaour, Evelyne; Boulouis, Henri Jean; Mavris, Maria; Arnaud, Lionel; Yang, Huanming; Wang, Jing; Quebatte, Maxime; Engel, Philipp; Saenz, Henri; Dehio, Christoph

2010-01-01

Bacterial pathogens typically infect only a limited range of hosts; however, the genetic mechanisms governing host-specificity are poorly understood. The α-proteobacterial genus Bartonella comprises 21 species that cause host-specific intraerythrocytic bacteremia as hallmark of infection in their respective mammalian reservoirs, including the human-specific pathogens Bartonella quintana and Bartonella bacilliformis that cause trench fever and Oroya fever, respectively. Here, we have identified bacterial factors that mediate host-specific erythrocyte colonization in the mammalian reservoirs. Using mouse-specific Bartonella birtlesii, human-specific Bartonella quintana, cat-specific Bartonella henselae and rat-specific Bartonella tribocorum, we established in vitro adhesion and invasion assays with isolated erythrocytes that fully reproduce the host-specificity of erythrocyte infection as observed in vivo. By signature-tagged mutagenesis of B. birtlesii and mutant selection in a mouse infection model we identified mutants impaired in establishing intraerythrocytic bacteremia. Among 45 abacteremic mutants, five failed to adhere to and invade mouse erythrocytes in vitro. The corresponding genes encode components of the type IV secretion system (T4SS) Trw, demonstrating that this virulence factor laterally acquired by the Bartonella lineage is directly involved in adherence to erythrocytes. Strikingly, ectopic expression of Trw of rat-specific B. tribocorum in cat-specific B. henselae or human-specific B. quintana expanded their host range for erythrocyte infection to rat, demonstrating that Trw mediates host-specific erythrocyte infection. A molecular evolutionary analysis of the trw locus further indicated that the variable, surface-located TrwL and TrwJ might represent the T4SS components that determine host-specificity of erythrocyte parasitism. In conclusion, we show that the laterally acquired Trw T4SS diversified in the Bartonella lineage to facilitate host-restricted adhesion to erythrocytes in a wide range of mammals. PMID:20548954

Lentiviral gene therapy against human immunodeficiency virus type 1, using a novel human TRIM21-cyclophilin A restriction factor.

PubMed

Chan, Emma; Schaller, Torsten; Eddaoudi, Ayad; Zhan, Hong; Tan, Choon Ping; Jacobsen, Marianne; Thrasher, Adrian J; Towers, Greg J; Qasim, Waseem

2012-11-01

TRIM5α (tripartite motif-containing protein-5, isoform α)-cyclophilin A fusion proteins are anti-human immunodeficiency virus (HIV) restriction factors that have evolved in certain nonhuman primates over millions of years and protect against HIV and related viruses. Restriction by TRIM5αCypA is potent and highly resistant to viral escape by mutation and, in combination with a suitable gene delivery platform, offers the possibility of novel therapeutic approaches against HIV. Here we report that lentiviral vector delivery of human mimics of TRIM5α-cyclophilin A (TRIM5CypA) fusion proteins afforded robust and durable protection against HIV-1, but resulted in downregulation of host cell antiviral responses mediated by endogenous TRIM5α. We found that substitution of TRIM5α RING, B-box, and coiled-coil domains with similar domains from a related TRIM protein, TRIM21, produced a novel and equally potent inhibitor of HIV-1. Both TRIM5CypA and TRIM21CypA inhibited transduction by HIV-1-derived viral vectors and prevented propagation of replication-competent HIV-1 in human cell lines and in primary human T cells. Restriction factor-modified T cells exhibited preferential survival in the presence of wild-type HIV. Restriction was dependent on proteasomal degradation and was reversed in the presence of the cyclophilin inhibitor cyclosporin. Importantly, TRIM21CypA did not disturb endogenous TRIM5α-mediated restriction of gammaretroviral infection. Furthermore, endogenous TRIM21 antiviral activity was assessed by measuring inhibition of adenovirus-antibody complexes and was found to be preserved in all TRIMCypA-modified groups. We conclude that lentivirus-mediated expression of the novel chimeric restriction factor TRIM21CypA provides highly potent protection against HIV-1 without loss of normal innate immune TRIM activity.

Host-imposed manganese starvation of invading pathogens: two routes to the same destination

PubMed Central

Morey, Jacqueline R.; McDevitt, Christopher A.; Kehl-Fie, Thomas E.

2015-01-01

During infection invading pathogens must acquire all essential nutrients, including first row transition metals, from the host. To combat invaders, the host exploits this fact and restricts the availability of these nutrients using a defense mechanism known as nutritional immunity. While iron sequestration is the most well-known aspect of this defense, recent work has revealed that the host restricts the availability of other essential elements, notably manganese, during infection. Furthermore, these studies have revealed that the host utilizes multiple strategies that extend beyond metal sequestration to prevent bacteria from obtaining these metals. This review will discuss the mechanisms by which bacteria attempt to obtain the essential first row transition metal ion manganese during infection, and the approaches utilized by the host to prevent this occurrence. In addition, this review will discuss the impact of host-imposed manganese starvation on invading bacteria. PMID:25836716

Primary Role for Toll-Like Receptor-Driven Tumor Necrosis Factor Rather than Cytosolic Immune Detection in Restricting Coxiella burnetii Phase II Replication within Mouse Macrophages

PubMed Central

Bradley, William P.; Boyer, Mark A.; Nguyen, Hieu T.; Birdwell, L. Dillon; Yu, Janet; Ribeiro, Juliana M.; Roy, Craig R.

2016-01-01

Coxiella burnetii replicates within permissive host cells by employing a Dot/Icm type IV secretion system (T4SS) to translocate effector proteins that direct the formation of a parasitophorous vacuole. C57BL/6 mouse macrophages restrict the intracellular replication of the C. burnetii Nine Mile phase II (NMII) strain. However, eliminating Toll-like receptor 2 (TLR2) permits bacterial replication, indicating that the restriction of bacterial replication is immune mediated. Here, we examined whether additional innate immune pathways are employed by C57BL/6 macrophages to sense and restrict NMII replication. In addition to the known role of TLR2 in detecting and restricting NMII infection, we found that TLR4 also contributes to cytokine responses but is not required to restrict bacterial replication. Furthermore, the TLR signaling adaptors MyD88 and Trif are required for cytokine responses and restricting bacterial replication. The C. burnetii NMII T4SS translocates bacterial products into C57BL/6 macrophages. However, there was little evidence of cytosolic immune sensing of NMII, as there was a lack of inflammasome activation, T4SS-dependent cytokine responses, and robust type I interferon (IFN) production, and these pathways were not required to restrict bacterial replication. Instead, endogenous tumor necrosis factor (TNF) produced upon TLR sensing of C. burnetii NMII was required to control bacterial replication. Therefore, our findings indicate a primary role for TNF produced upon immune detection of C. burnetii NMII by TLRs, rather than cytosolic PRRs, in enabling C57BL/6 macrophages to restrict bacterial replication. PMID:26787725

Three-Dimensional Structural Characterization of HIV-1 Tethered to Human Cells

PubMed Central

Strauss, Joshua D.; Hammonds, Jason E.; Yi, Hong; Ding, Lingmei

2015-01-01

ABSTRACT Tetherin (BST2, CD317, or HM1.24) is a host cellular restriction factor that prevents the release of enveloped viruses by mechanically linking virions to the plasma membrane. The precise arrangement of tetherin molecules at the plasma membrane site of HIV-1 assembly, budding, and restriction is not well understood. To gain insight into the biophysical mechanism underlying tetherin-mediated restriction of HIV-1, we utilized cryo-electron tomography (cryo-ET) to directly visualize HIV-1 virus-like particles (VLPs) and virions tethered to human cells in three dimensions (3D). Rod-like densities that we refer to as tethers were seen connecting HIV-1 virions to each other and to the plasma membrane. Native immunogold labeling showed tetherin molecules located on HIV-1 VLPs and virions in positions similar to those of the densities observed by cryo-ET. The location of the tethers with respect to the ordered immature Gag lattice or mature conical core was random. However, tethers were not uniformly distributed on the viral membrane but rather formed clusters at sites of contact with the cell or other virions. Chains of tethered HIV-1 virions often were arranged in a linear fashion, primarily as single chains and, to a lesser degree, as branched chains. Distance measurements support the extended tetherin model, in which the coiled-coil ectodomains are oriented perpendicular with respect to the viral and plasma membranes. IMPORTANCE Tetherin is a cellular factor that restricts HIV-1 release by directly cross-linking the virus to the host cell plasma membrane. We used cryo-electron tomography to visualize HIV-1 tethered to human cells in 3D. We determined that tetherin-restricted HIV-1 virions were physically connected to each other or to the plasma membrane by filamentous tethers that resembled rods ∼15 nm in length, which is consistent with the extended tetherin model. In addition, we found the position of the tethers to be arbitrary relative to the ordered immature Gag lattice or the mature conical cores. However, when present as multiple copies, the tethers clustered at the interface between virions. Tethered HIV-1 virions were arranged in a linear fashion, with the majority as single chains. This study advances our understanding of tetherin-mediated HIV-1 restriction by defining the spatial arrangement and orientation of tetherin molecules at sites of HIV-1 restriction. PMID:26582000

Interferon-inducible effector mechanisms in cell-autonomous immunity

PubMed Central

MacMicking, John D.

2014-01-01

Interferons (IFNs) induce the expression of hundreds of genes as part of an elaborate antimicrobial programme designed to combat infection in all nucleated cells — a process termed cell-autonomous immunity. As described in this Review, recent genomic and subgenomic analyses have begun to assign functional properties to novel IFN-inducible effector proteins that restrict bacteria, protozoa and viruses in different subcellular compartments and at different stages of the pathogen life cycle. Several newly described host defence factors also participate in canonical oxidative and autophagic pathways by spatially coordinating their activities to enhance microbial killing. Together, these IFN-induced effector networks help to confer vertebrate host resistance to a vast and complex microbial world. PMID:22531325

Infected cell protein 0 functional domains and their coordination in herpes simplex virus replication

PubMed Central

Gu, Haidong

2016-01-01

Herpes simplex virus 1 (HSV-1) is a ubiquitous human pathogen that establishes latent infection in ganglia neurons. Its unique life cycle requires a balanced “conquer and compromise” strategy to deal with the host anti-viral defenses. One of HSV-1 α (immediate early) gene products, infected cell protein 0 (ICP0), is a multifunctional protein that interacts with and modulates a wide range of cellular defensive pathways. These pathways may locate in different cell compartments, which then migrate or exchange factors upon stimulation, for the purpose of a concerted and effective defense. ICP0 is able to simultaneously attack multiple host pathways by either degrading key restrictive factors or modifying repressive complexes. This is a viral protein that contains an E3 ubiquitin ligase, translocates among different cell compartments and interacts with major defensive complexes. The multiple functional domains of ICP0 can work independently and at the same time coordinate with each other. Dissecting the functional domains of ICP0 and delineating the coordination of these domains will help us understand HSV-1 pathogenicity as well as host defense mechanisms. This article focuses on describing individual ICP0 domains, their biochemical properties and their implication in HSV-1 infection. By putting individual domain functions back into the picture of host anti-viral defense network, this review seeks to elaborate the complex interactions between HSV-1 and its host. PMID:26870669

Novel Role for Protein Inhibitor of Activated STAT 4 (PIAS4) in the Restriction of Herpes Simplex Virus 1 by the Cellular Intrinsic Antiviral Immune Response.

PubMed

Conn, Kristen L; Wasson, Peter; McFarlane, Steven; Tong, Lily; Brown, James R; Grant, Kyle G; Domingues, Patricia; Boutell, Chris

2016-05-01

Small ubiquitin-like modifier (SUMO) is used by the intrinsic antiviral immune response to restrict viral pathogens, such as herpes simplex virus 1 (HSV-1). Despite characterization of the host factors that rely on SUMOylation to exert their antiviral effects, the enzymes that mediate these SUMOylation events remain to be defined. We show that unconjugated SUMO levels are largely maintained throughout infection regardless of the presence of ICP0, the HSV-1 SUMO-targeted ubiquitin ligase. Moreover, in the absence of ICP0, high-molecular-weight SUMO-conjugated proteins do not accumulate if HSV-1 DNA does not replicate. These data highlight the continued importance for SUMO signaling throughout infection. We show that the SUMO ligase protein inhibitor of activated STAT 4 (PIAS4) is upregulated during HSV-1 infection and localizes to nuclear domains that contain viral DNA. PIAS4 is recruited to sites associated with HSV-1 genome entry through SUMO interaction motif (SIM)-dependent mechanisms that are destabilized by ICP0. In contrast, PIAS4 accumulates in replication compartments through SIM-independent mechanisms irrespective of ICP0 expression. Depletion of PIAS4 enhances the replication of ICP0-null mutant HSV-1, which is susceptible to restriction by the intrinsic antiviral immune response. The mechanisms of PIAS4-mediated restriction are synergistic with the restriction mechanisms of a characterized intrinsic antiviral factor, promyelocytic leukemia protein, and are antagonized by ICP0. We provide the first evidence that PIAS4 is an intrinsic antiviral factor. This novel role for PIAS4 in intrinsic antiviral immunity contrasts with the known roles of PIAS proteins as suppressors of innate immunity. Posttranslational modifications with small ubiquitin-like modifier (SUMO) proteins regulate multiple aspects of host immunity and viral replication. The protein inhibitor of activated STAT (PIAS) family of SUMO ligases is predominantly associated with the suppression of innate immune signaling. We now identify a unique and contrasting role for PIAS proteins as positive regulators of the intrinsic antiviral immune response to herpes simplex virus 1 (HSV-1) infection. We show that PIAS4 relocalizes to nuclear domains that contain viral DNA throughout infection. Depletion of PIAS4, either alone or in combination with the intrinsic antiviral factor promyelocytic leukemia protein, significantly impairs the intrinsic antiviral immune response to HSV-1 infection. Our data reveal a novel and dynamic role for PIAS4 in the cellular-mediated restriction of herpesviruses and establish a new functional role for the PIAS family of SUMO ligases in the intrinsic antiviral immune response to DNA virus infection. Copyright © 2016 Conn et al.

Novel Role for Protein Inhibitor of Activated STAT 4 (PIAS4) in the Restriction of Herpes Simplex Virus 1 by the Cellular Intrinsic Antiviral Immune Response

PubMed Central

Conn, Kristen L.; Wasson, Peter; McFarlane, Steven; Tong, Lily; Brown, James R.; Grant, Kyle G.; Domingues, Patricia

2016-01-01

ABSTRACT Small ubiquitin-like modifier (SUMO) is used by the intrinsic antiviral immune response to restrict viral pathogens, such as herpes simplex virus 1 (HSV-1). Despite characterization of the host factors that rely on SUMOylation to exert their antiviral effects, the enzymes that mediate these SUMOylation events remain to be defined. We show that unconjugated SUMO levels are largely maintained throughout infection regardless of the presence of ICP0, the HSV-1 SUMO-targeted ubiquitin ligase. Moreover, in the absence of ICP0, high-molecular-weight SUMO-conjugated proteins do not accumulate if HSV-1 DNA does not replicate. These data highlight the continued importance for SUMO signaling throughout infection. We show that the SUMO ligase protein inhibitor of activated STAT 4 (PIAS4) is upregulated during HSV-1 infection and localizes to nuclear domains that contain viral DNA. PIAS4 is recruited to sites associated with HSV-1 genome entry through SUMO interaction motif (SIM)-dependent mechanisms that are destabilized by ICP0. In contrast, PIAS4 accumulates in replication compartments through SIM-independent mechanisms irrespective of ICP0 expression. Depletion of PIAS4 enhances the replication of ICP0-null mutant HSV-1, which is susceptible to restriction by the intrinsic antiviral immune response. The mechanisms of PIAS4-mediated restriction are synergistic with the restriction mechanisms of a characterized intrinsic antiviral factor, promyelocytic leukemia protein, and are antagonized by ICP0. We provide the first evidence that PIAS4 is an intrinsic antiviral factor. This novel role for PIAS4 in intrinsic antiviral immunity contrasts with the known roles of PIAS proteins as suppressors of innate immunity. IMPORTANCE Posttranslational modifications with small ubiquitin-like modifier (SUMO) proteins regulate multiple aspects of host immunity and viral replication. The protein inhibitor of activated STAT (PIAS) family of SUMO ligases is predominantly associated with the suppression of innate immune signaling. We now identify a unique and contrasting role for PIAS proteins as positive regulators of the intrinsic antiviral immune response to herpes simplex virus 1 (HSV-1) infection. We show that PIAS4 relocalizes to nuclear domains that contain viral DNA throughout infection. Depletion of PIAS4, either alone or in combination with the intrinsic antiviral factor promyelocytic leukemia protein, significantly impairs the intrinsic antiviral immune response to HSV-1 infection. Our data reveal a novel and dynamic role for PIAS4 in the cellular-mediated restriction of herpesviruses and establish a new functional role for the PIAS family of SUMO ligases in the intrinsic antiviral immune response to DNA virus infection. PMID:26937035

Homologous Recombination between Genetically Divergent Campylobacter fetus Lineages Supports Host-Associated Speciation

PubMed Central

Duim, Birgitta; van der Graaf-van Bloois, Linda; Wagenaar, Jaap A; Zomer, Aldert L

2018-01-01

Abstract Homologous recombination is a major driver of bacterial speciation. Genetic divergence and host association are important factors influencing homologous recombination. Here, we study these factors for Campylobacter fetus, which shows a distinct intraspecific host dichotomy. Campylobacter fetus subspecies fetus (Cff) and venerealis are associated with mammals, whereas C. fetus subsp. testudinum (Cft) is associated with reptiles. Recombination between these genetically divergent C. fetus lineages is extremely rare. Previously it was impossible to show whether this barrier to recombination was determined by the differential host preferences, by the genetic divergence between both lineages or by other factors influencing recombination, such as restriction-modification, CRISPR/Cas, and transformation systems. Fortuitously, a distinct C. fetus lineage (ST69) was found, which was highly related to mammal-associated C. fetus, yet isolated from a chelonian. The whole genome sequences of two C. fetus ST69 isolates were compared with those of mammal- and reptile-associated C. fetus strains for phylogenetic and recombination analysis. In total, 5.1–5.5% of the core genome of both ST69 isolates showed signs of recombination. Of the predicted recombination regions, 80.4% were most closely related to Cft, 14.3% to Cff, and 5.6% to C. iguaniorum. Recombination from C. fetus ST69 to Cft was also detected, but to a lesser extent and only in chelonian-associated Cft strains. This study shows that despite substantial genetic divergence no absolute barrier to homologous recombination exists between two distinct C. fetus lineages when occurring in the same host type, which provides valuable insights in bacterial speciation and evolution. PMID:29608720

Feline Immunodeficiency Virus Evolutionarily Acquires Two Proteins, Vif and Protease, Capable of Antagonizing Feline APOBEC3.

PubMed

Yoshikawa, Rokusuke; Takeuchi, Junko S; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Kimura, Yuichi; Ren, Fengrong; Miyazawa, Takayuki; Koyanagi, Yoshio; Sato, Kei

2017-06-01

The interplay between viral and host proteins has been well studied to elucidate virus-host interactions and their relevance to virulence. Mammalian genes encode apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins, which act as intrinsic restriction factors against lentiviruses. To overcome APOBEC3-mediated antiviral actions, lentiviruses have evolutionarily acquired an accessory protein, viral infectivity factor (Vif), and Vif degrades host APOBEC3 proteins via a ubiquitin/proteasome-dependent pathway. Although the Vif-APOBEC3 interaction and its evolutionary significance, particularly those of primate lentiviruses (including HIV) and primates (including humans), have been well investigated, those of nonprimate lentiviruses and nonprimates are poorly understood. Moreover, the factors that determine lentiviral pathogenicity remain unclear. Here, we focus on feline immunodeficiency virus (FIV), a pathogenic lentivirus in domestic cats, and the interaction between FIV Vif and feline APOBEC3 in terms of viral virulence and evolution. We reveal the significantly reduced diversity of FIV subtype B compared to that of other subtypes, which may associate with the low pathogenicity of this subtype. We also demonstrate that FIV subtype B Vif is less active with regard to feline APOBEC3 degradation. More intriguingly, we further reveal that FIV protease cleaves feline APOBEC3 in released virions. Taken together, our findings provide evidence that a lentivirus encodes two types of anti-APOBEC3 factors, Vif and viral protease. IMPORTANCE During the history of mammalian evolution, mammals coevolved with retroviruses, including lentiviruses. All pathogenic lentiviruses, excluding equine infectious anemia virus, have acquired the vif gene via evolution to combat APOBEC3 proteins, which are intrinsic restriction factors against exogenous lentiviruses. Here we demonstrate that FIV, a pathogenic lentivirus in domestic cats, antagonizes feline APOBEC3 proteins by both Vif and a viral protease. Furthermore, the Vif proteins of an FIV subtype (subtype B) have attenuated their anti-APOBEC3 activity through evolution. Our findings can be a clue to elucidate the complicated evolutionary processes by which lentiviruses adapt to mammals. Copyright © 2017 Yoshikawa et al.

Feline Immunodeficiency Virus Evolutionarily Acquires Two Proteins, Vif and Protease, Capable of Antagonizing Feline APOBEC3

PubMed Central

Yoshikawa, Rokusuke; Takeuchi, Junko S.; Yamada, Eri; Nakano, Yusuke; Misawa, Naoko; Kimura, Yuichi; Ren, Fengrong; Miyazawa, Takayuki; Koyanagi, Yoshio

2017-01-01

ABSTRACT The interplay between viral and host proteins has been well studied to elucidate virus-host interactions and their relevance to virulence. Mammalian genes encode apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins, which act as intrinsic restriction factors against lentiviruses. To overcome APOBEC3-mediated antiviral actions, lentiviruses have evolutionarily acquired an accessory protein, viral infectivity factor (Vif), and Vif degrades host APOBEC3 proteins via a ubiquitin/proteasome-dependent pathway. Although the Vif-APOBEC3 interaction and its evolutionary significance, particularly those of primate lentiviruses (including HIV) and primates (including humans), have been well investigated, those of nonprimate lentiviruses and nonprimates are poorly understood. Moreover, the factors that determine lentiviral pathogenicity remain unclear. Here, we focus on feline immunodeficiency virus (FIV), a pathogenic lentivirus in domestic cats, and the interaction between FIV Vif and feline APOBEC3 in terms of viral virulence and evolution. We reveal the significantly reduced diversity of FIV subtype B compared to that of other subtypes, which may associate with the low pathogenicity of this subtype. We also demonstrate that FIV subtype B Vif is less active with regard to feline APOBEC3 degradation. More intriguingly, we further reveal that FIV protease cleaves feline APOBEC3 in released virions. Taken together, our findings provide evidence that a lentivirus encodes two types of anti-APOBEC3 factors, Vif and viral protease. IMPORTANCE During the history of mammalian evolution, mammals coevolved with retroviruses, including lentiviruses. All pathogenic lentiviruses, excluding equine infectious anemia virus, have acquired the vif gene via evolution to combat APOBEC3 proteins, which are intrinsic restriction factors against exogenous lentiviruses. Here we demonstrate that FIV, a pathogenic lentivirus in domestic cats, antagonizes feline APOBEC3 proteins by both Vif and a viral protease. Furthermore, the Vif proteins of an FIV subtype (subtype B) have attenuated their anti-APOBEC3 activity through evolution. Our findings can be a clue to elucidate the complicated evolutionary processes by which lentiviruses adapt to mammals. PMID:28331087

Human Intestinal Enteroids: a New Model To Study Human Rotavirus Infection, Host Restriction, and Pathophysiology

PubMed Central

Saxena, Kapil; Blutt, Sarah E.; Ettayebi, Khalil; Zeng, Xi-Lei; Broughman, James R.; Crawford, Sue E.; Karandikar, Umesh C.; Sastri, Narayan P.; Conner, Margaret E.; Opekun, Antone R.; Graham, David Y.; Qureshi, Waqar; Sherman, Vadim; Foulke-Abel, Jennifer; In, Julie; Kovbasnjuk, Olga; Zachos, Nicholas C.; Donowitz, Mark

2015-01-01

ABSTRACT Human gastrointestinal tract research is limited by the paucity of in vitro intestinal cell models that recapitulate the cellular diversity and complex functions of human physiology and disease pathology. Human intestinal enteroid (HIE) cultures contain multiple intestinal epithelial cell types that comprise the intestinal epithelium (enterocytes and goblet, enteroendocrine, and Paneth cells) and are physiologically active based on responses to agonists. We evaluated these nontransformed, three-dimensional HIE cultures as models for pathogenic infections in the small intestine by examining whether HIEs from different regions of the small intestine from different patients are susceptible to human rotavirus (HRV) infection. Little is known about HRVs, as they generally replicate poorly in transformed cell lines, and host range restriction prevents their replication in many animal models, whereas many animal rotaviruses (ARVs) exhibit a broader host range and replicate in mice. Using HRVs, including the Rotarix RV1 vaccine strain, and ARVs, we evaluated host susceptibility, virus production, and cellular responses of HIEs. HRVs infect at higher rates and grow to higher titers than do ARVs. HRVs infect differentiated enterocytes and enteroendocrine cells, and viroplasms and lipid droplets are induced. Heterogeneity in replication was seen in HIEs from different patients. HRV infection and RV enterotoxin treatment of HIEs caused physiological lumenal expansion detected by time-lapse microscopy, recapitulating one of the hallmarks of rotavirus-induced diarrhea. These results demonstrate that HIEs are a novel pathophysiological model that will allow the study of HRV biology, including host restriction, cell type restriction, and virus-induced fluid secretion. IMPORTANCE Our research establishes HIEs as nontransformed cell culture models to understand human intestinal physiology and pathophysiology and the epithelial response, including host restriction of gastrointestinal infections such as HRV infection. HRVs remain a major worldwide cause of diarrhea-associated morbidity and mortality in children ≤5 years of age. Current in vitro models of rotavirus infection rely primarily on the use of animal rotaviruses because HRV growth is limited in most transformed cell lines and animal models. We demonstrate that HIEs are novel, cellularly diverse, and physiologically relevant epithelial cell cultures that recapitulate in vivo properties of HRV infection. HIEs will allow the study of HRV biology, including human host-pathogen and live, attenuated vaccine interactions; host and cell type restriction; virus-induced fluid secretion; cell-cell communication within the epithelium; and the epithelial response to infection in cultures from genetically diverse individuals. Finally, drug therapies to prevent/treat diarrheal disease can be tested in these physiologically active cultures. PMID:26446608

Improved electro-transformation of highly DNA-restrictive corynebacteria with DNA extracted from starved Escherichia coli.

PubMed

Ankri, S; Reyes, O; Leblon, G

1996-07-01

Differences of up to 33 000-fold in electro-transformability of highly DNA restrictive corynebacteria are observed in the DNA of a shuttle plasmid extracted from Escherichia coli hosts propagated in different nutritional conditions. Growth of the host in minimal medium increases plasmid transformability, whereas growth on rich media decreases it. In the E. coli DH5 alpha host, the starvation-dependent increase DNA transformability is reverted by supplementing with methionine, an obligate 5-adenosyl-methionine (SAM) precursor. This suggests that an E. coli nutritionally modulated SAM-dependent DNA-methyltransferase may be involved in this phenomenon.

Family-based linkage and association mapping reveals novel genes affecting Plum pox virus infection in Arabidopsis thaliana.

PubMed

Pagny, Gaëlle; Paulstephenraj, Pauline S; Poque, Sylvain; Sicard, Ophélie; Cosson, Patrick; Eyquard, Jean-Philippe; Caballero, Mélodie; Chague, Aurélie; Gourdon, Germain; Negrel, Lise; Candresse, Thierry; Mariette, Stéphanie; Decroocq, Véronique

2012-11-01

Sharka is a devastating viral disease caused by the Plum pox virus (PPV) in stone fruit trees and few sources of resistance are known in its natural hosts. Since any knowledge gained from Arabidopsis on plant virus susceptibility factors is likely to be transferable to crop species, Arabidopsis's natural variation was searched for host factors essential for PPV infection. To locate regions of the genome associated with susceptibility to PPV, linkage analysis was performed on six biparental populations as well as on multiparental lines. To refine quantitative trait locus (QTL) mapping, a genome-wide association analysis was carried out using 147 Arabidopsis accessions. Evidence was found for linkage on chromosomes 1, 3 and 5 with restriction of PPV long-distance movement. The most relevant signals occurred within a region at the bottom of chromosome 3, which comprises seven RTM3-like TRAF domain-containing genes. Since the resistance mechanism analyzed here is recessive and the rtm3 knockout mutant is susceptible to PPV infection, it suggests that other gene(s) present in the small identified region encompassing RTM3 are necessary for PPV long-distance movement. In consequence, we report here the occurrence of host factor(s) that are indispensable for virus long-distance movement. © 2012 INRA. New Phytologist © 2012 New Phytologist Trust.

Modeling Powassan virus infection in Peromyscus leucopus, a natural host

PubMed Central

Meade-White, Kimberly; Saturday, Greg; Scott, Dana; Bloom, Marshall E.

2017-01-01

The tick-borne flavivirus, Powassan virus (POWV) causes life-threatening encephalitis in humans in North America and Europe. POWV is transmitted by ixodid tick vectors that feed on small to medium-sized mammals, such as Peromyscus leucopus mice, which may serve as either reservoir, bridge or amplification hosts. Intraperitoneal and intracranial inoculation of 4-week old Peromyscus leucopus mice with 103 PFU of POWV did not result in overt clinical signs of disease. However, following intracranial inoculation, infected mice seroconverted to POWV and histopathological examinations revealed that the mice uniformly developed mild lymphocytic perivascular cuffing and microgliosis in the brain and spinal cord from 5 to 15 days post infection (dpi), suggesting an early inflammatory response. In contrast, intracranial inoculation of 4-week old C57BL/6 and BALB/c mice was lethal by 5 dpi. Intraperitoneal inoculation was lethal in BALB/c mice, but 40% (2/5) of C57BL/6 mice survived. We concluded that Peromyscus leucopus mice infected i.c. with a lethal dose of POWV support a limited infection, restricted to the central nervous system and mount an antibody response to the virus. However, they fail to develop clinical signs of disease and are able to control the infection. These results suggest the involvement of restriction factors, and the mechanism by which Peromyscus leucopus mice restrict POWV infection remains under study. PMID:28141800

Modeling Powassan virus infection in Peromyscus leucopus, a natural host.

PubMed

Mlera, Luwanika; Meade-White, Kimberly; Saturday, Greg; Scott, Dana; Bloom, Marshall E

2017-01-01

The tick-borne flavivirus, Powassan virus (POWV) causes life-threatening encephalitis in humans in North America and Europe. POWV is transmitted by ixodid tick vectors that feed on small to medium-sized mammals, such as Peromyscus leucopus mice, which may serve as either reservoir, bridge or amplification hosts. Intraperitoneal and intracranial inoculation of 4-week old Peromyscus leucopus mice with 103 PFU of POWV did not result in overt clinical signs of disease. However, following intracranial inoculation, infected mice seroconverted to POWV and histopathological examinations revealed that the mice uniformly developed mild lymphocytic perivascular cuffing and microgliosis in the brain and spinal cord from 5 to 15 days post infection (dpi), suggesting an early inflammatory response. In contrast, intracranial inoculation of 4-week old C57BL/6 and BALB/c mice was lethal by 5 dpi. Intraperitoneal inoculation was lethal in BALB/c mice, but 40% (2/5) of C57BL/6 mice survived. We concluded that Peromyscus leucopus mice infected i.c. with a lethal dose of POWV support a limited infection, restricted to the central nervous system and mount an antibody response to the virus. However, they fail to develop clinical signs of disease and are able to control the infection. These results suggest the involvement of restriction factors, and the mechanism by which Peromyscus leucopus mice restrict POWV infection remains under study.

Cellular innate immunity and restriction of viral infection: implications for lentiviral gene therapy in human hematopoietic cells.

PubMed

Kajaste-Rudnitski, Anna; Naldini, Luigi

2015-04-01

Hematopoietic gene therapy has tremendous potential to treat human disease. Nevertheless, for gene therapy to be efficacious, effective gene transfer into target cells must be reached without inducing detrimental effects on their biological properties. This remains a great challenge for the field as high vector doses and prolonged ex vivo culture conditions are still required to reach significant transduction levels of clinically relevant human hematopoietic stem and progenitor cells (HSPCs), while other potential target cells such as primary macrophages can hardly be transduced. The reasons behind poor permissiveness of primary human hematopoietic cells to gene transfer partly reside in the retroviral origin of lentiviral vectors (LVs). In particular, host antiviral factors referred to as restriction factors targeting the retroviral life cycle can hamper LV transduction efficiency. Furthermore, LVs may activate innate immune sensors not only in differentiated hematopoietic cells but also in HSPCs, with potential consequences on transduction efficiency as well as their biological properties. Therefore, better understanding of the vector-host interactions in the context of hematopoietic gene transfer is important for the development of safer and more efficient gene therapy strategies. In this review, we briefly summarize the current knowledge regarding innate immune recognition of lentiviruses in primary human hematopoietic cells as well as discuss its relevance for LV-based ex vivo gene therapy approaches.

The interferon response circuit in antiviral host defense.

PubMed

Haller, O; Weber, F

2009-01-01

Viruses have learned to multiply in the face of a powerful innate and adaptive immune response of the host. They have evolved multiple strategies to evade the interferon (IFN) system which would otherwise limit virus growth at an early stage of infection. IFNs induce the synthesis of a range of antiviral proteins which serve as cell-autonomous intrinsic restriction factors. For example, the dynamin-like MxA GTPase inhibits the multiplication of influenza and bunyaviruses (such as La Crosse virus, Hantaan virus, Rift Valley Fever virus, and Crimean-Congo hemorrhagic fever virus) by binding and sequestering the nucleocapsid protein into large perinuclear complexes. To overcome such intracellular restrictions, virulent viruses either inhibit IFN synthesis, bind and inactivate secreted IFN molecules, block IFN-activated signaling, or disturb the action of IFN-induced antiviral proteins. Many viruses produce specialized proteins to disarm the danger signal or express virulence genes that target members of the IFN regulatory factor family (IRFs) or components of the JAK-STAT signaling pathway. An alternative evasion strategy is based on extreme viral replication speed which out-competes the IFN response. The identification of viral proteins with IFN antagonistic functions has great implications for disease prevention and therapy. Virus mutants lacking IFN antagonistic properties represent safe yet highly immunogenic candidate vaccines. Furthermore, novel drugs intercepting viral IFN-antagonists could be used to disarm the viral intruders.

Characterising the biology of novel lytic bacteriophages infecting multidrug resistant Klebsiella pneumoniae.

PubMed

Kęsik-Szeloch, Agata; Drulis-Kawa, Zuzanna; Weber-Dąbrowska, Beata; Kassner, Jerzy; Majkowska-Skrobek, Grażyna; Augustyniak, Daria; Lusiak-Szelachowska, Marzanna; Zaczek, Maciej; Górski, Andrzej; Kropinski, Andrew M

2013-03-28

Members of the genus Klebsiella are among the leading microbial pathogens associated with nosocomial infection. The increased incidence of antimicrobial resistance in these species has propelled the need for alternate/combination therapeutic regimens to aid clinical treatment. Bacteriophage therapy forms one of these alternate strategies. Electron microscopy, burst size, host range, sensitivity of phage particles to temperature, chloroform, pH, and restriction digestion of phage DNA were used to characterize Klebsiella phages. Of the 32 isolated phages eight belonged to the family Myoviridae, eight to the Siphoviridae whilst the remaining 16 belonged to the Podoviridae. The host range of these phages was characterised against 254 clinical Enterobacteriaceae strains including multidrug resistant Klebsiella isolates producing extended-spectrum beta-lactamases (ESBLs). Based on their lytic potential, six of the phages were further characterised for burst size, physicochemical properties and sensitivity to restriction endonuclease digestion. In addition, five were fully sequenced. Multiple phage-encoded host resistance mechanisms were identified. The Siphoviridae phage genomes (KP16 and KP36) contained low numbers of host restriction sites similar to the strategy found in T7-like phages (KP32). In addition, phage KP36 encoded its own DNA adenine methyltransferase. The φKMV-like KP34 phage was sensitive to all endonucleases used in this study. Dam methylation of KP34 DNA was detected although this was in the absence of an identifiable phage encoded methyltransferase. The Myoviridae phages KP15 and KP27 both carried Dam and Dcm methyltransferase genes and other anti-restriction mechanisms elucidated in previous studies. No other anti-restriction mechanisms were found, e.g. atypical nucleotides (hmC or glucosyl hmC), although Myoviridae phage KP27 encodes an unknown anti-restriction mechanism that needs further investigation.

A Kinome-Wide Small Interfering RNA Screen Identifies Proviral and Antiviral Host Factors in Severe Acute Respiratory Syndrome Coronavirus Replication, Including Double-Stranded RNA-Activated Protein Kinase and Early Secretory Pathway Proteins

PubMed Central

de Wilde, Adriaan H.; Wannee, Kazimier F.; Scholte, Florine E. M.; Goeman, Jelle J.; ten Dijke, Peter; Snijder, Eric J.

2015-01-01

ABSTRACT To identify host factors relevant for severe acute respiratory syndrome-coronavirus (SARS-CoV) replication, we performed a small interfering RNA (siRNA) library screen targeting the human kinome. Protein kinases are key regulators of many cellular functions, and the systematic knockdown of their expression should provide a broad perspective on factors and pathways promoting or antagonizing coronavirus replication. In addition to 40 proteins that promote SARS-CoV replication, our study identified 90 factors exhibiting an antiviral effect. Pathway analysis grouped subsets of these factors in specific cellular processes, including the innate immune response and the metabolism of complex lipids, which appear to play a role in SARS-CoV infection. Several factors were selected for in-depth validation in follow-up experiments. In cells depleted for the β2 subunit of the coatomer protein complex (COPB2), the strongest proviral hit, we observed reduced SARS-CoV protein expression and a >2-log reduction in virus yield. Knockdown of the COPB2-related proteins COPB1 and Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1) also suggested that COPI-coated vesicles and/or the early secretory pathway are important for SARS-CoV replication. Depletion of the antiviral double-stranded RNA-activated protein kinase (PKR) enhanced virus replication in the primary screen, and validation experiments confirmed increased SARS-CoV protein expression and virus production upon PKR depletion. In addition, cyclin-dependent kinase 6 (CDK6) was identified as a novel antiviral host factor in SARS-CoV replication. The inventory of pro- and antiviral host factors and pathways described here substantiates and expands our understanding of SARS-CoV replication and may contribute to the identification of novel targets for antiviral therapy. IMPORTANCE Replication of all viruses, including SARS-CoV, depends on and is influenced by cellular pathways. Although substantial progress has been made in dissecting the coronavirus replicative cycle, our understanding of the host factors that stimulate (proviral factors) or restrict (antiviral factors) infection remains far from complete. To study the role of host proteins in SARS-CoV infection, we set out to systematically identify kinase-regulated processes that influence virus replication. Protein kinases are key regulators in signal transduction, controlling a wide variety of cellular processes, and many of them are targets of approved drugs and other compounds. Our screen identified a variety of hits and will form the basis for more detailed follow-up studies that should contribute to a better understanding of SARS-CoV replication and coronavirus-host interactions in general. The identified factors could be interesting targets for the development of host-directed antiviral therapy to treat infections with SARS-CoV or other pathogenic coronaviruses. PMID:26041291

Strain diversity and host specificity in a specialized gut symbiont of honeybees and bumblebees.

PubMed

Powell, Elijah; Ratnayeke, Nalin; Moran, Nancy A

2016-09-01

Host-restricted lineages of gut bacteria often include many closely related strains, but this fine-scale diversity is rarely investigated. The specialized gut symbiont Snodgrassella alvi has codiversified with honeybees (Apis mellifera) and bumblebees (Bombus) for millions of years. Snodgrassella alvi strains are nearly identical for 16S rRNA gene sequences but have distinct gene repertoires potentially affecting host biology and community interactions. We examined S. alvi strain diversity within and between hosts using deep sequencing both of a single-copy coding gene (minD) and of the V4 region of the 16S rRNA gene. We sampled workers from domestic and feral A. mellifera colonies and wild-caught Bombus representing 14 species. Conventional analyses of community profiles, based on the V4 region of the 16S rRNA gene, failed to expose most strain variation. In contrast, the minD analysis revealed extensive strain variation within and between host species and individuals. Snodgrassella alvi strain diversity is significantly higher in A. mellifera than in Bombus, supporting the hypothesis that colony founding by swarms of workers enables retention of more diversity than colony founding by a single queen. Most Bombus individuals (72%) are dominated by a single S. alvi strain, whereas most A. mellifera (86%) possess multiple strains. No S. alvi strains are shared between A. mellifera and Bombus, indicating some host specificity. Among Bombus-restricted strains, some are restricted to a single host species or subgenus, while others occur in multiple subgenera. Findings demonstrate that strains diversify both within and between host species and can be highly specific or relatively generalized in their host associations. © 2016 John Wiley & Sons Ltd.

Within-host evolution versus immigration as a determinant of Escherichia coli diversity in the human gastrointestinal tract.

PubMed

Dixit, Ojas V A; O'Brien, Claire L; Pavli, Paul; Gordon, David M

2018-03-01

When a human host harbors two or more strains of Escherichia coli, the second strain is more likely to be a member of the same phylogroup rather than a different phylogroup. This outcome may be the consequence of a within host evolution event or an independent immigration/establishment event. To determine the relative importance of these two events in determining E. coli diversity in a host, a collection of multiple E. coli isolates recovered from each of 67 patients undergoing colonoscopies was used. Whole genome sequence data were available for one example of every REP-fingerprint type identified in a patient. Sequence type (ST) and single-nucleotide polymorphism (SNP) analyses revealed that 83% of strains observed in the host population were a consequence of immigration/establishment events. Restricting the analysis to hosts harboring two or more strains belonging to the same phylogroup revealed that in about half of these cases, the presence of a second strain belonging to the same phylogroup was the consequence of an independent immigration/establishment event. Thus, the results of this study show that despite hosts being exposed to a diversity of E. coli via their food, factors related to the host also determine what E. coli strains succeed in establishing. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

φX-174 Bacteriophage Structural Mutants Which Affect Deoxyribonucleic Acid Synthesis

PubMed Central

Siegel, Jeff E. D.; Hayashi, Masaki

1969-01-01

Seven cistrons in φX-174 were identified and one in particular was studied intensively: cistron A, which is assigned a protein in the mature phage. Amber mutants in this cistron synthesize a new deoxyribonucleic acid (DNA) form in addition to circular phage DNA upon infection of the restrictive host. This DNA is linear, non-infectious, and single-stranded; it is formed from the phage strand of replicative form φX-174 DNA. These mutants produce two different defective particles in the restrictive host. One particle contains circular phage DNA but is not infectious; the other contains the new DNA form and is similar to the 70S particles found in wild-type phage lysates. The mutant A gene product acts independently of normal A protein upon mixed infection of the restrictive host with an A mutant and a mutant from any other cistron or wild type. PMID:5823229

Unraveling the Host Plant Alternation of Cacopsylla pruni – Adults but Not Nymphs Can Survive on Conifers Due to Phloem/Xylem Composition

PubMed Central

Gallinger, Jannicke; Gross, Jürgen

2018-01-01

Plant sap feeding insects like psyllids are known to be vectors of phloem dwelling bacteria (‘Candidatus Phytoplasma’ and ‘Ca. Liberibacter’), plant pathogens which cause severe diseases and economically important crop damage. Some univoltine psyllid species have a particular life cycle, within one generation they alternate two times between different host plant species. The plum psyllid Cacopsylla pruni, the vector of European Stone Fruit Yellows (ESFY), one of the most serious pests in European fruit production, migrates to stone fruit orchards (Prunus spp.) for mating and oviposition in early spring. The young adults of the new generation leave the Prunus trees in summer and emigrate to their overwintering hosts like spruce and other conifers. Very little is known about the factors responsible for the regulation of migration, reasons for host alternation, and the behavior of psyllids during their phase of life on conifers. Because insect feeding behavior and host acceptance is driven by different biotic factors, such as olfactory and gustatory cues as well as mechanical barriers, we carried out electrical penetration graph (EPG) recordings and survival bioassays with C. pruni on different conifer species as potential overwintering hosts and analyzed the chemical composition of the respective plant saps. We are the first to show that migrating psyllids do feed on overwintering hosts and that nymphs are able to ingest phloem and xylem sap of coniferous trees, but cannot develop on conifer diet. Analyses of plant saps reveal qualitative differences in the chemical composition between coniferous trees and Prunus as well as within conifer species. These differences are discussed with regard to nutritional needs of psyllid nymphs for proper development, overwintering needs of adults and restriction of ‘Ca. P. prunorum’ to Prunus phloem. PMID:29706983

Spatial distribution of Echinococcus multilocularis, Svalbard, Norway.

PubMed

Fuglei, Eva; Stien, Audun; Yoccoz, Nigel G; Ims, Rolf A; Eide, Nina E; Prestrud, Pål; Deplazes, Peter; Oksanen, Antti

2008-01-01

In Svalbard, Norway, the only intermediate host for Echinococcus multilocularis, the sibling vole, has restricted spatial distribution. A survey of feces from the main host, the arctic fox, showed that only the area occupied by the intermediate host is associated with increased risk for human infection.

Melon chlorotic leaf curl virus: characterization and differential reassortment with closest relatives reveal adaptive virulence in the squash leaf curl virus clade and host shifting by the host-restricted bean calico mosaic virus.

PubMed

Idris, A M; Mills-Lujan, K; Martin, K; Brown, J K

2008-02-01

The genome components of the Melon chlorotic leaf curl virus (MCLCuV) were cloned from symptomatic cantaloupe leaves collected in Guatemala during 2002. The MCLCuV DNA-A and DNA-B components shared their closest nucleotide identities among begomoviruses, at approximately 90 and 81%, respectively, with a papaya isolate of MCLCuV from Costa Rica. The closest relatives at the species level were other members of the Squash leaf curl virus (SLCV) clade, which is endemic in the southwestern United States and Mexico. Biolistic inoculation of cantaloupe seedlings with the MCLCuV DNA-A and -B components resulted in the development of characteristic disease symptoms, providing definitive evidence of causality. MCLCuV experimentally infected species within the Cucurbitaceae, Fabaceae, and Solanaceae. The potential for interspecific reassortment was examined for MCLCuV and its closest relatives, including the bean-restricted Bean calico mosaic virus (BCaMV), and three other cucurbit-infecting species, Cucurbit leaf crumple virus (CuLCrV), SLCV, and SMLCV. The cucurbit viruses have distinct but overlapping host ranges. All possible reassortants were established using heterologous combinations of the DNA-A or DNA-B components. Surprisingly, only certain reassortants arising from MCLCuV and BCaMV, or MCLCuV and CuLCrV, were viable in bean, even though it is a host of all of the "wild-type" (parent) viruses. The bean-restricted BCaMV was differentially assisted in systemically infecting the cucurbit test species by the components of the four cucurbit-adapted begomoviruses. In certain heterologous combinations, the BCaMV DNA-A or -B component was able to infect one or more cucurbit species. Generally, the reassortants were less virulent in the test hosts than the respective wild-type (parent) viruses, strongly implicating adaptive modulation of virulence. This is the first illustration of reassortment resulting in the host range expansion of a host-restricted begomovirus.

The MHC-II transactivator CIITA, a restriction factor against oncogenic HTLV-1 and HTLV-2 retroviruses: similarities and differences in the inhibition of Tax-1 and Tax-2 viral transactivators

PubMed Central

Forlani, Greta; Abdallah, Rawan; Accolla, Roberto S.; Tosi, Giovanna

2013-01-01

The activation of CD4+ T helper cells is strictly dependent on the presentation of antigenic peptides by MHC class II (MHC-II) molecules. MHC-II expression is primarily regulated at the transcriptional level by the AIR-1 gene product CIITA (class II transactivator). Thus, CIITA plays a pivotal role in the triggering of the adaptive immune response against pathogens. Besides this well known function, we recently found that CIITA acts as an endogenous restriction factor against HTLV-1 (human T cell lymphotropic virus type 1) and HTLV-2 oncogenic retroviruses by targeting their viral transactivators Tax-1 and Tax-2, respectively. Here we review our findings on CIITA-mediated inhibition of viral replication and discuss similarities and differences in the molecular mechanisms by which CIITA specifically counteracts the function of Tax-1 and Tax-2 molecules. The dual function of CIITA as a key regulator of adaptive and intrinsic immunity represents a rather unique example of adaptation of host-derived factors against pathogen infections during evolution. PMID:23986750

Host Range Restriction of Insect-Specific Flaviviruses Occurs at Several Levels of the Viral Life Cycle.

PubMed

Junglen, Sandra; Korries, Marvin; Grasse, Wolfgang; Wieseler, Janett; Kopp, Anne; Hermanns, Kyra; León-Juárez, Moises; Drosten, Christian; Kümmerer, Beate Mareike

2017-01-01

The genus Flavivirus contains emerging arthropod-borne viruses (arboviruses) infecting vertebrates, as well as insect-specific viruses (ISVs) (i.e., viruses whose host range is restricted to insects). ISVs are evolutionary precursors to arboviruses. Knowledge of the nature of the ISV infection block in vertebrates could identify functions necessary for the expansion of the host range toward vertebrates. Mapping of host restrictions by complementation of ISV and arbovirus genome functions could generate knowledge critical to predicting arbovirus emergence. Here we isolated a novel flavivirus, termed Niénokoué virus (NIEV), from mosquitoes sampled in Côte d'Ivoire. NIEV groups with insect-specific flaviviruses (ISFs) in phylogeny and grows in insect cells but not in vertebrate cells. We generated an infectious NIEV cDNA clone and a NIEV reporter replicon to study growth restrictions of NIEV in comparison to yellow fever virus (YFV), for which the same tools are available. Efficient RNA replication of the NIEV reporter replicon was observed in insect cells but not in vertebrate cells. Initial translation of the input replicon RNA in vertebrate cells was functional, but RNA replication did not occur. Chimeric YFV carrying the envelope proteins of NIEV was recovered via electroporation in C6/36 insect cells but did not infect vertebrate cells, indicating a block at the level of entry. Since the YF/NIEV chimera readily produced infectious particles in insect cells but not in vertebrate cells despite efficient RNA replication, restriction is also determined at the level of assembly/release. Taking the results together, the ability of ISF to infect vertebrates is blocked at several levels, including attachment/entry and RNA replication as well as assembly/release. IMPORTANCE Most viruses of the genus Flavivirus , e.g., YFV and dengue virus, are mosquito borne and transmitted to vertebrates during blood feeding of mosquitoes. Within the last decade, an increasing number of viruses with a host range exclusively restricted to insects in close relationship to the vertebrate-pathogenic flaviviruses were discovered in mosquitoes. To identify barriers that could block the arboviral vertebrate tropism, we set out to identify the steps at which the ISF replication cycle fails in vertebrates. Our studies revealed blocks at several levels, suggesting that flavivirus host range expansion from insects to vertebrates was a complex process that involved overcoming multiple barriers.

Host Range Restriction of Insect-Specific Flaviviruses Occurs at Several Levels of the Viral Life Cycle

PubMed Central

Junglen, Sandra; Korries, Marvin; Grasse, Wolfgang; Wieseler, Janett; Kopp, Anne; Hermanns, Kyra; León-Juárez, Moises; Drosten, Christian

2017-01-01

ABSTRACT The genus Flavivirus contains emerging arthropod-borne viruses (arboviruses) infecting vertebrates, as well as insect-specific viruses (ISVs) (i.e., viruses whose host range is restricted to insects). ISVs are evolutionary precursors to arboviruses. Knowledge of the nature of the ISV infection block in vertebrates could identify functions necessary for the expansion of the host range toward vertebrates. Mapping of host restrictions by complementation of ISV and arbovirus genome functions could generate knowledge critical to predicting arbovirus emergence. Here we isolated a novel flavivirus, termed Niénokoué virus (NIEV), from mosquitoes sampled in Côte d’Ivoire. NIEV groups with insect-specific flaviviruses (ISFs) in phylogeny and grows in insect cells but not in vertebrate cells. We generated an infectious NIEV cDNA clone and a NIEV reporter replicon to study growth restrictions of NIEV in comparison to yellow fever virus (YFV), for which the same tools are available. Efficient RNA replication of the NIEV reporter replicon was observed in insect cells but not in vertebrate cells. Initial translation of the input replicon RNA in vertebrate cells was functional, but RNA replication did not occur. Chimeric YFV carrying the envelope proteins of NIEV was recovered via electroporation in C6/36 insect cells but did not infect vertebrate cells, indicating a block at the level of entry. Since the YF/NIEV chimera readily produced infectious particles in insect cells but not in vertebrate cells despite efficient RNA replication, restriction is also determined at the level of assembly/release. Taking the results together, the ability of ISF to infect vertebrates is blocked at several levels, including attachment/entry and RNA replication as well as assembly/release. IMPORTANCE Most viruses of the genus Flavivirus, e.g., YFV and dengue virus, are mosquito borne and transmitted to vertebrates during blood feeding of mosquitoes. Within the last decade, an increasing number of viruses with a host range exclusively restricted to insects in close relationship to the vertebrate-pathogenic flaviviruses were discovered in mosquitoes. To identify barriers that could block the arboviral vertebrate tropism, we set out to identify the steps at which the ISF replication cycle fails in vertebrates. Our studies revealed blocks at several levels, suggesting that flavivirus host range expansion from insects to vertebrates was a complex process that involved overcoming multiple barriers. PMID:28101536

Selfish restriction modification genes: resistance of a resident R/M plasmid to displacement by an incompatible plasmid mediated by host killing.

PubMed

Naito, Y; Naito, T; Kobayashi, I

1998-01-01

Previous work from this laboratory demonstrated that plasmids carrying a type II restriction-modification gene complex are not easily lost from their bacterial host because plasmid-free segregant cells are killed through chromosome cleavage. Here, we have followed the course of events that takes place when an Escherichia coli rec BC sbcA strain carrying a plasmid coding for the PaeR7I restriction-modification (R/M) gene complex is transformed by a plasmid with an identical origin of replication. The number of transformants that appeared was far fewer than with the restriction-minus (r-) control. Most of the transformants were very small. After prolonged incubation, the number and the size of the colonies increased, but this increase never attained the level of the r- control. Most of the transformed colonies retained the drug-resistance of the resident, r+ m+ plasmid. These results indicate that post-segregational host killing occurs when a plasmid bearing an R/M gene complex is displaced by an incompatible plasmid. Such cell killing eliminates the competitor plasmid along with the host and, thus, would allow persistence of the R/M plasmid in the neighboring, clonal host cells in nature. This phenomenon is reminiscent of mammalian apoptosis and other forms of altruistic cell death strategy against infection. This type of resistance to displacement was also studied in a wild type Escherichia coli strain that was normal for homologous recombination (rec+). A number of differences between the recBC sbcA strain and the rec+ strain were observed and these will be discussed.

Genomic Evidence for the Evolution of Streptococcus equi: Host Restriction, Increased Virulence, and Genetic Exchange with Human Pathogens

PubMed Central

Paillot, Romain; Steward, Karen F.; Webb, Katy; Ainslie, Fern; Jourdan, Thibaud; Bason, Nathalie C.; Holroyd, Nancy E.; Mungall, Karen; Quail, Michael A.; Sanders, Mandy; Simmonds, Mark; Willey, David; Brooks, Karen; Aanensen, David M.; Spratt, Brian G.; Jolley, Keith A.; Maiden, Martin C. J.; Kehoe, Michael; Chanter, Neil; Bentley, Stephen D.; Robinson, Carl; Maskell, Duncan J.; Parkhill, Julian; Waller, Andrew S.

2009-01-01

The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi) is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus). These pathogens share approximately 80% genome sequence identity with the important human pathogen Streptococcus pyogenes. We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen. Our analysis provides evidence of functional loss due to mutation and deletion, coupled with pathogenic specialization through the acquisition of bacteriophage encoding a phospholipase A2 toxin, and four superantigens, and an integrative conjugative element carrying a novel iron acquisition system with similarity to the high pathogenicity island of Yersinia pestis. We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution. We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci. PMID:19325880

HIV-1 Vpu Antagonizes CD317/Tetherin by Adaptor Protein-1-Mediated Exclusion from Virus Assembly Sites

PubMed Central

Pujol, François M.; Laketa, Vibor; Schmidt, Florian; Mukenhirn, Markus; Müller, Barbara; Boulant, Steeve; Grimm, Dirk; Keppler, Oliver T.

2016-01-01

ABSTRACT The host cell restriction factor CD317/tetherin traps virions at the surface of producer cells to prevent their release. The HIV-1 accessory protein Vpu antagonizes this restriction. Vpu reduces the cell surface density of the restriction factor and targets it for degradation; however, these activities are dispensable for enhancing particle release. Instead, Vpu has been suggested to antagonize CD317/tetherin by preventing recycling of internalized CD317/tetherin to the cell surface, blocking anterograde transport of newly synthesized CD317/tetherin, and/or displacing the restriction factor from virus assembly sites at the plasma membrane. At the molecular level, antagonism relies on the physical interaction of Vpu with CD317/tetherin. Recent findings suggested that phosphorylation of a diserine motif enables Vpu to bind to adaptor protein 1 (AP-1) trafficking complexes via two independent interaction motifs and to couple CD317/tetherin to the endocytic machinery. Here, we used a panel of Vpu proteins with specific mutations in individual interaction motifs to define which interactions are required for antagonism of CD317/tetherin. Impairing recycling or anterograde transport of CD317/tetherin to the plasma membrane was insufficient for antagonism. In contrast, excluding CD317/tetherin from HIV-1 assembly sites depended on Vpu motifs for interaction with AP-1 and CD317/tetherin and correlated with antagonism of the particle release restriction. Consistently, interference with AP-1 function or its expression blocked these Vpu activities. Our results define displacement from HIV-1 assembly sites as active principle of CD317/tetherin antagonism by Vpu and support a role of tripartite complexes between Vpu, AP-1, and CD317/tetherin in this process. IMPORTANCE CD317/tetherin poses an intrinsic barrier to human immunodeficiency virus type 1 (HIV-1) replication in human cells by trapping virus particles at the surface of producer cells and thereby preventing their release. The viral protein Vpu antagonizes this restriction, and molecular interactions with the restriction factor and adaptor protein complex 1 (AP-1) were suggested to mediate this activity. Vpu modulates intracellular trafficking of CD317/tetherin and excludes the restriction factor from HIV-1 assembly sites at the plasma membrane, but the relative contribution of these effects to antagonism remain elusive. Using a panel of Vpu mutants, as well as interference with AP-1 function and expression, we show here that Vpu antagonizes CD317/tetherin by blocking its recruitment to viral assembly sites in an AP-1-dependent manner. These results refine our understanding of the molecular mechanisms of CD317/tetherin antagonism and suggest complexes of Vpu with the restriction factor and AP-1 as targets for potential therapeutic intervention. PMID:27170757

THE E1 PROTEINS

PubMed Central

Bergvall, Monika; Melendy, Thomas; Archambault, Jacques

2013-01-01

E1, an ATP-dependent DNA helicase, is the only enzyme encoded by papillomaviruses (PVs). It is essential for replication and amplification of the viral episome in the nucleus of infected cells. To do so, E1 assembles into a double-hexamer at the viral origin, unwinds DNA at the origin and ahead of the replication fork and interacts with cellular DNA replication factors. Biochemical and structural studies have revealed the assembly pathway of E1 at the origin and how the enzyme unwinds DNA using a spiral escalator mechanism. E1 is tightly regulated in vivo, in particular by post-translational modifications that restrict its accumulation in the nucleus. Here we review how different functional domains of E1 orchestrate viral DNA replication, with an emphasis on their interactions with substrate DNA, host DNA replication factors and modifying enzymes. These studies have made E1 one of the best characterized helicases and provided unique insights on how PVs usurp different host-cell machineries to replicate and amplify their genome in a tightly controlled manner. PMID:24029589

Indication for Co-evolution of Lactobacillus johnsonii with its hosts

PubMed Central

2012-01-01

Background The intestinal microbiota, composed of complex bacterial populations, is host-specific and affected by environmental factors as well as host genetics. One important bacterial group is the lactic acid bacteria (LAB), which include many health-promoting strains. Here, we studied the genetic variation within a potentially probiotic LAB species, Lactobacillus johnsonii, isolated from various hosts. Results A wide survey of 104 fecal samples was carried out for the isolation of L. johnsonii. As part of the isolation procedure, terminal restriction fragment length polymorphism (tRFLP) was performed to identify L. johnsonii within a selected narrow spectrum of fecal LAB. The tRFLP results showed host specificity of two bacterial species, the Enterococcus faecium species cluster and Lactobacillus intestinalis, to different host taxonomic groups while the appearance of L. johnsonii and E. faecalis was not correlated with any taxonomic group. The survey ultimately resulted in the isolation of L. johnsonii from few host species. The genetic variation among the 47 L. johnsonii strains isolated from the various hosts was analyzed based on variation at simple sequence repeats (SSR) loci and multi-locus sequence typing (MLST) of conserved hypothetical genes. The genetic relationships among the strains inferred by each of the methods were similar, revealing three different clusters of L. johnsonii strains, each cluster consisting of strains from a different host, i.e. chickens, humans or mice. Conclusions Our typing results support phylogenetic separation of L. johnsonii strains isolated from different animal hosts, suggesting specificity of L. johnsonii strains to their hosts. Taken together with the tRFLP results, that indicated the association of specific LAB species with the host taxonomy, our study supports co-evolution of the host and its intestinal lactic acid bacteria. PMID:22827843

Indication for Co-evolution of Lactobacillus johnsonii with its hosts.

PubMed

Buhnik-Rosenblau, Keren; Matsko-Efimov, Vera; Jung, Minju; Shin, Heuynkil; Danin-Poleg, Yael; Kashi, Yechezkel

2012-07-25

The intestinal microbiota, composed of complex bacterial populations, is host-specific and affected by environmental factors as well as host genetics. One important bacterial group is the lactic acid bacteria (LAB), which include many health-promoting strains. Here, we studied the genetic variation within a potentially probiotic LAB species, Lactobacillus johnsonii, isolated from various hosts. A wide survey of 104 fecal samples was carried out for the isolation of L. johnsonii. As part of the isolation procedure, terminal restriction fragment length polymorphism (tRFLP) was performed to identify L. johnsonii within a selected narrow spectrum of fecal LAB. The tRFLP results showed host specificity of two bacterial species, the Enterococcus faecium species cluster and Lactobacillus intestinalis, to different host taxonomic groups while the appearance of L. johnsonii and E. faecalis was not correlated with any taxonomic group. The survey ultimately resulted in the isolation of L. johnsonii from few host species. The genetic variation among the 47 L. johnsonii strains isolated from the various hosts was analyzed based on variation at simple sequence repeats (SSR) loci and multi-locus sequence typing (MLST) of conserved hypothetical genes. The genetic relationships among the strains inferred by each of the methods were similar, revealing three different clusters of L. johnsonii strains, each cluster consisting of strains from a different host, i.e. chickens, humans or mice. Our typing results support phylogenetic separation of L. johnsonii strains isolated from different animal hosts, suggesting specificity of L. johnsonii strains to their hosts. Taken together with the tRFLP results, that indicated the association of specific LAB species with the host taxonomy, our study supports co-evolution of the host and its intestinal lactic acid bacteria.

Host range phenotype induced by mutations in the internal ribosomal entry site of poliovirus RNA.

PubMed Central

Shiroki, K; Ishii, T; Aoki, T; Ota, Y; Yang, W X; Komatsu, T; Ami, Y; Arita, M; Abe, S; Hashizume, S; Nomoto, A

1997-01-01

Most poliovirus strains infect only primates. The host range (HR) of poliovirus is thought to be primarily determined by a cell surface molecule that functions as poliovirus receptor (PVR), since it has been shown that transgenic mice are made poliovirus sensitive by introducing the human PVR gene into the genome. The relative levels of neurovirulence of polioviruses tested in these transgenic mice were shown to correlate well with the levels tested in monkeys (H. Horie et al., J. Virol. 68:681-688, 1994). Mutants of the virulent Mahoney strain of poliovirus have been generated by disruption of nucleotides 128 to 134, at stem-loop II within the 5' noncoding region, and four of these mutants multiplicated well in human HeLa cells but poorly in mouse TgSVA cells that had been established from the kidney of the poliovirus-sensitive transgenic mouse. Neurovirulence tests using the two animal models revealed that these mutants were strongly attenuated only in tests with the mouse model and were therefore HR mutants. The virus infection cycle in TgSVA cells was restricted by an internal ribosomal entry site (IRES)-dependent initiation process of translation. Viral protein synthesis and the associated block of cellular protein synthesis were not observed in TgSVA cells infected with three of four HR mutants and was evident at only a low level in the remaining mutant. The mutant RNAs were functional in a cell-free protein synthesis system from HeLa cells but not in those from TgSVA and mouse neuroblastoma NS20Y cells. These results suggest that host factor(s) affecting IRES-dependent translation of poliovirus differ between human and mouse cells and that the mutant IRES constructs detect species differences in such host factor(s). The IRES could potentially be a host range determinant for poliovirus infection. PMID:8985316

DOE Office of Scientific and Technical Information (OSTI.GOV)

Na, Lei; Tang, Yan-Dong; Biotechnology Institute of Southern Medical University, Guangzhou 510515

Highlights: • TRIMe7-CypA expresses in rhesus and pig-tailed, but not long-tailed macaques. • TRIMe7-CypA does not show the restriction to a HIV-GFP report virus in vitro. • It acts as a negative modulator to TRIM5α likely by competitive inhibition. - Abstract: The existence of innate, host-specific restriction factors is a major obstacle to the development of nonhuman primate models for AIDS studies, and TRIM5α is one of the most important of these restriction factors. In recent years, a TRIM5 chimeric gene that was retrotransposed by a cyclophilin A (CypA) cDNA was identified in certain macaque species. The TRIM5α-CypA fusion protein,more » TRIMCyp, which was expressed in these monkeys, had lost its restriction ability toward HIV-1. We previously found that TRIMe7-CypA, an alternative splicing isoform of the TRIMCyp transcripts, was expressed in pig-tailed and rhesus macaques but absent in long-tailed macaques. In this study, the anti-HIV-1 activity of TRIMe7-CypA in the rhesus macaque (RhTRIMe7-CypA) was investigated. The over-expression of RhTRIMe7-CypA in CrFK, HeLa and HEK293T cells did not restrict the infection or replication of an HIV-1-GFP reporter virus in these cells. As a positive control, rhesus (rh)TRIM5α strongly inhibited the reporter virus. Intriguingly, the anti-HIV-1 activity of RhTRIM5α was significantly reduced in a dose-dependent manner by the co-repression of RhTRIMe7-CypA. Our data indicate that although the RhTRIMe7-CypA isoform does not appear to restrict HIV-1, it may act as a negative modulator of TRIM family proteins, presumably by competitive inhibition.« less

Phenotypic plasticity and similarity among gall morphotypes on a superhost, Baccharis reticularia (Asteraceae).

PubMed

Formiga, A T; Silveira, F A O; Fernandes, G W; Isaias, R M S

2015-03-01

Understanding factors that modulate plant development is still a challenging task in plant biology. Although research has highlighted the role of abiotic and biotic factors in determining final plant structure, we know little of how these factors combine to produce specific developmental patterns. Here, we studied patterns of cell and tissue organisation in galled and non-galled organs of Baccharis reticularia, a Neotropical shrub that hosts over ten species of galling insects. We employed qualitative and quantitative approaches to understand patterns of growth and differentiation in its four most abundant gall morphotypes. We compared two leaf galls induced by sap-sucking Hemiptera and stem galls induced by a Lepidopteran and a Dipteran, Cecidomyiidae. The hypotheses tested were: (i) the more complex the galls, the more distinct they are from their non-galled host; (ii) galls induced on less plastic host organs, e.g. stems, develop under more morphogenetic constraints and, therefore, should be more similar among themselves than galls induced on more plastic organs. We also evaluated the plant sex preference of gall-inducing insects for oviposition. Simple galls were qualitative and quantitatively more similar to non-galled organs than complex galls, thereby supporting the first hypothesis. Unexpectedly, stem galls had more similarities between them than to their host organ, hence only partially supporting the second hypothesis. Similarity among stem galls may be caused by the restrictive pattern of host stems. The opposite trend was observed for host leaves, which generate either similar or distinct gall morphotypes due to their higher phenotypic plasticity. The Relative Distance of Plasticity Index for non-galled stems and stem galls ranged from 0.02 to 0.42. Our results strongly suggest that both tissue plasticity and gall inducer identity interact to determine plant developmental patterns, and therefore, final gall structure. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Human cytomegalovirus tegument protein pp150 acts as a cyclin A2-CDK-dependent sensor of the host cell cycle and differentiation state.

PubMed

Bogdanow, Boris; Weisbach, Henry; von Einem, Jens; Straschewski, Sarah; Voigt, Sebastian; Winkler, Michael; Hagemeier, Christian; Wiebusch, Lüder

2013-10-22

Upon cell entry, herpesviruses deliver a multitude of premade virion proteins to their hosts. The interplay between these incoming proteins and cell-specific regulatory factors dictates the outcome of infections at the cellular level. Here, we report a unique type of virion-host cell interaction that is essential for the cell cycle and differentiation state-dependent onset of human cytomegalovirus (HCMV) lytic gene expression. The major tegument 150-kDa phosphoprotein (pp150) of HCMV binds to cyclin A2 via a functional RXL/Cy motif resulting in its cyclin A2-dependent phosphorylation. Alanine substitution of the RXL/Cy motif prevents this interaction and allows the virus to fully escape the cyclin-dependent kinase (CDK)-mediated block of immediate early (IE) gene expression in S/G2 phase that normally restricts the onset of the HCMV replication cycle to G0/G1. Furthermore, the cyclin A2-CDK-pp150 axis is also involved in the establishment of HCMV quiescence in NTera2 cells, showing the importance of this molecular switch for differentiation state-dependent regulation of IE gene expression. Consistent with the known nucleocapsid-binding function of pp150, its RXL/Cy-dependent phosphorylation affects gene expression of the parental virion only, suggesting a cis-acting, virus particle-associated mechanism of control. The pp150 homologs of other primate and mammalian CMVs lack an RXL/Cy motif and accordingly even the nearest relative of HCMV, chimpanzee CMV, starts its lytic cycle in a cell cycle-independent manner. Thus, HCMV has evolved a molecular sensor for cyclin A2-CDK activity to restrict its IE gene expression program as a unique level of self-limitation and adaptation to its human host.

The missing link: Bordetella petrii is endowed with both the metabolic versatility of environmental bacteria and virulence traits of pathogenic Bordetellae.

PubMed

Gross, Roy; Guzman, Carlos A; Sebaihia, Mohammed; dos Santos, Vítor A P Martins; Pieper, Dietmar H; Koebnik, Ralf; Lechner, Melanie; Bartels, Daniela; Buhrmester, Jens; Choudhuri, Jomuna V; Ebensen, Thomas; Gaigalat, Lars; Herrmann, Stefanie; Khachane, Amit N; Larisch, Christof; Link, Stefanie; Linke, Burkhard; Meyer, Folker; Mormann, Sascha; Nakunst, Diana; Rückert, Christian; Schneiker-Bekel, Susanne; Schulze, Kai; Vorhölter, Frank-Jörg; Yevsa, Tetyana; Engle, Jacquelyn T; Goldman, William E; Pühler, Alfred; Göbel, Ulf B; Goesmann, Alexander; Blöcker, Helmut; Kaiser, Olaf; Martinez-Arias, Rosa

2008-09-30

Bordetella petrii is the only environmental species hitherto found among the otherwise host-restricted and pathogenic members of the genus Bordetella. Phylogenetically, it connects the pathogenic Bordetellae and environmental bacteria of the genera Achromobacter and Alcaligenes, which are opportunistic pathogens. B. petrii strains have been isolated from very different environmental niches, including river sediment, polluted soil, marine sponges and a grass root. Recently, clinical isolates associated with bone degenerative disease or cystic fibrosis have also been described. In this manuscript we present the results of the analysis of the completely annotated genome sequence of the B. petrii strain DSMZ12804. B. petrii has a mosaic genome of 5,287,950 bp harboring numerous mobile genetic elements, including seven large genomic islands. Four of them are highly related to the clc element of Pseudomonas knackmussii B13, which encodes genes involved in the degradation of aromatics. Though being an environmental isolate, the sequenced B. petrii strain also encodes proteins related to virulence factors of the pathogenic Bordetellae, including the filamentous hemagglutinin, which is a major colonization factor of B. pertussis, and the master virulence regulator BvgAS. However, it lacks all known toxins of the pathogenic Bordetellae. The genomic analysis suggests that B. petrii represents an evolutionary link between free-living environmental bacteria and the host-restricted obligate pathogenic Bordetellae. Its remarkable metabolic versatility may enable B. petrii to thrive in very different ecological niches.

The missing link: Bordetella petrii is endowed with both the metabolic versatility of environmental bacteria and virulence traits of pathogenic Bordetellae

PubMed Central

Gross, Roy; Guzman, Carlos A; Sebaihia, Mohammed; Martins dos Santos, Vítor AP; Pieper, Dietmar H; Koebnik, Ralf; Lechner, Melanie; Bartels, Daniela; Buhrmester, Jens; Choudhuri, Jomuna V; Ebensen, Thomas; Gaigalat, Lars; Herrmann, Stefanie; Khachane, Amit N; Larisch, Christof; Link, Stefanie; Linke, Burkhard; Meyer, Folker; Mormann, Sascha; Nakunst, Diana; Rückert, Christian; Schneiker-Bekel, Susanne; Schulze, Kai; Vorhölter, Frank-Jörg; Yevsa, Tetyana; Engle, Jacquelyn T; Goldman, William E; Pühler, Alfred; Göbel, Ulf B; Goesmann, Alexander; Blöcker, Helmut; Kaiser, Olaf; Martinez-Arias, Rosa

2008-01-01

Background Bordetella petrii is the only environmental species hitherto found among the otherwise host-restricted and pathogenic members of the genus Bordetella. Phylogenetically, it connects the pathogenic Bordetellae and environmental bacteria of the genera Achromobacter and Alcaligenes, which are opportunistic pathogens. B. petrii strains have been isolated from very different environmental niches, including river sediment, polluted soil, marine sponges and a grass root. Recently, clinical isolates associated with bone degenerative disease or cystic fibrosis have also been described. Results In this manuscript we present the results of the analysis of the completely annotated genome sequence of the B. petrii strain DSMZ12804. B. petrii has a mosaic genome of 5,287,950 bp harboring numerous mobile genetic elements, including seven large genomic islands. Four of them are highly related to the clc element of Pseudomonas knackmussii B13, which encodes genes involved in the degradation of aromatics. Though being an environmental isolate, the sequenced B. petrii strain also encodes proteins related to virulence factors of the pathogenic Bordetellae, including the filamentous hemagglutinin, which is a major colonization factor of B. pertussis, and the master virulence regulator BvgAS. However, it lacks all known toxins of the pathogenic Bordetellae. Conclusion The genomic analysis suggests that B. petrii represents an evolutionary link between free-living environmental bacteria and the host-restricted obligate pathogenic Bordetellae. Its remarkable metabolic versatility may enable B. petrii to thrive in very different ecological niches. PMID:18826580

3D Spatially Resolved Models of the Intracellular Dynamics of the Hepatitis C Genome Replication Cycle

PubMed Central

Reiter, Sebastian; Grillo, Alfio; Herrmann, Eva; Wittum, Gabriel

2017-01-01

Mathematical models of virus dynamics have not previously acknowledged spatial resolution at the intracellular level despite substantial arguments that favor the consideration of intracellular spatial dependence. The replication of the hepatitis C virus (HCV) viral RNA (vRNA) occurs within special replication complexes formed from membranes derived from endoplasmatic reticulum (ER). These regions, termed membranous webs, are generated primarily through specific interactions between nonstructural virus-encoded proteins (NSPs) and host cellular factors. The NSPs are responsible for the replication of the vRNA and their movement is restricted to the ER surface. Therefore, in this study we developed fully spatio-temporal resolved models of the vRNA replication cycle of HCV. Our simulations are performed upon realistic reconstructed cell structures—namely the ER surface and the membranous webs—based on data derived from immunostained cells replicating HCV vRNA. We visualized 3D simulations that reproduced dynamics resulting from interplay of the different components of our models (vRNA, NSPs, and a host factor), and we present an evaluation of the concentrations for the components within different regions of the cell. Thus far, our model is restricted to an internal portion of a hepatocyte and is qualitative more than quantitative. For a quantitative adaption to complete cells, various additional parameters will have to be determined through further in vitro cell biology experiments, which can be stimulated by the results described in the present study. PMID:28973992

Kaposi's Sarcoma-Associated Herpesvirus G-Protein-Coupled Receptor Prevents AU-Rich-Element-Mediated mRNA Decay

PubMed Central

Corcoran, Jennifer A.; Khaperskyy, Denys A.; Johnston, Benjamin P.; King, Christine A.; Cyr, David P.; Olsthoorn, Alisha V.

2012-01-01

During lytic Kaposi's sarcoma-associated herpesvirus (KSHV) infection, host gene expression is severely restricted by a process of global mRNA degradation known as host shutoff, which rededicates translational machinery to the expression of viral proteins. A subset of host mRNAs is spared from shutoff, and a number of these contain cis-acting AU-rich elements (AREs) in their 3′ untranslated regions. AREs are found in labile mRNAs encoding cytokines, growth factors, and proto-oncogenes. Activation of the p38/MK2 signal transduction pathway reverses constitutive decay of ARE-mRNAs, resulting in increased protein production. The viral G-protein-coupled receptor (vGPCR) is thought to play an important role in promoting the secretion of angiogenic molecules from KSHV-infected cells during lytic replication, but to date it has not been clear how vGPCR circumvents host shutoff. Here, we demonstrate that vGPCR activates the p38/MK2 pathway and stabilizes ARE-mRNAs, augmenting the levels of their protein products. Using MK2-deficient cells, we demonstrate that MK2 is essential for maximal vGPCR-mediated ARE-mRNA stabilization. ARE-mRNAs are normally delivered to cytoplasmic ribonucleoprotein granules known as processing bodies (PBs) for translational silencing and decay. We demonstrate that PB formation is prevented during KSHV lytic replication or in response to vGPCR-mediated activation of RhoA subfamily GTPases. Together, these data show for the first time that vGPCR impacts gene expression at the posttranscriptional level, coordinating an attack on the host mRNA degradation machinery. By suppressing ARE-mRNA turnover, vGPCR may facilitate escape of certain target mRNAs from host shutoff and allow secretion of angiogenic factors from lytically infected cells. PMID:22696654

The Well-Tempered SIV Infection: Pathogenesis of SIV Infection in Natural Hosts in the Wild, with Emphasis on Virus Transmission and Early Events Post-Infection that May Contribute to Protection from Disease Progression

PubMed Central

Raehtz, Kevin; Pandrea, Ivona; Apetrei, Cristian

2016-01-01

African NHPs are infected by over 40 different simian immunodeficiency viruses. These viruses have coevolved with their hosts for long periods of time and, unlike HIV in humans, infection does not generally lead to disease progression. Chronic viral replication is maintained for the natural lifespan of the host, without loss of overall immune function. Lack of disease progression is not correlated with transmission, as SIV infection is highly prevalent in many African NHP species in the wild. The exact mechanisms by which these natural hosts of SIV avoid disease progression are still unclear, but a number of factors might play a role, including: (i) avoidance of microbial translocation from the gut lumen by preventing or repairing damage to the gut epithelium; (ii) control of immune activation and apoptosis following infection; (iii) establishment of an anti-inflammatory response that resolves chronic inflammation; (iv) maintenance of homeostasis of various immune cell populations, including NK cells, monocytes/macrophages, dendritic cells, Tregs, Th17 T-cells, and γδ T-cells; (v) restriction of CCR5 availability at mucosal sites; (vi) preservation of T-cell function associated with down-regulation of CD4 receptor. Some of these mechanisms might also be involved in protection of natural hosts from mother-to-infant SIV transmission during breastfeeding. The difficulty of performing invasive studies in the wild has prohibited investigation of the exact events surrounding transmission in natural hosts. Increased understanding of the mechanisms of SIV transmission in natural hosts, and of the early events post-transmission which may contribute to avoidance of disease progression, along with better comprehension of the factors involved in protection from SIV breastfeeding transmission in the natural hosts, could prove invaluable for the development of new prevention strategies for HIV. PMID:27394696

Effects of energy restriction and wheel running on mammary carcinogenesis and host systemic factors in a rat model.

PubMed

Zhu, Zongjian; Jiang, Weiqin; Zacher, Jarrod H; Neil, Elizabeth S; McGinley, John N; Thompson, Henry J

2012-03-01

Limiting energy availability via diet or physical activity has health benefits; however, it is not known whether these interventions have similar effects on the development of cancer. Two questions were addressed as follows: (i) Does limiting energy availability by increasing physical activity have the same effect on mammary carcinogenesis as limiting caloric intake? and (ii) Are host systemic factors, implicated as risk biomarkers for breast cancer, similarly affected by these interventions? Female Sprague Dawley rats were injected with 50-mg 1-methyl-1-nitrosourea per kg body weight at 21 days of age and randomized to one of five groups (30 rats per group) as follows: (i) sham running wheel control; (ii) restricted fed to 85% of the sham control; (iii and iv) voluntary running in a motorized activity wheel (37 m/min) to a maximum of 3,500 m/d or 1,750 m/d; and (v) sedentary ad libitum fed control with no access to a running wheel. The three energetics interventions inhibited the carcinogenic response, reducing cancer incidence (P = 0.01), cancer multiplicity (P < 0.001), and cancer burden (P < 0.001) whereas prolonging cancer latency (P = 0.004) although differences among energetics interventions were not significant. Of the plasma biomarkers associated with the development of cancer, the energetics interventions reduced bioavailable insulin-like growth factor-1 (IGF-1), insulin, interleukin-6, serum amyloid protein, TNF-α, and leptin and increased IGF-binding protein 3 (IGFBP-3) and adiponectin. Plasma-fasting glucose, C-reactive protein, estradiol, and progesterone were unaffected. The plasma biomarkers of greatest value in predicting the carcinogenic response were adiponectin > IGF-1/IGFBP-3 > IGFBP-3 > leptin > IGF-1.

Analysis of Host Range Restriction Determinants in the Rabbit Model: Comparison of Homologous and Heterologous Rotavirus Infections

PubMed Central

Ciarlet, Max; Estes, Mary K.; Barone, Christopher; Ramig, Robert F.; Conner, Margaret E.

1998-01-01

The main limitation of both the rabbit and mouse models of rotavirus infection is that human rotavirus (HRV) strains do not replicate efficiently in either animal. The identification of individual genes necessary for conferring replication competence in a heterologous host is important to an understanding of the host range restriction of rotavirus infections. We recently reported the identification of the P type of the spike protein VP4 of four lapine rotavirus strains as being P[14]. To determine whether VP4 is involved in host range restriction in rabbits, we evaluated infection in rotavirus antibody-free rabbits inoculated orally with two P[14] HRVs, PA169 (G6) and HAL1166 (G8), and with several other HRV strains and animal rotavirus strains of different P and G types. We also evaluated whether the parental rhesus rotavirus (RRV) (P5B[3], G3) and the derived RRV-HRV reassortant candidate vaccine strains RRV × D (G1), RRV × DS-1 (G2), and RRV × ST3 (G4) would productively infect rabbits. Based on virus shedding, limited replication was observed with the P[14] HRV strains and with the SA11 Cl3 (P[2], G3) and SA11 4F (P6[1], G3) animal rotavirus strains, compared to the homologous ALA strain (P[14], G3). However, even limited infection provided complete protection from rotavirus infection when rabbits were challenged orally 28 days postinoculation (DPI) with 103 50% infective doses of ALA rabbit rotavirus. Other HRVs did not productively infect rabbits and provided no significant protection from challenge, in spite of occasional seroconversion. Simian RRV replicated as efficiently as lapine ALA rotavirus in rabbits and provided complete protection from ALA challenge. Live attenuated RRV reassortant vaccine strains resulted in no, limited, or productive infection of rabbits, but all rabbits were completely protected from heterotypic ALA challenge. The altered replication efficiency of the reassortants in rabbits suggests a role for VP7 in host range restriction. Also, our results suggest that VP4 may be involved in, but is not exclusively responsible for, host range restriction in the rabbit model. The replication efficiency of rotavirus in rabbits also is not controlled by the product of gene 5 (NSP1) alone, since a reassortant rotavirus with ALA gene 5 and all other genes from SA11 was more severely replication restricted than either parental rotavirus strain. PMID:9499095

Mating Compatibility and Restriction Analysis of Ganoderma Isolates from Oil Palm and Other Palm Hosts.

PubMed

Jing, Chan Jer; Seman, Idris Abu; Zakaria, Latiffah

2015-12-01

Mating compatibility and restriction analyses of Internal Transcribed Spacer (ITS) regions were performed to determine the relations between Ganoderma boninense, the most common species associated with basal stem rot in oil palm and Ganoderma isolates from infected oil palm, two ornamental palms, sealing wax palm (Cyrtostachys renda) and MacArthur palm (Ptychosperma macarthurii), an isolate from coconut stump (Cocos nucifera), Ganoderma miniatocinctum, Ganoderma zonatum and Ganoderma tornatum. The results showed that G. boninense was compatible with Ganoderma isolates from oil palm, G. miniatocinctum and G. zonatum, Ganoderma isolates from sealing wax palm, MacArthur palm and coconut stump. G. boninense was not compatible with G. tornatum. Therefore, the results suggested that the G. boninense, G. miniatocinctum, G. zonatum, and Ganoderma isolates from oil palm, ornamental palms and coconut stump could represent the same biological species. In performing a restriction analysis of the ITS regions, variations were observed in which five haplotypes were generated from the restriction patterns. An unweighted pair-group method with arithmetic averages (UPGMA) cluster analysis showed that all the Ganoderma isolates were grouped into five primary groups, and the similarity values of the isolates ranged from 97% to 100%. Thus, a restriction analysis of the ITS regions showed that G. boninense and the Ganoderma isolates from other palm hosts were closely related. On the basis of the mating compatibility test and the restriction analysis of the ITS regions performed in this study, a diverse group of Ganoderma species from oil palm and other palm hosts are closely related, except for G. tornatum and Ganoderma isolates from tea and rubber.

Mating Compatibility and Restriction Analysis of Ganoderma Isolates from Oil Palm and Other Palm Hosts

PubMed Central

Jing, Chan Jer; Seman, Idris Abu; Zakaria, Latiffah

2015-01-01

Mating compatibility and restriction analyses of Internal Transcribed Spacer (ITS) regions were performed to determine the relations between Ganoderma boninense, the most common species associated with basal stem rot in oil palm and Ganoderma isolates from infected oil palm, two ornamental palms, sealing wax palm (Cyrtostachys renda) and MacArthur palm (Ptychosperma macarthurii), an isolate from coconut stump (Cocos nucifera), Ganoderma miniatocinctum, Ganoderma zonatum and Ganoderma tornatum. The results showed that G. boninense was compatible with Ganoderma isolates from oil palm, G. miniatocinctum and G. zonatum, Ganoderma isolates from sealing wax palm, MacArthur palm and coconut stump. G. boninense was not compatible with G. tornatum. Therefore, the results suggested that the G. boninense, G. miniatocinctum, G. zonatum, and Ganoderma isolates from oil palm, ornamental palms and coconut stump could represent the same biological species. In performing a restriction analysis of the ITS regions, variations were observed in which five haplotypes were generated from the restriction patterns. An unweighted pair-group method with arithmetic averages (UPGMA) cluster analysis showed that all the Ganoderma isolates were grouped into five primary groups, and the similarity values of the isolates ranged from 97% to 100%. Thus, a restriction analysis of the ITS regions showed that G. boninense and the Ganoderma isolates from other palm hosts were closely related. On the basis of the mating compatibility test and the restriction analysis of the ITS regions performed in this study, a diverse group of Ganoderma species from oil palm and other palm hosts are closely related, except for G. tornatum and Ganoderma isolates from tea and rubber. PMID:26868709

Pseudomonas sax genes overcome aliphatic isothiocyanate-mediated non-host resistance in Arabidopsis

Treesearch

Jun Fan; Casey Crooks; Gary Creissen; Lionel Hill; Shirley Fairhurst; Peter Doerner; Chris Lamb

2011-01-01

Most plant-microbe interactions do not result in disease; natural products restrict non-host pathogens. We found that sulforaphane (4-methylsulfinylbutyl isothiocyanate), a natural product derived from aliphatic glucosinolates, inhibits growth in Arabidopsis of non-host Pseudomonas bacteria in planta. Multiple sax genes (saxCAB/F/D/G) were identified in Pseudomonas...

Host identity is a dominant driver of mycorrhizal fungal community composition during ecosystem development.

PubMed

Martínez-García, Laura B; Richardson, Sarah J; Tylianakis, Jason M; Peltzer, Duane A; Dickie, Ian A

2015-03-01

Little is known about the response of arbuscular mycorrhizal fungal communities to ecosystem development. We use a long-term soil chronosequence that includes ecosystem progression and retrogression to quantify the importance of host plant identity as a factor driving fungal community composition during ecosystem development. We identified arbuscular mycorrhizal fungi and plant species from 50 individual roots from each of 10 sites spanning 5-120 000 yr of ecosystem age using terminal restriction fragment length polymorphism (T-RFLP), Sanger sequencing and pyrosequencing. Arbuscular mycorrhizal fungal communities were highly structured by ecosystem age. There was strong niche differentiation, with different groups of operational taxonomic units (OTUs) being characteristic of early succession, ecosystem progression and ecosystem retrogression. Fungal alpha diversity decreased with ecosystem age, whereas beta diversity was high at early stages and lower in subsequent stages. A total of 39% of the variance in fungal communities was explained by host plant and site age, 29% of which was attributed to host and the interaction between host and site (24% and 5%, respectively). The strong response of arbuscular mycorrhizal fungi to ecosystem development appears to be largely driven by plant host identity, supporting the concept that plant and fungal communities are tightly coupled rather than independently responding to habitat. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Review of osteoimmunology and the host response in endodontic and periodontal lesions

PubMed Central

Graves, Dana T.; Oates, Thomas; Garlet, Gustavo P.

2011-01-01

Both lesions of endodontic origin and periodontal diseases involve the host response to bacteria and the formation of osteolytic lesions. Important for both is the upregulation of inflammatory cytokines that initiate and sustain the inflammatory response. Also important are chemokines that induce recruitment of leukocyte subsets and bone-resorptive factors that are largely produced by recruited inflammatory cells. However, there are differences also. Lesions of endodontic origin pose a particular challenge since that bacteria persist in a protected reservoir that is not readily accessible to the immune defenses. Thus, experiments in which the host response is inhibited in endodontic lesions tend to aggravate the formation of osteolytic lesions. In contrast, bacteria that invade the periodontium appear to be less problematic so that blocking arms of the host response tend to reduce the disease process. Interestingly, both lesions of endodontic origin and periodontitis exhibit inflammation that appears to inhibit bone formation. In periodontitis, the spatial location of the inflammation is likely to be important so that a host response that is restricted to a subepithelial space is associated with gingivitis, while a host response closer to bone is linked to bone resorption and periodontitis. However, the persistence of inflammation is also thought to be important in periodontitis since inflammation present during coupled bone formation may limit the capacity to repair the resorbed bone. PMID:21547019

MUC1-specific immune therapy generates a strong anti-tumor response in a MUC1-tolerant colon cancer model

PubMed Central

Mukherjee, P.; Pathangey, L.B.; Bradley, J.B.; Tinder, T.L.; Basu, G.D.; Akporiaye, E.T.; Gendler, S.J.

2007-01-01

A MUC1-based vaccine was used in a preclinical model of colon cancer. The trial was conducted in a MUC1-tolerant immune competent host injected with MC38 colon cancer cells expressing MUC1. The vaccine included: MHC class I-restricted MUC1 peptides, MHC class II-restricted pan helper peptide, unmethylated CpG oligodeoxynucleotide, and granulocyte macrophage-colony stimulating factor. Immunization was successful in breaking MUC1 self-tolerance, and in eliciting a robust anti-tumor response. The vaccine stimulated IFN-γ-producing CD4+ helper and CD8+ cytotoxic T cells against MUC1 and other undefined MC38 tumor antigens. In the prophylactic setting, immunization caused complete rejection of tumor cells, while in the therapeutic regimen, tumor burden was significantly reduced. PMID:17166639

MUC1-specific immune therapy generates a strong anti-tumor response in a MUC1-tolerant colon cancer model.

PubMed

Mukherjee, P; Pathangey, L B; Bradley, J B; Tinder, T L; Basu, G D; Akporiaye, E T; Gendler, S J

2007-02-19

A MUC1-based vaccine was used in a preclinical model of colon cancer. The trial was conducted in a MUC1-tolerant immune competent host injected with MC38 colon cancer cells expressing MUC1. The vaccine included: MHC class I-restricted MUC1 peptides, MHC class II-restricted pan-helper-peptide, unmethylated CpG oligodeoxynucleotide, and granulocyte macrophage-colony stimulating factor. Immunization was successful in breaking MUC1 self-tolerance, and in eliciting a robust anti-tumor response. The vaccine stimulated IFN-gamma-producing CD4(+) helper and CD8(+) cytotoxic T cells against MUC1 and other undefined MC38 tumor antigens. In the prophylactic setting, immunization caused complete rejection of tumor cells, while in the therapeutic regimen, tumor burden was significantly reduced.

Reproductive effort and seasonality associated with male-biased parasitism in Gracilinanus agilis (Didelphimorphia: Didelphidae) infected by Eimeria spp. (Apicomplexa: Eimeriidae) in the Brazilian cerrado.

PubMed

Strona, A L S; Levenhagem, M; Leiner, N O

2015-07-01

The aggregation of parasites among hosts is associated with differential host exposure and susceptibility to parasites, which varies according to host gender, body size, reproductive status and environmental factors. We evaluated the role of these factors on infestation by Eimeria spp. (Eimeriidae) in the agile gracile mouse opossum (Gracilinanus agilis), a semelparous didelphid inhabiting neotropical savannahs. Eimeria spp. abundance and prevalence among G. agilis were associated with the breeding status of individuals and to a lesser extent to climatic season, with both sexes presenting higher Eimeria spp. burdens during late breeding/wet season. On the other hand, male-biased parasitism was restricted to dry/mating season. We suggest that male spatial organization and diet may account for increased parasite burdens within this sex, although future studies should evaluate the role of physiological differences associated with androgen hormones. Finally, a rapid increase in Eimeria spp. loads among females during the late breeding/wet season seems associated with seasonal changes in susceptibility, due to breeding costs related to semelparity, and exposure to infective propagules, while male-die off seems to explain maintenance of higher Eimeria spp. burdens within this sex in the same period.

A sulfur host based on titanium monoxide@carbon hollow spheres for advanced lithium-sulfur batteries.

PubMed

Li, Zhen; Zhang, Jintao; Guan, Buyuan; Wang, Da; Liu, Li-Min; Lou, Xiong Wen David

2016-10-20

Lithium-sulfur batteries show advantages for next-generation electrical energy storage due to their high energy density and cost effectiveness. Enhancing the conductivity of the sulfur cathode and moderating the dissolution of lithium polysulfides are two key factors for the success of lithium-sulfur batteries. Here we report a sulfur host that overcomes both obstacles at once. With inherent metallic conductivity and strong adsorption capability for lithium-polysulfides, titanium monoxide@carbon hollow nanospheres can not only generate sufficient electrical contact to the insulating sulfur for high capacity, but also effectively confine lithium-polysulfides for prolonged cycle life. Additionally, the designed composite cathode further maximizes the lithium-polysulfide restriction capability by using the polar shells to prevent their outward diffusion, which avoids the need for chemically bonding all lithium-polysulfides on the surfaces of polar particles.

A sulfur host based on titanium monoxide@carbon hollow spheres for advanced lithium-sulfur batteries

NASA Astrophysics Data System (ADS)

Li, Zhen; Zhang, Jintao; Guan, Buyuan; Wang, Da; Liu, Li-Min; Lou, Xiong Wen (David)

2016-10-01

Lithium-sulfur batteries show advantages for next-generation electrical energy storage due to their high energy density and cost effectiveness. Enhancing the conductivity of the sulfur cathode and moderating the dissolution of lithium polysulfides are two key factors for the success of lithium-sulfur batteries. Here we report a sulfur host that overcomes both obstacles at once. With inherent metallic conductivity and strong adsorption capability for lithium-polysulfides, titanium monoxide@carbon hollow nanospheres can not only generate sufficient electrical contact to the insulating sulfur for high capacity, but also effectively confine lithium-polysulfides for prolonged cycle life. Additionally, the designed composite cathode further maximizes the lithium-polysulfide restriction capability by using the polar shells to prevent their outward diffusion, which avoids the need for chemically bonding all lithium-polysulfides on the surfaces of polar particles.

Ifit2 Is a Restriction Factor in Rabies Virus Pathogenicity.

PubMed

Davis, Benjamin M; Fensterl, Volker; Lawrence, Tessa M; Hudacek, Andrew W; Sen, Ganes C; Schnell, Matthias J

2017-09-01

Understanding the interactions between rabies virus (RABV) and individual host cell proteins is critical for the development of targeted therapies. Here we report that interferon-induced protein with tetratricopeptide repeats 2 (Ifit2), an interferon-stimulated gene (ISG) with possible RNA-binding capacity, is an important restriction factor for rabies virus. When Ifit2 was depleted, RABV grew more quickly in mouse neuroblastoma cells in vitro This effect was replicated in vivo , where Ifit2 knockout mice displayed a dramatically more severe disease phenotype than wild-type mice after intranasal inoculation of RABV. This increase in pathogenicity correlated to an increase in RABV mRNA and live viral load in the brain, as well as to an accelerated spread to brain regions normally affected by this RABV model. These results suggest that Ifit2 exerts its antiviral effect mainly at the level of viral replication, as opposed to functioning as a mechanism that restricts viral entry/egress or transports RABV particles through axons. IMPORTANCE Rabies is a fatal zoonotic disease with a nearly 100% case fatality rate. Although there are effective vaccines for rabies, this disease still takes the lives of about 50,000 people each year. Victims tend to be children living in regions without comprehensive medical infrastructure who present to health care workers too late for postexposure prophylaxis. The protein discussed in our report, Ifit2, is found to be an important restriction factor for rabies virus, acting directly or indirectly against viral replication. A more nuanced understanding of this interaction may reveal a step of a pathway or site at which the system could be exploited for the development of a targeted therapy. Copyright © 2017 American Society for Microbiology.

Fab-based inhibitors reveal ubiquitin independent functions for HIV Vif neutralization of APOBEC3 restriction factors

PubMed Central

Smith, Amber M.; Hultquist, Judd F.; Caretta Cartozo, Nathalie; Campbell, Melody G.; Burton, Lily; La Greca, Florencia; McGregor, Michael J.; Ta, Hai M.; Bartholomeeusen, Koen; Peterlin, B. Matija; Krogan, Nevan J.; Sevillano, Natalia

2018-01-01

The lentiviral protein Viral Infectivity Factor (Vif) counteracts the antiviral effects of host APOBEC3 (A3) proteins and contributes to persistent HIV infection. Vif targets A3 restriction factors for ubiquitination and proteasomal degradation by recruiting them to a multi-protein ubiquitin E3 ligase complex. Here, we describe a degradation-independent mechanism of Vif-mediated antagonism that was revealed through detailed structure-function studies of antibody antigen-binding fragments (Fabs) to the Vif complex. Two Fabs were found to inhibit Vif-mediated A3 neutralization through distinct mechanisms: shielding A3 from ubiquitin transfer and blocking Vif E3 assembly. Combined biochemical, cell biological and structural studies reveal that disruption of Vif E3 assembly inhibited A3 ubiquitination but was not sufficient to restore its packaging into viral particles and antiviral activity. These observations establish that Vif can neutralize A3 family members in a degradation-independent manner. Additionally, this work highlights the potential of Fabs as functional probes, and illuminates how Vif uses a multi-pronged approach involving both degradation dependent and independent mechanisms to suppress A3 innate immunity. PMID:29304101

Viral and Cellular Factors Involved in Phloem Transport of Plant Viruses

PubMed Central

Hipper, Clémence; Brault, Véronique; Ziegler-Graff, Véronique; Revers, Frédéric

2013-01-01

Phloem transport of plant viruses is an essential step in the setting-up of a complete infection of a host plant. After an initial replication step in the first cells, viruses spread from cell-to-cell through mesophyll cells, until they reach the vasculature where they rapidly move to distant sites in order to establish the infection of the whole plant. This last step is referred to as systemic transport, or long-distance movement, and involves virus crossings through several cellular barriers: bundle sheath, vascular parenchyma, and companion cells for virus loading into sieve elements (SE). Viruses are then passively transported within the source-to-sink flow of photoassimilates and are unloaded from SE into sink tissues. However, the molecular mechanisms governing virus long-distance movement are far from being understood. While most viruses seem to move systemically as virus particles, some viruses are transported in SE as viral ribonucleoprotein complexes (RNP). The nature of the cellular and viral factors constituting these RNPs is still poorly known. The topic of this review will mainly focus on the host and viral factors that facilitate or restrict virus long-distance movement. PMID:23745125

The Outer Membrane Protein A (OmpA) of Y. pestis promotes intracellular survival and virulence in mice

PubMed Central

Bartra, Sara Schesser; Gong, Xin; Lorica, Cherish D.; Jain, Chaitanya; Nair, Manoj K. M.; Schifferli, Dieter; Qian, Lianfen; Li, Zhongwei; Plano, Gregory V.; Schesser, Kurt

2011-01-01

The plague bacterium Yersinia pestis has a number of well-described strategies to protect itself from both host cells and soluble factors. In an effort to identify additional anti-host factors, we employed a transposon site hybridization (TraSH)-based approach to screen 105 Y. pestis mutants in an in vitro infection system. In addition to loci encoding various components of the well-characterized type III secretion system (T3SS), our screen unambiguously identified ompA as a pro-survival gene. We go on to show that an engineered Y. pestis ΔompA strain, as well as a ΔompA strain of the closely related pathogen Y. pseudotuberculosis, have fully functioning T3SSs but are specifically defective in surviving within macrophages. Additionally, the Y. pestis ΔompA strain was outcompeted by the wild-type strain in a mouse co-infection assay. Unlike in other bacterial pathogens in which OmpA can promote adherence, invasion, or serum resistance, the OmpA of Y. pestis is restricted to enhancing intracellular survival. Our data show that OmpA of the pathogenic Yersinia is a virulence factor on par with the T3SS. PMID:22023991

Modulation of B16-BL6 murine melanoma metastatic phenotype by tyrosine and phenylalanine restriction in the absence of host selection pressures.

PubMed

Elstad, C A; Meadows, G G

1993-01-01

We previously showed that restriction of tyrosine (Tyr) and phenylalanine (Phe) in vivo dramatically suppresses the metastatic phenotype of B16-BL6 (BL6) murine melanoma. Present results indicate a direct effect of Tyr and Phe restriction on the tumor in the absence of host selection pressures. Lung colonizing ability of BL6 is dramatically suppressed after one passage in vitro in media containing low levels of Tyr and Phe. This antimetastatic effect is immediate, stable for at least 5 in vitro passages in Tyr and Phe restricted media, and evident event after levels of Tyr and Phe are restored to normal. Heterogeneity for lung colonizing ability is suppressed, as evidence by fewer tumor colonies formed by clones following i.v. inoculation into mice fed normal diet. This suppression of BL6 metastatic phenotype is not due to differential clearance and retention in the lung or to decreased growth, but is specific for these two amino acids. As the mechanism(s) for the antitumor effects of Tyr and Phe restriction are detailed, the relevance of Tyr and Phe restriction as an early adjuvant to effective cancer treatment can be explored.

Restriction Fragment Length Polymorphism Analysis Reveals High Levels of Genetic Divergence Among the Light Organ Symbionts of Flashlight Fish.

PubMed

Wolfe, C J; Haygood, M G

1991-08-01

Restriction fragment length polymorphisms within the lux and 16S ribosomal RNA gene regions were used to compare unculturable bacterial light organ symbionts of several anomalopid fish species. The method of Nei and Li (1979) was used to calculate phylogenetic distance from the patterns of restriction fragment lengths of the luxA and 16S rRNA regions. Phylogenetic trees constructed from each distance matrix (luxA and 16S rDNA data) have similar branching orders. The levels of divergence among the symbionts, relative to other culturable luminous bacteria, suggests that the symbionts differ at the level of species among host fish genera. Symbiont relatedness and host geographic location do not seem to be correlated, and the symbionts do not appear to be strains of common, free-living, luminous bacteria. In addition, the small number of hybridizing fragments within the 16S rRNA region of the symbionts, compared with that of the free-living species, suggests a decrease in copy number of rRNA operons relative to free-living species. At this level of investigation, the symbiont phylogeny is consistent with the proposed phylogeny of the host fish family and suggests that each symbiont strain coevolved with its host fish species.

Predictors of host specificity among behavior-manipulating parasites.

PubMed

Fredensborg, B L

2014-07-01

A trade-off between resource-specialization and the breadth of the ecological niche is one of the most fundamental biological characteristics. A true generalist (Jack-of-all-trades) displays a broad ecological niche with little resource specialization while the opposite is true for a resource-specialist that has a restricted ecological niche that it masters. Parasites that manipulate hosts' behavior are often thought to represent resource-specialists based on a few spectacular examples of manipulation of the host's behavior. However, the determinants of which, and how many, hosts a manipulating parasite can exploit (i.e., niche breadth) are basically unknown. Here, I present an analysis based on published records of the use of hosts by 67 species from 38 genera of helminths inducing parasite increased trophic transmission, a widespread strategy of parasites that has been reported from many taxa of parasites and hosts. Using individual and multivariate analyses, I examined the effect of the host's and parasite's taxonomy, location of the parasite in the host, type of behavioral change, and the effect of debilitation on host-specificity, measured as the mean taxonomic relatedness of hosts that a parasite can manipulate. Host-specificity varied substantially across taxa suggesting great variation in the level of resource-specialization among manipulating parasites. Location of the parasite, level of debilitation, and type of host were all significant predictors of host-specificity. More specifically, hosts' behavioral modification that involves interaction with the central nervous system presumably restricts parasites to more closely related hosts than does manipulation of the host's behavior via debilitation of the host's physiology. The results of the analysis suggest that phylogenetic relatedness of hosts is a useful measure of host-specificity in comparative studies of the complexity of interactions taking place between manipulating parasites and their hosts. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Analysis of the Pantoea ananatis pan-genome reveals factors underlying its ability to colonize and interact with plant, insect and vertebrate hosts.

PubMed

De Maayer, Pieter; Chan, Wai Yin; Rubagotti, Enrico; Venter, Stephanus N; Toth, Ian K; Birch, Paul R J; Coutinho, Teresa A

2014-05-27

Pantoea ananatis is found in a wide range of natural environments, including water, soil, as part of the epi- and endophytic flora of various plant hosts, and in the insect gut. Some strains have proven effective as biological control agents and plant-growth promoters, while other strains have been implicated in diseases of a broad range of plant hosts and humans. By analysing the pan-genome of eight sequenced P. ananatis strains isolated from different sources we identified factors potentially underlying its ability to colonize and interact with hosts in both the plant and animal Kingdoms. The pan-genome of the eight compared P. ananatis strains consisted of a core genome comprised of 3,876 protein coding sequences (CDSs) and a sizeable accessory genome consisting of 1,690 CDSs. We estimate that ~106 unique CDSs would be added to the pan-genome with each additional P. ananatis genome sequenced in the future. The accessory fraction is derived mainly from integrated prophages and codes mostly for proteins of unknown function. Comparison of the translated CDSs on the P. ananatis pan-genome with the proteins encoded on all sequenced bacterial genomes currently available revealed that P. ananatis carries a number of CDSs with orthologs restricted to bacteria associated with distinct hosts, namely plant-, animal- and insect-associated bacteria. These CDSs encode proteins with putative roles in transport and metabolism of carbohydrate and amino acid substrates, adherence to host tissues, protection against plant and animal defense mechanisms and the biosynthesis of potential pathogenicity determinants including insecticidal peptides, phytotoxins and type VI secretion system effectors. P. ananatis has an 'open' pan-genome typical of bacterial species that colonize several different environments. The pan-genome incorporates a large number of genes encoding proteins that may enable P. ananatis to colonize, persist in and potentially cause disease symptoms in a wide range of plant and animal hosts.

A trans-Dominant Form of Gag Restricts Ty1 Retrotransposition and Mediates Copy Number Control

PubMed Central

Saha, Agniva; Mitchell, Jessica A.; Nishida, Yuri; Hildreth, Jonathan E.; Ariberre, Joshua A.; Gilbert, Wendy V.

2015-01-01

ABSTRACT Saccharomyces cerevisiae and Saccharomyces paradoxus lack the conserved RNA interference pathway and utilize a novel form of copy number control (CNC) to inhibit Ty1 retrotransposition. Although noncoding transcripts have been implicated in CNC, here we present evidence that a truncated form of the Gag capsid protein (p22) or its processed form (p18) is necessary and sufficient for CNC and likely encoded by Ty1 internal transcripts. Coexpression of p22/p18 and Ty1 decreases mobility more than 30,000-fold. p22/p18 cofractionates with Ty1 virus-like particles (VLPs) and affects VLP yield, protein composition, and morphology. Although p22/p18 and Gag colocalize in the cytoplasm, p22/p18 disrupts sites used for VLP assembly. Glutathione S-transferase (GST) affinity pulldowns also suggest that p18 and Gag interact. Therefore, this intrinsic Gag-like restriction factor confers CNC by interfering with VLP assembly and function and expands the strategies used to limit retroelement propagation. IMPORTANCE Retrotransposons dominate the chromosomal landscape in many eukaryotes, can cause mutations by insertion or genome rearrangement, and are evolutionarily related to retroviruses such as HIV. Thus, understanding factors that limit transposition and retroviral replication is fundamentally important. The present work describes a retrotransposon-encoded restriction protein derived from the capsid gene of the yeast Ty1 element that disrupts virus-like particle assembly in a dose-dependent manner. This form of copy number control acts as a molecular rheostat, allowing high levels of retrotransposition when few Ty1 elements are present and inhibiting transposition as copy number increases. Thus, yeast and Ty1 have coevolved a form of copy number control that is beneficial to both “host and parasite.” To our knowledge, this is the first Gag-like retrotransposon restriction factor described in the literature and expands the ways in which restriction proteins modulate retroelement replication. PMID:25609815

Specialist nectar-yeasts decline with urbanization in Berlin

NASA Astrophysics Data System (ADS)

Wehner, Jeannine; Mittelbach, Moritz; Rillig, Matthias C.; Verbruggen, Erik

2017-03-01

Nectar yeasts are common inhabitants of insect-pollinated flowers but factors determining their distribution are not well understood. We studied the influence of host identity, environmental factors related to pollution/urbanization, and the distance to a target beehive on local distribution of nectar yeasts within Robinia pseudoacacia L. and Tilia tomentosa Moench in Berlin, Germany. Nectar samples of six individuals per species were collected at seven sites in a 2 km radius from each target beehive and plated on YM-Agar to visualise the different morphotypes, which were then identified by sequencing a section of the 26S rDNA gene. Multivariate linear models were used to analyze the effects of all investigated factors on yeast occurrence per tree. Yeast distribution was mainly driven by host identity. The influence of the environmental factors (NO2, height of construction, soil sealing) strongly depended on the radius around the tree, similar to the distance of the sampled beehive. Incidence of specialist nectar-borne yeast species decreased with increasing pollution/urbanization index. Given that specialist yeast species gave way to generalist yeasts that have a reduced dependency on pollinators for between-flower dispersal, our results indicate that increased urbanization may restrict the movement of nectar-specialized yeasts, via limitations of pollinator foraging behavior.

Parasitism and venom of ectoparasitoid Scleroderma guani impairs host cellular immunity.

PubMed

Li, Li-Fang; Xu, Zhi-Wen; Liu, Nai-Yong; Wu, Guo-Xing; Ren, Xue-Min; Zhu, Jia-Ying

2018-06-01

Venom is a prominently maternal virulent factor utilized by parasitoids to overcome hosts immune defense. With respect to roles of this toxic mixture involved in manipulating hosts immunity, great interest has been mostly restricted to Ichneumonoidea parasitoids associated with polydnavirus (PDV), of which venom is usually considered as a helper component to enhance the role of PDV, and limited Chalcidoidea species. In contrast, little information is available in other parasitoids, especially ectoparasitic species not carrying PDV. The ectoparasitoid Scleroderma guani injects venom into its host, Tenebrio molitor, implying its venom was involved in suppression of hosts immune response for successful parasitism. Thus, we investigated the effects of parasitism and venom of this parasitoid on counteracting the cellular immunity of its host by examining changes of hemocyte counts, and hemocyte spreading and encapsulation ability. Total hemocyte counts were elevated in parasitized and venom-injected pupae. The spreading behavior of both granulocytes and plasmatocytes was impaired by parasitization and venom. High concentration of venom led to more severely increased hemocyte counts and suppression of hemocyte spreading. The ability of hemocyte encapsulation was inhibited by venom in vitro. In addition to immediate effects observed, venom showed persistent interference in hosts cellular immunity. These results indicate that venom alone from S. guani plays a pivotal role in blocking hosts cellular immune response, serving as a regulator that guarantees the successful development of its progenies. The findings provide a foundation for further investigation of the underlying mechanisms in immune inhibitory action of S. guani venom. © 2018 Wiley Periodicals, Inc.

Wolbachia Transfer from Rhagoletis cerasi to Drosophila simulans: Investigating the Outcomes of Host-Symbiont Coevolution

PubMed Central

Riegler, Markus; Charlat, Sylvain; Stauffer, Christian; Merçot, Hervé

2004-01-01

Wolbachia is an endosymbiont of diverse arthropod lineages that can induce various alterations of host reproduction for its own benefice. Cytoplasmic incompatibility (CI) is the most common phenomenon, which results in embryonic lethality when males that bear Wolbachia are mated with females that do not. In the cherry fruit fly, Rhagoletis cerasi, Wolbachia seems to be responsible for previously reported patterns of incompatibility between populations. Here we report on the artificial transfer of two Wolbachia variants (wCer1 and wCer2) from R. cerasi into Drosophila simulans, which was performed with two major goals in mind: first, to isolate wCer1 from wCer2 in order to individually test their respective abilities to induce CI in the new host; and, second, to test the theoretical prediction that recent Wolbachia-host associations should be characterized by high levels of CI, fitness costs to the new host, and inefficient transmission from mothers to offspring. wCer1 was unable to develop in the new host, resulting in its rapid loss after successful injection, while wCer2 was established in the new host. Transmission rates of wCer2 were low, and the infection showed negative fitness effects, consistent with our prediction, but CI levels were unexpectedly lower in the new host. Based on these parameter estimates, neither wCer1 nor wCer2 could be naturally maintained in D. simulans. The experiment thus suggests that natural Wolbachia transfer between species might be restricted by many factors, should the ecological barriers be bypassed. PMID:14711652

Wolbachia transfer from Rhagoletis cerasi to Drosophila simulans: investigating the outcomes of host-symbiont coevolution.

PubMed

Riegler, Markus; Charlat, Sylvain; Stauffer, Christian; Merçot, Hervé

2004-01-01

Wolbachia is an endosymbiont of diverse arthropod lineages that can induce various alterations of host reproduction for its own benefice. Cytoplasmic incompatibility (CI) is the most common phenomenon, which results in embryonic lethality when males that bear Wolbachia are mated with females that do not. In the cherry fruit fly, Rhagoletis cerasi, Wolbachia seems to be responsible for previously reported patterns of incompatibility between populations. Here we report on the artificial transfer of two Wolbachia variants (wCer1 and wCer2) from R. cerasi into Drosophila simulans, which was performed with two major goals in mind: first, to isolate wCer1 from wCer2 in order to individually test their respective abilities to induce CI in the new host; and, second, to test the theoretical prediction that recent Wolbachia-host associations should be characterized by high levels of CI, fitness costs to the new host, and inefficient transmission from mothers to offspring. wCer1 was unable to develop in the new host, resulting in its rapid loss after successful injection, while wCer2 was established in the new host. Transmission rates of wCer2 were low, and the infection showed negative fitness effects, consistent with our prediction, but CI levels were unexpectedly lower in the new host. Based on these parameter estimates, neither wCer1 nor wCer2 could be naturally maintained in D. simulans. The experiment thus suggests that natural Wolbachia transfer between species might be restricted by many factors, should the ecological barriers be bypassed.

Allelic variation in Salmonella: an underappreciated driver of adaptation and virulence

PubMed Central

Yue, Min; Schifferli, Dieter M.

2014-01-01

Salmonella enterica causes substantial morbidity and mortality in humans and animals. Infection and intestinal colonization by S. enterica require virulence factors that mediate bacterial binding and invasion of enterocytes and innate immune cells. Some S. enterica colonization factors and their alleles are host restricted, suggesting a potential role in regulation of host specificity. Recent data also suggest that colonization factors promote horizontal gene transfer of antimicrobial resistance genes by increasing the local density of Salmonella in colonized intestines. Although a profusion of genes are involved in Salmonella pathogenesis, the relative importance of their allelic variation has only been studied intensely in the type 1 fimbrial adhesin FimH. Although other Salmonella virulence factors demonstrate allelic variation, their association with specific metadata (e.g., host species, disease or carrier state, time and geographic place of isolation, antibiotic resistance profile, etc.) remains to be interrogated. To date, genome-wide association studies (GWAS) in bacteriology have been limited by the paucity of relevant metadata. In addition, due to the many variables amid metadata categories, a very large number of strains must be assessed to attain statistically significant results. However, targeted approaches in which genes of interest (e.g., virulence factors) are specifically sequenced alleviates the time-consuming and costly statistical GWAS analysis and increases statistical power, as larger numbers of strains can be screened for non-synonymous single nucleotide polymorphisms (SNPs) that are associated with available metadata. Congruence of specific allelic variants with specific metadata from strains that have a relevant clinical and epidemiological history will help to prioritize functional wet-lab and animal studies aimed at determining cause-effect relationships. Such an approach should be applicable to other pathogens that are being collected in well-curated repositories. PMID:24454310

Viruses infecting marine molluscs.

PubMed

Arzul, Isabelle; Corbeil, Serge; Morga, Benjamin; Renault, Tristan

2017-07-01

Although a wide range of viruses have been reported in marine molluscs, most of these reports rely on ultrastructural examination and few of these viruses have been fully characterized. The lack of marine mollusc cell lines restricts virus isolation capacities and subsequent characterization works. Our current knowledge is mostly restricted to viruses affecting farmed species such as oysters Crassostrea gigas, abalone Haliotis diversicolor supertexta or the scallop Chlamys farreri. Molecular approaches which are needed to identify virus affiliation have been carried out for a small number of viruses, most of them belonging to the Herpesviridae and birnaviridae families. These last years, the use of New Generation Sequencing approach has allowed increasing the number of sequenced viral genomes and has improved our capacity to investigate the diversity of viruses infecting marine molluscs. This new information has in turn allowed designing more efficient diagnostic tools. Moreover, the development of experimental infection protocols has answered some questions regarding the pathogenesis of these viruses and their interactions with their hosts. Control and management of viral diseases in molluscs mostly involve active surveillance, implementation of effective bio security measures and development of breeding programs. However factors triggering pathogen development and the life cycle and status of the viruses outside their mollusc hosts still need further investigations. Copyright © 2017 Elsevier Inc. All rights reserved.

Natural Variation in Resistance to Virus Infection in Dipteran Insects

PubMed Central

Palmer, William H.; Varghese, Finny S.

2018-01-01

The power and ease of Drosophila genetics and the medical relevance of mosquito-transmitted viruses have made dipterans important model organisms in antiviral immunology. Studies of virus–host interactions at the molecular and population levels have illuminated determinants of resistance to virus infection. Here, we review the sources and nature of variation in antiviral immunity and virus susceptibility in model dipteran insects, specifically the fruit fly Drosophila melanogaster and vector mosquitoes of the genera Aedes and Culex. We first discuss antiviral immune mechanisms and describe the virus-specificity of these responses. In the following sections, we review genetic and microbiota-dependent variation in antiviral immunity. In the final sections, we explore less well-studied sources of variation, including abiotic factors, sexual dimorphism, infection history, and endogenous viral elements. We borrow from work on other pathogen types and non-dipteran species when it parallels or complements studies in dipterans. Understanding natural variation in virus–host interactions may lead to the identification of novel restriction factors and immune mechanisms and shed light on the molecular determinants of vector competence. PMID:29522475

The Petunia GRAS Transcription Factor ATA/RAM1 Regulates Symbiotic Gene Expression and Fungal Morphogenesis in Arbuscular Mycorrhiza1

PubMed Central

Rich, Mélanie K.

2015-01-01

Arbuscular mycorrhiza (AM) is a mutual symbiosis that involves a complex symbiotic interface over which nutrients are exchanged between the plant host and the AM fungus. Dozens of genes in the host are required for the establishment and functioning of the interaction, among them nutrient transporters that mediate the uptake of mineral nutrients delivered by the fungal arbuscules. We have isolated in a genetic mutant screen a petunia (Petunia hybrida) GIBBERELLIC ACID INSENSITIVE, REPRESSOR of GIBBERELLIC ACID INSENSITIVE, and SCARECROW (GRAS)-type transcription factor, ATYPICAL ARBUSCULE (ATA), that acts as the central regulator of AM-related genes and is required for the morphogenesis of arbuscules. Forced mycorrhizal inoculations from neighboring wild-type plants revealed an additional role of ATA in restricting mycorrhizal colonization of the root meristem. The lack of ATA, which represents the ortholog of REQUIRED FOR ARBUSCULAR MYCORRHIZA1 in Medicago truncatula, renders the interaction completely ineffective, hence demonstrating the central role of AM-related genes for arbuscule development and function. PMID:25971550

The Petunia GRAS Transcription Factor ATA/RAM1 Regulates Symbiotic Gene Expression and Fungal Morphogenesis in Arbuscular Mycorrhiza.

PubMed

Rich, Mélanie K; Schorderet, Martine; Bapaume, Laure; Falquet, Laurent; Morel, Patrice; Vandenbussche, Michiel; Reinhardt, Didier

2015-07-01

Arbuscular mycorrhiza (AM) is a mutual symbiosis that involves a complex symbiotic interface over which nutrients are exchanged between the plant host and the AM fungus. Dozens of genes in the host are required for the establishment and functioning of the interaction, among them nutrient transporters that mediate the uptake of mineral nutrients delivered by the fungal arbuscules. We have isolated in a genetic mutant screen a petunia (Petunia hybrida) Gibberellic Acid Insensitive, Repressor of Gibberellic Acid Insensitive, and Scarecrow (GRAS)-type transcription factor, Atypical Arbuscule (ATA), that acts as the central regulator of AM-related genes and is required for the morphogenesis of arbuscules. Forced mycorrhizal inoculations from neighboring wild-type plants revealed an additional role of ATA in restricting mycorrhizal colonization of the root meristem. The lack of ATA, which represents the ortholog of Required For Arbuscular Mycorrhiza1 in Medicago truncatula, renders the interaction completely ineffective, hence demonstrating the central role of AM-related genes for arbuscule development and function. © 2015 American Society of Plant Biologists. All Rights Reserved.

A combination HIV reporter virus system for measuring post-entry event efficiency and viral outcome in primary CD4+ T cell subsets.

PubMed

Tilton, Carisa A; Tabler, Caroline O; Lucera, Mark B; Marek, Samantha L; Haqqani, Aiman A; Tilton, John C

2014-01-01

Fusion between the viral membrane of human immunodeficiency virus (HIV) and the host cell marks the end of the HIV entry process and the beginning of a series of post-entry events including uncoating, reverse transcription, integration, and viral gene expression. The efficiency of post-entry events can be modulated by cellular factors including viral restriction factors and can lead to several distinct outcomes: productive, latent, or abortive infection. Understanding host and viral proteins impacting post-entry event efficiency and viral outcome is critical for strategies to reduce HIV infectivity and to optimize transduction of HIV-based gene therapy vectors. Here, we report a combination reporter virus system measuring both membrane fusion and viral promoter-driven gene expression. This system enables precise determination of unstimulated primary CD4+ T cell subsets targeted by HIV, the efficiency of post-entry viral events, and viral outcome and is compatible with high-throughput screening and cell-sorting methods. Copyright © 2013 Elsevier B.V. All rights reserved.

Constitutively Expressed IFITM3 Protein in Human Endothelial Cells Poses an Early Infection Block to Human Influenza Viruses

PubMed Central

Sun, Xiangjie; Zeng, Hui; Kumar, Amrita; Belser, Jessica A.; Maines, Taronna R.

2016-01-01

ABSTRACT A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza viruses were capable of binding to host cellular receptors, becoming internalized and initiating hemifusion but failing to uncoat the viral nucleocapsid and to replicate in host nuclei. Unlike numerous cell types, including epithelial cells, we found that pulmonary endothelial cells constitutively express a high level of the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by small interfering RNA (siRNA) could partially rescue H1N1 virus infection in HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus infection in endothelial cells. In contrast, selected avian influenza viruses were able to escape IFITM3 restriction in endothelial cells, possibly by fusing in early endosomes at higher pH or by other, unknown mechanisms. Collectively, our study demonstrates that the human pulmonary endothelium possesses intrinsic immunity to human influenza viruses, in part due to the constitutive expression of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to escape this restriction, possibly contributing to virus-induced pneumonia and severe lung disease in humans. IMPORTANCE Avian influenza viruses, including H5N1 and H7N9, have been associated with severe respiratory disease and fatal outcomes in humans. Although acute respiratory distress syndrome (ARDS) and progressive pulmonary endothelial damage are known to be present during severe human infections, the role of pulmonary endothelial cells in the pathogenesis of avian influenza virus infections is largely unknown. By comparing human seasonal influenza strains to avian influenza viruses, we provide greater insight into the interaction of influenza virus with human pulmonary endothelial cells. We show that human influenza virus infection is blocked during the early stages of virus entry, which is likely due to the relatively high expression of the host antiviral factors IFITMs (interferon-induced transmembrane proteins) located in membrane-bound compartments inside cells. Overall, this study provides a mechanism by which human endothelial cells limit replication of human influenza virus strains, whereas avian influenza viruses overcome these restriction factors in this cell type. PMID:27707929

Constitutively Expressed IFITM3 Protein in Human Endothelial Cells Poses an Early Infection Block to Human Influenza Viruses.

PubMed

Sun, Xiangjie; Zeng, Hui; Kumar, Amrita; Belser, Jessica A; Maines, Taronna R; Tumpey, Terrence M

2016-12-15

A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza viruses were capable of binding to host cellular receptors, becoming internalized and initiating hemifusion but failing to uncoat the viral nucleocapsid and to replicate in host nuclei. Unlike numerous cell types, including epithelial cells, we found that pulmonary endothelial cells constitutively express a high level of the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by small interfering RNA (siRNA) could partially rescue H1N1 virus infection in HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus infection in endothelial cells. In contrast, selected avian influenza viruses were able to escape IFITM3 restriction in endothelial cells, possibly by fusing in early endosomes at higher pH or by other, unknown mechanisms. Collectively, our study demonstrates that the human pulmonary endothelium possesses intrinsic immunity to human influenza viruses, in part due to the constitutive expression of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to escape this restriction, possibly contributing to virus-induced pneumonia and severe lung disease in humans. Avian influenza viruses, including H5N1 and H7N9, have been associated with severe respiratory disease and fatal outcomes in humans. Although acute respiratory distress syndrome (ARDS) and progressive pulmonary endothelial damage are known to be present during severe human infections, the role of pulmonary endothelial cells in the pathogenesis of avian influenza virus infections is largely unknown. By comparing human seasonal influenza strains to avian influenza viruses, we provide greater insight into the interaction of influenza virus with human pulmonary endothelial cells. We show that human influenza virus infection is blocked during the early stages of virus entry, which is likely due to the relatively high expression of the host antiviral factors IFITMs (interferon-induced transmembrane proteins) located in membrane-bound compartments inside cells. Overall, this study provides a mechanism by which human endothelial cells limit replication of human influenza virus strains, whereas avian influenza viruses overcome these restriction factors in this cell type. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Ecological and genetic factors influencing the transition between host-use strategies in sympatric Heliconius butterflies.

PubMed

Merrill, R M; Naisbit, R E; Mallet, J; Jiggins, C D

2013-09-01

Shifts in host-plant use by phytophagous insects have played a central role in their diversification. Evolving host-use strategies will reflect a trade-off between selection pressures. The ecological niche of herbivorous insects is partitioned along several dimensions, and if populations remain in contact, recombination will break down associations between relevant loci. As such, genetic architecture can profoundly affect the coordinated divergence of traits and subsequently the ability to exploit novel habitats. The closely related species Heliconius cydno and H. melpomene differ in mimetic colour pattern, habitat and host-plant use. We investigate the selection pressures and genetic basis underlying host-use differences in these two species. Host-plant surveys reveal that H. melpomene specializes on a single species of Passiflora. This is also true for the majority of other Heliconius species in secondary growth forest at our study site, as expected under a model of interspecific competition. In contrast, H. cydno, which uses closed-forest habitats where both Heliconius and Passiflora are less common, appears not to be restricted by competition and uses a broad selection of the available Passiflora. However, other selection pressures are likely involved, and field experiments reveal that early larval survival of both butterfly species is highest on Passiflora menispermifolia, but most markedly so for H. melpomene, the specialist on that host. Finally, we demonstrate an association between host-plant acceptance and colour pattern amongst interspecific hybrids, suggesting that major loci underlying these important ecological traits are physically linked in the genome. Together, our results reveal ecological and genetic associations between shifts in habitat, host use and mimetic colour pattern that have likely facilitated both speciation and coexistence. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

48 CFR 252.236-7011 - Overseas architect-engineer services-Restriction to United States firms.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., resulting from this solicitation, to a United States firm or a joint venture of United States and host... firm or a joint venture of United States and host nation firms. (End of provision) [62 FR 2858, Jan. 17...

Pathogenesis of varicelloviruses in primates.

PubMed

Ouwendijk, Werner J D; Verjans, Georges M G M

2015-01-01

Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue, simian varicella virus (SVV). Both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. VZV is endemic worldwide and, although varicella is usually a benign disease in childhood, VZV reactivation is a significant cause of neurological disease in the elderly and in immunocompromised individuals. The pathogenesis of VZV infection remains ill-defined, mostly due to the species restriction of VZV that impedes studies in experimental animal models. SVV infection of non-human primates parallels virological, clinical, pathological and immunological features of human VZV infection, thereby providing an excellent model to study the pathogenesis of varicella and herpes zoster in its natural host. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import.

PubMed

Götz, Veronika; Magar, Linda; Dornfeld, Dominik; Giese, Sebastian; Pohlmann, Anne; Höper, Dirk; Kong, Byung-Whi; Jans, David A; Beer, Martin; Haller, Otto; Schwemmle, Martin

2016-03-18

To establish a new lineage in the human population, avian influenza A viruses (AIV) must overcome the intracellular restriction factor MxA. Partial escape from MxA restriction can be achieved when the viral nucleoprotein (NP) acquires the critical human-adaptive amino acid residues 100I/V, 283P, and 313Y. Here, we show that introduction of these three residues into the NP of an avian H5N1 virus renders it genetically unstable, resulting in viruses harboring additional single mutations, including G16D. These substitutions restored genetic stability yet again yielded viruses with varying degrees of attenuation in mammalian and avian cells. Additionally, most of the mutant viruses lost the capacity to escape MxA restriction, with the exception of the G16D virus. We show that MxA escape is linked to attenuation by demonstrating that the three substitutions promoting MxA escape disturbed intracellular trafficking of incoming viral ribonucleoprotein complexes (vRNPs), thereby resulting in impaired nuclear import, and that the additional acquired mutations only partially compensate for this import block. We conclude that for adaptation to the human host, AIV must not only overcome MxA restriction but also an associated block in nuclear vRNP import. This inherent difficulty may partially explain the frequent failure of AIV to become pandemic.

Host and viral determinants for MxB restriction of HIV-1 infection.

PubMed

Matreyek, Kenneth A; Wang, Weifeng; Serrao, Erik; Singh, Parmit Kumar; Levin, Henry L; Engelman, Alan

2014-10-25

Interferon-induced cellular proteins play important roles in the host response against viral infection. The Mx family of dynamin-like GTPases, which include MxA and MxB, target a wide variety of viruses. Despite considerable evidence demonstrating the breadth of antiviral activity of MxA, human MxB was only recently discovered to specifically inhibit lentiviruses. Here we assess both host and viral determinants that underlie MxB restriction of HIV-1 infection. Heterologous expression of MxB in human osteosarcoma cells potently inhibited HIV-1 infection (~12-fold), yet had little to no effect on divergent retroviruses. The anti-HIV effect manifested as a partial block in the formation of 2-long terminal repeat circle DNA and hence nuclear import, and we accordingly found evidence for an additional post-nuclear entry block. A large number of previously characterized capsid mutations, as well as mutations that abrogated integrase activity, counteracted MxB restriction. MxB expression suppressed integration into gene-enriched regions of chromosomes, similar to affects observed previously when cells were depleted for nuclear transport factors such as transportin 3. MxB activity did not require predicted GTPase active site residues or a series of unstructured loops within the stalk domain that confer functional oligomerization to related dynamin family proteins. In contrast, we observed an N-terminal stretch of residues in MxB to harbor key determinants. Protein localization conferred by a nuclear localization signal (NLS) within the N-terminal 25 residues, which was critical, was fully rescuable by a heterologous NLS. Consistent with this observation, a heterologous nuclear export sequence (NES) abolished full-length MxB activity. We additionally mapped sub-regions within amino acids 26-90 that contribute to MxB activity, finding sequences present within residues 27-50 particularly important. MxB inhibits HIV-1 by interfering with minimally two steps of infection, nuclear entry and post-nuclear trafficking and/or integration, without destabilizing the inherent catalytic activity of viral preintegration complexes. Putative MxB GTPase active site residues and stalk domain Loop 4 -- both previously shown to be necessary for MxA function -- were dispensable for MxB antiviral activity. Instead, we highlight subcellular localization and a yet-determined function(s) present in the unique MxB N-terminal region to be required for HIV-1 restriction.

A sulfur host based on titanium monoxide@carbon hollow spheres for advanced lithium–sulfur batteries

PubMed Central

Li, Zhen; Zhang, Jintao; Guan, Buyuan; Wang, Da; Liu, Li-Min; Lou, Xiong Wen (David)

2016-01-01

Lithium–sulfur batteries show advantages for next-generation electrical energy storage due to their high energy density and cost effectiveness. Enhancing the conductivity of the sulfur cathode and moderating the dissolution of lithium polysulfides are two key factors for the success of lithium–sulfur batteries. Here we report a sulfur host that overcomes both obstacles at once. With inherent metallic conductivity and strong adsorption capability for lithium-polysulfides, titanium monoxide@carbon hollow nanospheres can not only generate sufficient electrical contact to the insulating sulfur for high capacity, but also effectively confine lithium-polysulfides for prolonged cycle life. Additionally, the designed composite cathode further maximizes the lithium-polysulfide restriction capability by using the polar shells to prevent their outward diffusion, which avoids the need for chemically bonding all lithium-polysulfides on the surfaces of polar particles. PMID:27762261

Discovery of a proteinaceous cellular receptor for a norovirus

PubMed Central

Orchard, Robert C.; Wilen, Craig B.; Doench, John G.; Baldridge, Megan T.; McCune, Broc T.; Lee, Ying-Chiang J.; Lee, Sanghyun; Pruett-Miller, Shondra M.; Nelson, Christopher A.; Fremont, Daved H.; Virgin, Herbert W.

2017-01-01

Human noroviruses (NoV) are a leading cause of gastroenteritis globally, yet host factors required for NoV infection are poorly understood. We identified host molecules essential for murine NoV (MNoV) induced cell death including CD300lf as a proteinaceous receptor. CD300lf is essential for MNoV binding and replication in cell lines and primary cells. Additionally, Cd300lf−/− mice are resistant to MNoV infection. Expression of CD300lf in human cells breaks the species barrier restricting MNoV replication. The crystal structure of the CD300lf ectodomain revealed a potential ligand binding cleft composed of residues critical for MNoV infection. Therefore, the presence of a proteinaceous receptor is the primary determinant of MNoV species tropism while other components of cellular machinery required for NoV replication are conserved between humans and mice. PMID:27540007

Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus.

PubMed

Ebert, Gregor; Preston, Simon; Allison, Cody; Cooney, James; Toe, Jesse G; Stutz, Michael D; Ojaimi, Samar; Scott, Hamish W; Baschuk, Nikola; Nachbur, Ueli; Torresi, Joseph; Chin, Ruth; Colledge, Danielle; Li, Xin; Warner, Nadia; Revill, Peter; Bowden, Scott; Silke, John; Begley, C Glenn; Pellegrini, Marc

2015-05-05

Hepatitis B virus (HBV) infection can result in a spectrum of outcomes from immune-mediated control to disease progression, cirrhosis, and liver cancer. The host molecular pathways that influence and contribute to these outcomes need to be defined. Using an immunocompetent mouse model of chronic HBV infection, we identified some of the host cellular and molecular factors that impact on infection outcomes. Here, we show that cellular inhibitor of apoptosis proteins (cIAPs) attenuate TNF signaling during hepatitis B infection, and they restrict the death of infected hepatocytes, thus allowing viral persistence. Animals with a liver-specific cIAP1 and total cIAP2 deficiency efficiently control HBV infection compared with WT mice. This phenotype was partly recapitulated in mice that were deficient in cIAP2 alone. These results indicate that antagonizing the function of cIAPs may promote the clearance of HBV infection.

Human-specific bacterial pore-forming toxins induce programmed necrosis in erythrocytes.

PubMed

LaRocca, Timothy J; Stivison, Elizabeth A; Hod, Eldad A; Spitalnik, Steven L; Cowan, Peter J; Randis, Tara M; Ratner, Adam J

2014-08-26

A subgroup of the cholesterol-dependent cytolysin (CDC) family of pore-forming toxins (PFTs) has an unusually narrow host range due to a requirement for binding to human CD59 (hCD59), a glycosylphosphatidylinositol (GPI)-linked complement regulatory molecule. hCD59-specific CDCs are produced by several organisms that inhabit human mucosal surfaces and can act as pathogens, including Gardnerella vaginalis and Streptococcus intermedius. The consequences and potential selective advantages of such PFT host limitation have remained unknown. Here, we demonstrate that, in addition to species restriction, PFT ligation of hCD59 triggers a previously unrecognized pathway for programmed necrosis in primary erythrocytes (red blood cells [RBCs]) from humans and transgenic mice expressing hCD59. Because they lack nuclei and mitochondria, RBCs have typically been thought to possess limited capacity to undergo programmed cell death. RBC programmed necrosis shares key molecular factors with nucleated cell necroptosis, including dependence on Fas/FasL signaling and RIP1 phosphorylation, necrosome assembly, and restriction by caspase-8. Death due to programmed necrosis in RBCs is executed by acid sphingomyelinase-dependent ceramide formation, NADPH oxidase- and iron-dependent reactive oxygen species formation, and glycolytic formation of advanced glycation end products. Bacterial PFTs that are hCD59 independent do not induce RBC programmed necrosis. RBC programmed necrosis is biochemically distinct from eryptosis, the only other known programmed cell death pathway in mature RBCs. Importantly, RBC programmed necrosis enhances the growth of PFT-producing pathogens during exposure to primary RBCs, consistent with a role for such signaling in microbial growth and pathogenesis. In this work, we provide the first description of a new form of programmed cell death in erythrocytes (RBCs) that occurs as a consequence of cellular attack by human-specific bacterial toxins. By defining a new RBC death pathway that shares important components with necroptosis, a programmed necrosis module that occurs in nucleated cells, these findings expand our understanding of RBC biology and RBC-pathogen interactions. In addition, our work provides a link between cholesterol-dependent cytolysin (CDC) host restriction and promotion of bacterial growth in the presence of RBCs, which may provide a selective advantage to human-associated bacterial strains that elaborate such toxins and a potential explanation for the narrowing of host range observed in this toxin family. Copyright © 2014 LaRocca et al.

Nonclassical MHC Ib-restricted CD8+ T Cells Recognize Mycobacterium tuberculosis-Derived Protein Antigens and Contribute to Protection Against Infection

PubMed Central

Shang, Shaobin; Siddiqui, Sarah; Bian, Yao; Zhao, Jie; Wang, Chyung-Ru

2016-01-01

MHC Ib-restricted CD8+ T cells have been implicated in host defense against Mycobacterium tuberculosis (Mtb) infection. However, the relative contribution of various MHC Ib-restricted T cell populations to anti-mycobacterial immunity remains elusive. In this study, we used mice that lack MHC Ia (Kb-/-Db-/-), MHC Ia/H2-M3 (Kb-/-Db-/-M3-/-), or β2m (β2m-/-) to study the role of M3-restricted and other MHC Ib-restricted T cells in immunity against Mtb. Unlike their dominant role in Listeria infection, we found that M3-restricted CD8+ T cells only represented a small proportion of the CD8+ T cells responding to Mtb infection. Non-M3, MHC Ib-restricted CD8+ T cells expanded preferentially in the lungs of Mtb-infected Kb-/-Db-/-M3-/- mice, exhibited polyfunctional capacities and conferred protection against Mtb. These MHC Ib-restricted CD8+ T cells recognized several Mtb-derived protein antigens at a higher frequency than MHC Ia-restricted CD8+ T cells. The presentation of Mtb antigens to MHC Ib-restricted CD8+ T cells was mostly β2m-dependent but TAP-independent. Interestingly, a large proportion of Mtb-specific MHC Ib-restricted CD8+ T cells in Kb-/-Db-/-M3-/- mice were Qa-2-restricted while no considerable numbers of MR1 or CD1-restricted Mtb-specific CD8+ T cells were detected. Our findings indicate that nonclassical CD8+ T cells other than the known M3, CD1, and MR1-restricted CD8+ T cells contribute to host immune responses against Mtb infection. Targeting these MHC Ib-restricted CD8+ T cells would facilitate the design of better Mtb vaccines with broader coverage across MHC haplotypes due to the limited polymorphism of MHC class Ib molecules. PMID:27272249

Unexpected absence of genetic separation of a highly diverse population of hookworms from geographically isolated hosts.

PubMed

Haynes, Benjamin T; Marcus, Alan D; Higgins, Damien P; Gongora, Jaime; Gray, Rachael; Šlapeta, Jan

2014-12-01

The high natal site fidelity of endangered Australian sea lions (Neophoca cinerea) along the southern Australian coast suggests that their maternally transmitted parasitic species, such as hookworms, will have restricted potential for dispersal. If this is the case, we would expect to find a hookworm haplotype structure corresponding to that of the host mtDNA haplotype structure; that is, restricted among geographically separated colonies. In this study, we used a fragment of the cytochrome c oxidase I mitochondrial DNA (mtDNA) gene to investigate the diversity of hookworms (Uncinaria sanguinis) in N. cinerea to assess the importance of host distribution and ecology on the evolutionary history of the parasite. High haplotype (h=0.986) and nucleotide diversity (π=0.013) were seen, with 45 unique hookworm mtDNA haplotypes across N. cinerea colonies; with most of the variation (78%) arising from variability within hookworms from individual colonies. This is supported by the low genetic differentiation co-efficient (GST=0.007) and a high gene flow (Nm=35.25) indicating a high migration rate between the populations of hookworms. The haplotype network demonstrated no clear distribution and delineation of haplotypes according to geographical location. Our data rejects the vicariance hypothesis; that female host natal site fidelity and the transmammary route of infection restrict hookworm gene flow between N. cinerea populations and highlights the value of studies of parasite diversity and dispersal to challenge our understanding of parasite and host ecology. Copyright © 2014 Elsevier B.V. All rights reserved.

Genome specialization and decay of the strangles pathogen, Streptococcus equi, is driven by persistent infection

PubMed Central

Harris, Simon R.; Robinson, Carl; Steward, Karen F.; Webb, Katy S.; Paillot, Romain; Parkhill, Julian; Holden, Matthew T.G.; Waller, Andrew S.

2015-01-01

Strangles, the most frequently diagnosed infectious disease of horses worldwide, is caused by Streptococcus equi. Despite its prevalence, the global diversity and mechanisms underlying the evolution of S. equi as a host-restricted pathogen remain poorly understood. Here, we define the global population structure of this important pathogen and reveal a population replacement in the late 19th or early 20th Century. Our data reveal a dynamic genome that continues to mutate and decay, but also to amplify and acquire genes despite the organism having lost its natural competence and become host-restricted. The lifestyle of S. equi within the horse is defined by short-term acute disease, strangles, followed by long-term infection. Population analysis reveals evidence of convergent evolution in isolates from post-acute disease samples as a result of niche adaptation to persistent infection within a host. Mutations that lead to metabolic streamlining and the loss of virulence determinants are more frequently found in persistent isolates, suggesting that the pathogenic potential of S. equi reduces as a consequence of long-term residency within the horse post-acute disease. An example of this is the deletion of the equibactin siderophore locus that is associated with iron acquisition, which occurs exclusively in persistent isolates, and renders S. equi significantly less able to cause acute disease in the natural host. We identify several loci that may similarly be required for the full virulence of S. equi, directing future research toward the development of new vaccines against this host-restricted pathogen. PMID:26160165

A Systems Biology Approach Reveals that Tissue Tropism to West Nile Virus Is Regulated by Antiviral Genes and Innate Immune Cellular Processes

PubMed Central

Suthar, Mehul S.; Brassil, Margaret M.; Blahnik, Gabriele; McMillan, Aimee; Ramos, Hilario J.; Proll, Sean C.; Belisle, Sarah E.; Katze, Michael G.; Gale, Michael

2013-01-01

The actions of the RIG-I like receptor (RLR) and type I interferon (IFN) signaling pathways are essential for a protective innate immune response against the emerging flavivirus West Nile virus (WNV). In mice lacking RLR or IFN signaling pathways, WNV exhibits enhanced tissue tropism, indicating that specific host factors of innate immune defense restrict WNV infection and dissemination in peripheral tissues. However, the immune mechanisms by which the RLR and IFN pathways coordinate and function to impart restriction of WNV infection are not well defined. Using a systems biology approach, we defined the host innate immune response signature and actions that restrict WNV tissue tropism. Transcriptional profiling and pathway modeling to compare WNV-infected permissive (spleen) and nonpermissive (liver) tissues showed high enrichment for inflammatory responses, including pattern recognition receptors and IFN signaling pathways, that define restriction of WNV replication in the liver. Assessment of infected livers from Mavs−/−×Ifnar−/− mice revealed the loss of expression of several key components within the natural killer (NK) cell signaling pathway, including genes associated with NK cell activation, inflammatory cytokine production, and NK cell receptor signaling. In vivo analysis of hepatic immune cell infiltrates from WT mice demonstrated that WNV infection leads to an increase in NK cell numbers with enhanced proliferation, maturation, and effector action. In contrast, livers from Mavs−/−×Ifnar−/− infected mice displayed reduced immune cell infiltration, including a significant reduction in NK cell numbers. Analysis of cocultures of dendritic and NK cells revealed both cell-intrinsic and -extrinsic roles for the RLR and IFN signaling pathways to regulate NK cell effector activity. Taken together, these observations reveal a complex innate immune signaling network, regulated by the RLR and IFN signaling pathways, that drives tissue-specific antiviral effector gene expression and innate immune cellular processes that control tissue tropism to WNV infection. PMID:23544010

Effector-Triggered Immunity Determines Host Genotype-Specific Incompatibility in Legume-Rhizobium Symbiosis.

PubMed

Yasuda, Michiko; Miwa, Hiroki; Masuda, Sachiko; Takebayashi, Yumiko; Sakakibara, Hitoshi; Okazaki, Shin

2016-08-01

Symbiosis between legumes and rhizobia leads to the formation of N2-fixing root nodules. In soybean, several host genes, referred to as Rj genes, control nodulation. Soybean cultivars carrying the Rj4 gene restrict nodulation by specific rhizobia such as Bradyrhizobium elkanii We previously reported that the restriction of nodulation was caused by B. elkanii possessing a functional type III secretion system (T3SS), which is known for its delivery of virulence factors by pathogenic bacteria. In the present study, we investigated the molecular basis for the T3SS-dependent nodulation restriction in Rj4 soybean. Inoculation tests revealed that soybean cultivar BARC-2 (Rj4/Rj4) restricted nodulation by B. elkanii USDA61, whereas its nearly isogenic line BARC-3 (rj4/rj4) formed nitrogen-fixing nodules with the same strain. Root-hair curling and infection threads were not observed in the roots of BARC-2 inoculated with USDA61, indicating that Rj4 blocked B. elkanii infection in the early stages. Accumulation of H2O2 and salicylic acid (SA) was observed in the roots of BARC-2 inoculated with USDA61. Transcriptome analyses revealed that inoculation of USDA61, but not its T3SS mutant in BARC-2, induced defense-related genes, including those coding for hypersensitive-induced responsive protein, which act in effector-triggered immunity (ETI) in Arabidopsis. These findings suggest that B. elkanii T3SS triggers the SA-mediated ETI-type response in Rj4 soybean, which consequently blocks symbiotic interactions. This study revealed a common molecular mechanism underlying both plant-pathogen and plant-symbiont interactions, and suggests that establishment of a root nodule symbiosis requires the evasion or suppression of plant immune responses triggered by rhizobial effectors. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Methylotroph cloning vehicle

DOEpatents

Hanson, Richard S.; Allen, Larry N.

1989-04-25

A cloning vehicle comprising: a replication determinant effective for replicating the vehicle in a non-C.sub.1 -utilizing host and in a C.sub.1 -utilizing host; DNA effective to allow the vehicle to be mobilized from the non-C.sub.1 -utilizing host to the C.sub.1 -utilizing host; DNA providing resistance to two antibiotics to which the wild-type C.sub.1 -utilizing host is susceptible, each of the antibiotic resistance markers having a recognition site for a restriction endonuclease; a cos site; and a means for preventing replication in the C.sub.1 -utilizing host. The vehicle is used for complementation mapping as follows. DNA comprising a gene from the C.sub.1 -utilizing organism is inserted at the restriction nuclease recognition site, inactivating the antibiotic resistance marker at that site. The vehicle can then be used to form a cosmid structure to infect the non-C.sub.1 -utilizing (e.g., E. coli) host, and then conjugated with a selected C.sub.1 -utilizing mutant. Resistance to the other antibiotic by the mutant is a marker of the conjugation. Other phenotypical changes in the mutant, e.g., loss of an auxotrophic trait, is attributed to the C.sub.1 gene. The vector is also used to inactivate genes whose protein products catalyze side reactions that divert compounds from a biosynthetic pathway to a desired product, thereby producing an organism that makes the desired product in higher yields.

High-Throughput Dissection of AAV-Host Interactions: The Fast and the Curious.

PubMed

Herrmann, Anne-Kathrin; Grimm, Dirk

2018-05-18

Over fifty years after its initial description, Adeno-associated virus (AAV) remains a most exciting but also most elusive study object in basic or applied virology. On the one hand, its simple structure not only facilitates investigations into virus biology, but combined with the availability of numerous natural AAV variants with distinct infection efficiency and specificity also makes AAV a preferred substrate for engineering of gene delivery vectors. On the other hand, it is striking to witness a recent flurry of reports that highlight and partially close persistent gaps in our understanding of AAV virus and vector biology. This is all the more perplexing considering that recombinant AAVs have already been used in >160 clinical trials and recently been commercialized as gene therapeutics. Here, we discuss a reason for these advances in AAV research, namely, the advent and application of powerful high-throughput technology for dissection of AAV-host interactions and optimization of AAV gene therapy vectors. As relevant examples, we focus on the discovery of (i) a "new" cellular AAV receptor, AAVR, (ii) host restriction factors for AAV entry, and (iii) AAV capsid determinants that mediate trafficking through the blood-brain barrier. While (i)/(ii) are prototypes of extra- or intracellular AAV host factors that were identified via high-throughput screenings, (iii) exemplifies the power of molecular evolution to investigate the virus itself. In the future, we anticipate that these and other key technologies will continue to accelerate the dissection of AAV biology and will yield a wealth of new designer viruses for clinical use. Copyright © 2018. Published by Elsevier Ltd.

Molecular insights into Cassava brown streak virus susceptibility and resistance by profiling of the early host response.

PubMed

Anjanappa, Ravi B; Mehta, Devang; Okoniewski, Michal J; Szabelska-Berȩsewicz, Alicja; Gruissem, Wilhelm; Vanderschuren, Hervé

2018-02-01

Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV) are responsible for significant cassava yield losses in eastern sub-Saharan Africa. To study the possible mechanisms of plant resistance to CBSVs, we inoculated CBSV-susceptible and CBSV-resistant cassava varieties with a mixed infection of CBSVs using top-cleft grafting. Transcriptome profiling of the two cassava varieties was performed at the earliest time point of full infection (28 days after grafting) in the susceptible scions. The expression of genes encoding proteins in RNA silencing, salicylic acid pathways and callose deposition was altered in the susceptible cassava variety, but transcriptional changes were limited in the resistant variety. In total, the expression of 585 genes was altered in the resistant variety and 1292 in the susceptible variety. Transcriptional changes led to the activation of β-1,3-glucanase enzymatic activity and a reduction in callose deposition in the susceptible cassava variety. Time course analysis also showed that CBSV replication in susceptible cassava induced a strong up-regulation of RDR1, a gene previously reported to be a susceptibility factor in other potyvirus-host pathosystems. The differences in the transcriptional responses to CBSV infection indicated that susceptibility involves the restriction of callose deposition at plasmodesmata. Aniline blue staining of callose deposits also indicated that the resistant variety displays a moderate, but significant, increase in callose deposition at the plasmodesmata. Transcriptome data suggested that resistance does not involve typical antiviral defence responses (i.e. RNA silencing and salicylic acid). A meta-analysis of the current RNA-sequencing (RNA-seq) dataset and selected potyvirus-host and virus-cassava RNA-seq datasets revealed that the conservation of the host response across pathosystems is restricted to genes involved in developmental processes. © 2017 THE AUTHORS. MOLECULAR PLANT PATHOLOGY PUBLISHED BY BRITISH SOCIETY FOR PLANT PATHOLOGY AND JOHN WILEY & SONS LTD.

High nymphal host density and mortality negatively impact parasitoid complex during an insect herbivore outbreak.

PubMed

Hall, Aidan A G; Johnson, Scott N; Cook, James M; Riegler, Markus

2017-08-26

Insect herbivore outbreaks frequently occur and this may be due to factors that restrict top-down control by parasitoids, for example, host-parasitoid asynchrony, hyperparasitization, resource limitation and climate. Few studies have examined host-parasitoid density relationships during an insect herbivore outbreak in a natural ecosystem with diverse parasitoids. We studied parasitization patterns of Cardiaspina psyllids during an outbreak in a Eucalyptus woodland. First, we established the trophic roles of the parasitoids through a species-specific multiplex PCR approach on mummies from which parasitoids emerged. Then, we assessed host-parasitoid density relationships across three spatial scales (leaf, tree and site) over one year. We detected four endoparasitoid species of the family Encyrtidae (Hymenoptera); two primary parasitoid and one heteronomous hyperparasitoid Psyllaephagus species (the latter with female development as a primary parasitoid and male development as a hyperparasitoid), and the hyperparasitoid Coccidoctonus psyllae. Parasitoid development was host-synchronized, although synchrony between sites appeared constrained during winter (due to temperature differences). Parasitization was predominantly driven by one primary parasitoid species and was mostly inversely host-density dependent across the spatial scales. Hyperparasitization by C. psyllae was psyllid-density dependent at the site scale, however, this only impacted the rarer primary parasitoid. High larval parasitoid mortality due to density-dependent nymphal psyllid mortality (a consequence of resource limitation) compounded by a summer heat wave was incorporated in the assessment and resulted in density independence of host-parasitoid relationships. As such, high larval parasitoid mortality during insect herbivore outbreaks may contribute to the absence of host density-dependent parasitization during outbreak events. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Specialist Osmia bees forage indiscriminately among hybridizing Balsamorhiza floral hosts

Treesearch

James H. Cane

2011-01-01

Pollinators, even floral generalists (=polyleges), typically specialize during individual foraging bouts, infrequently switching between floral hosts. Such transient floral constancy restricts pollen flow, and thereby gene flow, to conspecific flowers in mixed plant communities. Where incipient flowering species meet, however, weak cross-fertility and often similar...

Host status of Meyer and Eureka lemons for Anastrepha A. ludens (Loew)

USDA-ARS?s Scientific Manuscript database

Host status for Mexican fruit fly Anastrepha ludens (Loew) was examined under laboratory conditions in cage infested Eureka and Meyer lemons. Our approach was to allow females to oviposit on the two cultivars in separate laboratory cages with aluminum foil covering to restrict the areas where femal...

Insights into Vibrio cholerae Intestinal Colonization from Monitoring Fluorescently Labeled Bacteria

PubMed Central

Millet, Yves A.; Alvarez, David; Ringgaard, Simon; von Andrian, Ulrich H.; Davis, Brigid M.; Waldor, Matthew K.

2014-01-01

Vibrio cholerae, the agent of cholera, is a motile non-invasive pathogen that colonizes the small intestine (SI). Most of our knowledge of the processes required for V. cholerae intestinal colonization is derived from enumeration of wt and mutant V. cholerae recovered from orogastrically infected infant mice. There is limited knowledge of the distribution of V. cholerae within the SI, particularly its localization along the villous axis, or of the bacterial and host factors that account for this distribution. Here, using confocal and intravital two-photon microscopy to monitor the localization of fluorescently tagged V. cholerae strains, we uncovered unexpected and previously unrecognized features of V. cholerae intestinal colonization. Direct visualization of the pathogen within the intestine revealed that the majority of V. cholerae microcolonies attached to the intestinal epithelium arise from single cells, and that there are notable regiospecific aspects to V. cholerae localization and factors required for colonization. In the proximal SI, V. cholerae reside exclusively within the developing intestinal crypts, but they are not restricted to the crypts in the more distal SI. Unexpectedly, V. cholerae motility proved to be a regiospecific colonization factor that is critical for colonization of the proximal, but not the distal, SI. Furthermore, neither motility nor chemotaxis were required for proper V. cholerae distribution along the villous axis or in crypts, suggesting that yet undefined processes enable the pathogen to find its niches outside the intestinal lumen. Finally, our observations suggest that host mucins are a key factor limiting V. cholerae intestinal colonization, particularly in the proximal SI where there appears to be a more abundant mucus layer. Collectively, our findings demonstrate the potent capacity of direct pathogen visualization during infection to deepen our understanding of host pathogen interactions. PMID:25275396

Novel Drosophila Viruses Encode Host-Specific Suppressors of RNAi

PubMed Central

van Mierlo, Joël T.; Overheul, Gijs J.; Obadia, Benjamin; van Cleef, Koen W. R.; Webster, Claire L.; Saleh, Maria-Carla; Obbard, Darren J.; van Rij, Ronald P.

2014-01-01

The ongoing conflict between viruses and their hosts can drive the co-evolution between host immune genes and viral suppressors of immunity. It has been suggested that an evolutionary ‘arms race’ may occur between rapidly evolving components of the antiviral RNAi pathway of Drosophila and viral genes that antagonize it. We have recently shown that viral protein 1 (VP1) of Drosophila melanogaster Nora virus (DmelNV) suppresses Argonaute-2 (AGO2)-mediated target RNA cleavage (slicer activity) to antagonize antiviral RNAi. Here we show that viral AGO2 antagonists of divergent Nora-like viruses can have host specific activities. We have identified novel Nora-like viruses in wild-caught populations of D. immigrans (DimmNV) and D. subobscura (DsubNV) that are 36% and 26% divergent from DmelNV at the amino acid level. We show that DimmNV and DsubNV VP1 are unable to suppress RNAi in D. melanogaster S2 cells, whereas DmelNV VP1 potently suppresses RNAi in this host species. Moreover, we show that the RNAi suppressor activity of DimmNV VP1 is restricted to its natural host species, D. immigrans. Specifically, we find that DimmNV VP1 interacts with D. immigrans AGO2, but not with D. melanogaster AGO2, and that it suppresses slicer activity in embryo lysates from D. immigrans, but not in lysates from D. melanogaster. This species-specific interaction is reflected in the ability of DimmNV VP1 to enhance RNA production by a recombinant Sindbis virus in a host-specific manner. Our results emphasize the importance of analyzing viral RNAi suppressor activity in the relevant host species. We suggest that rapid co-evolution between RNA viruses and their hosts may result in host species-specific activities of RNAi suppressor proteins, and therefore that viral RNAi suppressors could be host-specificity factors. PMID:25032815

Restriction Endonucleases from Invasive Neisseria gonorrhoeae Cause Double-Strand Breaks and Distort Mitosis in Epithelial Cells during Infection

PubMed Central

Weyler, Linda; Engelbrecht, Mattias; Mata Forsberg, Manuel; Brehwens, Karl; Vare, Daniel; Vielfort, Katarina; Wojcik, Andrzej; Aro, Helena

2014-01-01

The host epithelium is both a barrier against, and the target for microbial infections. Maintaining regulated cell growth ensures an intact protective layer towards microbial-induced cellular damage. Neisseria gonorrhoeae infections disrupt host cell cycle regulation machinery and the infection causes DNA double strand breaks that delay progression through the G2/M phase. We show that intracellular gonococci upregulate and release restriction endonucleases that enter the nucleus and damage human chromosomal DNA. Bacterial lysates containing restriction endonucleases were able to fragment genomic DNA as detected by PFGE. Lysates were also microinjected into the cytoplasm of cells in interphase and after 20 h, DNA double strand breaks were identified by 53BP1 staining. In addition, by using live-cell microscopy and NHS-ester stained live gonococci we visualized the subcellular location of the bacteria upon mitosis. Infected cells show dysregulation of the spindle assembly checkpoint proteins MAD1 and MAD2, impaired and prolonged M-phase, nuclear swelling, micronuclei formation and chromosomal instability. These data highlight basic molecular functions of how gonococcal infections affect host cell cycle regulation, cause DNA double strand breaks and predispose cellular malignancies. PMID:25460012

Restriction endonucleases from invasive Neisseria gonorrhoeae cause double-strand breaks and distort mitosis in epithelial cells during infection.

PubMed

Weyler, Linda; Engelbrecht, Mattias; Mata Forsberg, Manuel; Brehwens, Karl; Vare, Daniel; Vielfort, Katarina; Wojcik, Andrzej; Aro, Helena

2014-01-01

The host epithelium is both a barrier against, and the target for microbial infections. Maintaining regulated cell growth ensures an intact protective layer towards microbial-induced cellular damage. Neisseria gonorrhoeae infections disrupt host cell cycle regulation machinery and the infection causes DNA double strand breaks that delay progression through the G2/M phase. We show that intracellular gonococci upregulate and release restriction endonucleases that enter the nucleus and damage human chromosomal DNA. Bacterial lysates containing restriction endonucleases were able to fragment genomic DNA as detected by PFGE. Lysates were also microinjected into the cytoplasm of cells in interphase and after 20 h, DNA double strand breaks were identified by 53BP1 staining. In addition, by using live-cell microscopy and NHS-ester stained live gonococci we visualized the subcellular location of the bacteria upon mitosis. Infected cells show dysregulation of the spindle assembly checkpoint proteins MAD1 and MAD2, impaired and prolonged M-phase, nuclear swelling, micronuclei formation and chromosomal instability. These data highlight basic molecular functions of how gonococcal infections affect host cell cycle regulation, cause DNA double strand breaks and predispose cellular malignancies.

Host Specialization in the Charcoal Rot Fungus, Macrophomina phaseolina.

PubMed

Su, G; Suh, S O; Schneider, R W; Russin, J S

2001-02-01

ABSTRACT To investigate host specialization in Macrophomina phaseolina, the fungus was isolated from soybean, corn, sorghum, and cotton root tissue and soil from fields cropped continuously to these species for 15 years in St. Joseph, LA. Chlorate phenotype of each isolate was determined after growing on a minimal medium containing 120 mM potassium chlorate. Consistent differences in chlorate sensitivity were detected among isolates from different hosts and from soil versus root. To further explore genetic differentiation among fungal isolates from each host, these isolates were examined by restriction fragment length polymorphism and random amplified polymorphic DNA (RAPD) analysis. No variations were observed among isolates in restriction patterns of DNA fragments amplified by polymerase chain reaction covering the internal transcribed spacer region, 5.8S rRNA and part of 25S rRNA, suggesting that M. phaseolina constitutes a single species. Ten random primers were used to amplify the total DNA of 45 isolates, and banding patterns resulting from RAPD analysis were compared with the neighbor-joining method. Isolates from a given host were genetically similar to each other but distinctly different from those from other hosts. Chlorate-sensitive isolates were distinct from chlorate-resistant isolates within a given host. In greenhouse tests, soybean, sorghum, corn, and cotton were grown separately in soil infested with individual isolates of M. phaseolina that were chosen based on their host of origin and chlorate phenotype. Root colonization and plant weight were measured after harvesting. More colonization of corn roots occurred when corn was grown in soil containing corn isolates compared with isolates from other hosts. However, there was no host specialization in isolates from soybean, sorghum, or cotton. More root colonization in soybean occurred with chlorate-sensitive than with chlorate-resistant isolates.

Feline immunodeficiency virus cross-species transmission: Implications for emergence of new lentiviral infections

USGS Publications Warehouse

Lee, Justin; Malmberg, Jennifer L.; Wood, Britta A.; Hladky, Sahaja; Troyer, Ryan; Roelke, Melody; Cunningham, Mark W.; McBride, Roy; Vickers, Winston; Boyce, Walter; Boydston, Erin E.; Serieys, Laurel E.K.; Riley, Seth P D; Crooks, Kevin R.; VandeWoude, Sue

2016-01-01

Owing to a complex history of host-parasite coevolution, lentiviruses exhibit a high degree of species specificity. Given the well-documented viral archeology of HIV emergence following human exposures to SIV, understanding processes that promote successful cross-species lentiviral transmissions is highly relevant. We have previously reported natural cross-species transmission of a subtype of feline immunodeficiency virus, puma lentivirus A (PLVA), between bobcats (Lynx rufus) and mountain lions (Puma concolor) in a small number of animals in California and Florida. In this study we investigate host-specific selection pressures, within-host viral fitness, and inter- vs. intra-species transmission patterns among a larger collection of PLV isolates from free-ranging bobcats and mountain lions. Analysis of proviral and viral RNA levels demonstrates that PLVA fitness is severely restricted in mountain lions compared to bobcats. We document evidence of diversifying selection in three of six PLVA genomes from mountain lions, but did not detect selection among twenty PLVA isolates from bobcats. These findings support that PLVA is a bobcat-adapted virus, which is less fit in mountain lions and under intense selection pressure in the novel host. Ancestral reconstruction of transmission events reveals intraspecific PLVA transmission has occurred among panthers (Puma concolor coryi) in Florida following initial cross-species infection from bobcats. In contrast, interspecific transmission from bobcats to mountain lions predominates in California. These findings document outcomes of cross-species lentiviral transmission events among felids that compare to emergence of HIV from nonhuman primates.IMPORTANCE Cross-species transmission episodes can be singular, dead-end events or can result in viral replication and spread in the new species. The factors that determine which outcome will occur are complex, and the risk of new virus emergence is therefore difficult to predict. Here we use molecular techniques to evaluate transmission, fitness, and adaptation of puma lentivirus A (PLVA) between bobcats and mountain lions in two geographic regions. Our findings illustrate that mountain lion exposure to PLVA is relatively common, but does not routinely result in infections communicable in the new host. This is attributed to efficient species barriers that largely prevent lentiviral adaptation. However, the evolutionary capacity for lentiviruses to adapt to novel environments may ultimately overcome host restriction mechanisms over time and under certain ecological circumstances. This phenomenon provides a unique opportunity to examine cross-species transmission events leading to new lentiviral emergence.

Engineering super mycovirus donor strains of chestnut blight fungus by systematic disruption of multilocus vic genes.

PubMed

Zhang, Dong-Xiu; Nuss, Donald L

2016-02-23

Transmission of mycoviruses that attenuate virulence (hypovirulence) of pathogenic fungi is restricted by allorecognition systems operating in their fungal hosts. We report the use of systematic molecular gene disruption and classical genetics for engineering fungal hosts with superior virus transmission capabilities. Four of five diallelic virus-restricting allorecognition [vegetative incompatibility (vic)] loci were disrupted in the chestnut blight fungus Cryphonectria parasitica using an adapted Cre-loxP recombination system that allowed excision and recycling of selectable marker genes (SMGs). SMG-free, quadruple vic mutant strains representing both allelic backgrounds of the remaining vic locus were then produced through mating. In combination, these super donor strains were able to transmit hypoviruses to strains that were heteroallelic at one or all of the virus-restricting vic loci. These results demonstrate the feasibility of modulating allorecognition to engineer pathogenic fungi for more efficient transmission of virulence-attenuating mycoviruses and enhanced biological control potential.

IroT/mavN, a new iron-regulated gene involved in Legionella pneumophila virulence against amoebae and macrophages.

PubMed

Portier, Emilie; Zheng, Huaixin; Sahr, Tobias; Burnside, Denise M; Mallama, Celeste; Buchrieser, Carmen; Cianciotto, Nicholas P; Héchard, Yann

2015-04-01

Legionella pneumophila is a pathogenic bacterium commonly found in water. Eventually, it could be transmitted to humans via inhalation of contaminated aerosols. Iron is known as a key requirement for the growth of L. pneumophila in the environment and within its hosts. Many studies were performed to understand iron utilization by L. pneumophila but no global approaches were conducted. In this study, transcriptomic analyses were performed, comparing gene expression in L. pneumophila in standard versus iron restricted conditions. Among the regulated genes, a newly described one, lpp_2867, was highly induced in iron-restricted conditions. Mutants lacking this gene in L. pneumophila were not affected in siderophore synthesis or utilization. On the contrary, they were defective for growth on iron-depleted solid media and for ferrous iron uptake. A sequence analysis predicts that Lpp_2867 is a membrane protein, suggesting that it is involved in ferrous iron transport. We thus named it IroT, for iron transporter. Infection assays showed that the mutants are highly impaired in intracellular growth within their environmental host Acanthamoeba castellanii and human macrophages. Taken together, our results show that IroT is involved, directly or indirectly, in ferrous iron transport and is a key virulence factor for L. pneumophila. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

DDB1 Stimulates Viral Transcription of Hepatitis B Virus via HBx-Independent Mechanisms.

PubMed

Kim, Woohyun; Lee, Sooyoung; Son, Yeongnam; Ko, Chunkyu; Ryu, Wang-Shick

2016-11-01

HBx, a small regulatory protein of hepatitis B virus (HBV), augments viral DNA replication by stimulating viral transcription. Among numerous reported HBx-binding proteins, DDB1 has drawn attention, because DDB1 acts as a substrate receptor of the Cul4-DDB1 ubiquitin E3 ligase. Previous work reported that the DDB1-HBx interaction is indispensable for HBx-stimulated viral DNA replication, suggesting that the Cul4-DDB1 ubiquitin E3 ligase might target cellular restriction factors for ubiquitination and proteasomal degradation. To gain further insight into the DDB1-HBx interaction, we generated HBx mutants deficient for DDB1 binding (i.e., R96A, L98A, and G99A) and examined whether they support HBx-stimulated viral DNA replication. In contrast to data from previous reports, our results showed that the HBx mutants deficient for DDB1 binding supported viral DNA replication to nearly wild-type levels, revealing that the DDB1-HBx interaction is largely dispensable for HBx-stimulated viral DNA replication. Instead, we found that DDB1 directly stimulates viral transcription regardless of HBx expression. Through an HBV infection study, importantly, we demonstrated that DDB1 stimulates viral transcription from covalently closed circular DNA, a physiological template for viral transcription. Overall, we concluded that DDB1 stimulates viral transcription via a mechanism that does not involve an interaction with HBx. DDB1 constitutes a cullin-based ubiquitin E3 ligase, where DDB1 serves as an adaptor linking the cullin scaffold to the substrate receptor. Previous findings that the DDB1-binding ability of HBx is essential for HBx-stimulated viral DNA replication led to the hypothesis that HBx could downregulate host restriction factors that limit HBV replication through the cullin ubiquitin E3 ligase that requires the DDB1-HBx interaction. Consistent with this hypothesis, recent work identified Smc5/6 as a host restriction factor that is regulated by the viral cullin ubiquitin E3 ligase. In contrast, here we found that the DDB1-HBx interaction is largely dispensable for HBx-stimulated viral DNA replication. Instead, our results clearly showed that DDB1, regardless of HBx expression, enhances viral transcription. Overall, besides its role in the viral cullin ubiquitin E3 ligase, DDB1 itself stimulates viral transcription via HBx-independent mechanisms. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Gene Loss and Lineage-Specific Restriction-Modification Systems Associated with Niche Differentiation in the Campylobacter jejuni Sequence Type 403 Clonal Complex

PubMed Central

Morley, Laura; McNally, Alan; Paszkiewicz, Konrad; Corander, Jukka; Méric, Guillaume; Sheppard, Samuel K.; Blom, Jochen

2015-01-01

Campylobacter jejuni is a highly diverse species of bacteria commonly associated with infectious intestinal disease of humans and zoonotic carriage in poultry, cattle, pigs, and other animals. The species contains a large number of distinct clonal complexes that vary from host generalist lineages commonly found in poultry, livestock, and human disease cases to host-adapted specialized lineages primarily associated with livestock or poultry. Here, we present novel data on the ST403 clonal complex of C. jejuni, a lineage that has not been reported in avian hosts. Our data show that the lineage exhibits a distinctive pattern of intralineage recombination that is accompanied by the presence of lineage-specific restriction-modification systems. Furthermore, we show that the ST403 complex has undergone gene decay at a number of loci. Our data provide a putative link between the lack of association with avian hosts of C. jejuni ST403 and both gene gain and gene loss through nonsense mutations in coding sequences of genes, resulting in pseudogene formation. PMID:25795671

Prediction of Steps in the Evolution of Variola Virus Host Range

PubMed Central

Smithson, Chad; Purdy, Alex; Verster, Adrian J.; Upton, Chris

2014-01-01

Variola virus, the agent of smallpox, has a severely restricted host range (humans) but a devastatingly high mortality rate. Although smallpox has been eradicated by a World Health Organization vaccination program, knowledge of the evolutionary processes by which human super-pathogens such as variola virus arise is important. By analyzing the evolution of variola and other closely related poxviruses at the level of single nucleotide polymorphisms we detected a hotspot of genome variation within the smallpox ortholog of the vaccinia virus O1L gene, which is known to be necessary for efficient replication of vaccinia virus in human cells. These mutations in the variola virus ortholog and the subsequent loss of the functional gene from camelpox virus and taterapox virus, the two closest relatives of variola virus, strongly suggest that changes within this region of the genome may have played a key role in the switch to humans as a host for the ancestral virus and the subsequent host-range restriction that must have occurred to create the phenotype exhibited by smallpox. PMID:24626337

Prediction of steps in the evolution of variola virus host range.

PubMed

Smithson, Chad; Purdy, Alex; Verster, Adrian J; Upton, Chris

2014-01-01

Variola virus, the agent of smallpox, has a severely restricted host range (humans) but a devastatingly high mortality rate. Although smallpox has been eradicated by a World Health Organization vaccination program, knowledge of the evolutionary processes by which human super-pathogens such as variola virus arise is important. By analyzing the evolution of variola and other closely related poxviruses at the level of single nucleotide polymorphisms we detected a hotspot of genome variation within the smallpox ortholog of the vaccinia virus O1L gene, which is known to be necessary for efficient replication of vaccinia virus in human cells. These mutations in the variola virus ortholog and the subsequent loss of the functional gene from camelpox virus and taterapox virus, the two closest relatives of variola virus, strongly suggest that changes within this region of the genome may have played a key role in the switch to humans as a host for the ancestral virus and the subsequent host-range restriction that must have occurred to create the phenotype exhibited by smallpox.

Genetic Variability of Stolbur Phytoplasma in Hyalesthes obsoletus (Hemiptera: Cixiidae) and its Main Host Plants in Vineyard Agroecosystems.

PubMed

Landi, Lucia; Riolo, Paola; Murolo, Sergio; Romanazzi, Gianfranco; Nardi, Sandro; Isidoro, Nunzio

2015-08-01

Bois noir is an economically important grapevine yellows that is induced by 'Candidatus Phytoplasma solani' and principally vectored by the planthopper Hyalesthes obsoletus Signoret (Hemiptera: Cixiidae). This study explores the 'Ca. P. solani' genetic variability associated to the nettle-H. obsoletus and bindweed-H. obsoletus systems in vineyard agroecosystems of the central-eastern Italy. Molecular characterization of 'Ca. P. solani' isolates was carried out using polymerase chain reaction/restriction fragment length polymorphism to investigate the nonribosomal vmp1 gene. Seven phytoplasma vmp-types were detected among the host plants- and insect-associated field-collected samples. The vmp1 gene showed the highest polymorphism in the bindweed-H. obsoletus system, according to restriction fragment length polymorphism analysis, which is in agreement with nucleotide sequence analysis. Five vmp-types were associated with H. obsoletus from bindweed, of which one was solely restricted to planthoppers, with one genotype also in planthoppers from nettle. Type V12 was the most prevalent in both planthoppers and bindweed. H. obsoletus from nettle harbored three vmp-types, of which V3 was predominant. V3 was the only type detected for nettle. Our data demonstrate that planthoppers might have acquired some 'Ca. P. solani' profiles from other plant hosts before landing on nettle or bindweed. Overall, the different vmp1 gene rearrangements observed in these two plant hosts-H. obsoletus systems might represent different adaptations of the pathogen to the two host plants. Molecular information about the complex of vmp-types provides useful data for better understanding of Bois noir epidemiology in vineyard agroecosystem. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evidence of host-associated divergence from coral-eating snails (genus Coralliophila) in the Coral Triangle

NASA Astrophysics Data System (ADS)

Simmonds, Sara E.; Chou, Vincent; Cheng, Samantha H.; Rachmawati, Rita; Calumpong, Hilconida P.; Ngurah Mahardika, G.; Barber, Paul H.

2018-06-01

We studied how host-associations and geography shape the genetic structure of sister species of marine snails Coralliophila radula (A. Adams, 1853) and C. violacea (Kiener, 1836). These obligate ectoparasites prey upon corals and are sympatric throughout much of their ranges in coral reefs of the tropical and subtropical Indo-Pacific. We tested for population genetic structure of snails in relation to geography and their host corals using mtDNA (COI) sequences in minimum spanning trees and AMOVAs. We also examined the evolutionary relationships of their Porites host coral species using maximum likelihood trees of RAD-seq (restriction site-associated DNA sequencing) loci mapped to a reference transcriptome. A maximum likelihood tree of host corals revealed three distinct clades. Coralliophila radula showed a pronounced genetic break across the Sunda Shelf ( Φ CT = 0.735) but exhibited no genetic structure with respect to host. C. violacea exhibited significant geographic structure ( Φ CT = 0.427), with divergence among Hawaiian populations, the Coral Triangle and the Indian Ocean. Notably, C. violacea showed evidence of ecological divergence; two lineages were associated with different groups of host coral species, one widespread found at all sites, and the other restricted to the Coral Triangle. Sympatric populations of C. violacea found on different suites of coral species were highly divergent ( Φ CT = 0.561, d = 5.13%), suggesting that symbiotic relationships may contribute to lineage diversification in the Coral Triangle.

Methylotroph cloning vehicle

DOEpatents

Hanson, R.S.; Allen, L.N.

1989-04-25

A cloning vehicle comprising: a replication determinant effective for replicating the vehicle in a non-C[sub 1]-utilizing host and in a C[sub 1]-utilizing host; DNA effective to allow the vehicle to be mobilized from the non-C[sub 1]-utilizing host to the C[sub 1]-utilizing host; DNA providing resistance to two antibiotics to which the wild-type C[sub 1]-utilizing host is susceptible, each of the antibiotic resistance markers having a recognition site for a restriction endonuclease; a cos site; and a means for preventing replication in the C[sub 1]-utilizing host. The vehicle is used for complementation mapping as follows. DNA comprising a gene from the C[sub 1]-utilizing organism is inserted at the restriction nuclease recognition site, inactivating the antibiotic resistance marker at that site. The vehicle can then be used to form a cosmid structure to infect the non-C[sub 1]-utilizing (e.g., E. coli) host, and then conjugated with a selected C[sub 1]-utilizing mutant. Resistance to the other antibiotic by the mutant is a marker of the conjugation. Other phenotypical changes in the mutant, e.g., loss of an auxotrophic trait, is attributed to the C[sub 1] gene. The vector is also used to inactivate genes whose protein products catalyze side reactions that divert compounds from a biosynthetic pathway to a desired product, thereby producing an organism that makes the desired product in higher yields. 3 figs.

Gut Microbiota Dynamics during Dietary Shift in Eastern African Cichlid Fishes

PubMed Central

Baldo, Laura; Riera, Joan Lluís; Tooming-Klunderud, Ave; Albà, M. Mar; Salzburger, Walter

2015-01-01

The gut microbiota structure reflects both a host phylogenetic history and a signature of adaptation to the host ecological, mainly trophic niches. African cichlid fishes, with their array of closely related species that underwent a rapid dietary niche radiation, offer a particularly interesting system to explore the relative contribution of these two factors in nature. Here we surveyed the host intra- and interspecific natural variation of the gut microbiota of five cichlid species from the monophyletic tribe Perissodini of lake Tanganyika, whose members transitioned from being zooplanktivorous to feeding primarily on fish scales. The outgroup riverine species Astatotilapia burtoni, largely omnivorous, was also included in the study. Fusobacteria, Firmicutes and Proteobacteria represented the dominant components in the gut microbiota of all 30 specimens analysed according to two distinct 16S rRNA markers. All members of the Perissodini tribe showed a homogenous pattern of microbial alpha and beta diversities, with no significant qualitative differences, despite changes in diet. The recent diet shift between zooplantkon- and scale-eaters simply reflects on a significant enrichment of Clostridium taxa in scale-eaters where they might be involved in the scale metabolism. Comparison with the omnivorous species A. burtoni suggests that, with increased host phylogenetic distance and/or increasing herbivory, the gut microbiota begins differentiating also at qualitative level. The cichlids show presence of a large conserved core of taxa and a small set of core OTUs (average 13–15%), remarkably stable also in captivity, and putatively favoured by both restricted microbial transmission among related hosts (putatively enhanced by mouthbrooding behavior) and common host constraints. This study sets the basis for a future large-scale investigation of the gut microbiota of cichlids and its adaptation in the process of the host adaptive radiation. PMID:25978452

Host modulation therapeutics in periodontics: role as an adjunctive periodontal therapy.

PubMed

Shinwari, Muhammad Saad; Tanwir, Farzeen; Hyder, Pakiza Raza; Bin Saeed, Muhammad Humza

2014-09-01

Host Modulation Therapy (HMT) is a treatment concept that reduces tissue destruction and stabilizes or even regenerates inflammatory tissue by modifying host response factors. It has been used for treating osteoporosis and arthritis for several decades. However, its use in dentistry has only been recently reported. The objective of this article is to present a review of the various literatures available on HMT and also its role as adjunct therapy in periodontics. For identifying studies for this review, a PUBMED search was carried out in 2013 for all articles published till December 2012. The search was restricted to English language publications only. Longitudinal prospective and retrospective studies were included in the search. The key words used were: Host Modulation Therapy; Sub antimicrobial dose doxycycline and Non-Surgical Periodontal Therapy. The main outcomes sought were host modulation therapeutics in periodontics. Exclusion criteria included cross sectional studies, short case series as well as studies with short follow-up periods. There is a paucity of literature on HMT in periodontics although the only drug approved by United States Food and Drug Administration (FDA) is a subantimicrobial dose of doxycycline (SDD) with highly predictable results as a host modulating agent in periodontal diseases and also an effective adjunctive therapy in various diseases of periodontium. However, more randomized controlled trials are needed to obtain clinical guidelines on the usage of other host modulating agents as adjunct as well as definite therapy for periodontal diseases. SDD is an effective adjunct therapy when used in dosage of 20mg twice daily for minimum 3 months duration in various periodontal diseases with predictable clinical outcomes. It is also recommended that future clinical research on anti cytokine drugs, chemically modified tetracycline and other HMT agents should be conducted so that new drugs are available with highly predictable results.

Global genetic differentiation in a cosmopolitan pest of stored beans: effects of geography, host-plant usage and anthropogenic factors.

PubMed

Tuda, Midori; Kagoshima, Kumiko; Toquenaga, Yukihiko; Arnqvist, Göran

2014-01-01

Genetic differentiation can be promoted allopatrically by geographic isolation of populations due to limited dispersal ability and diversification over time or sympatrically through, for example, host-race formation. In crop pests, the trading of crops across the world can lead to intermixing of genetically distinct pest populations. However, our understanding of the importance of allopatric and sympatric genetic differentiation in the face of anthropogenic genetic intermixing is limited. Here, we examined global sequence variation in two mitochondrial and one nuclear genes in the seed beetle Callosobruchus maculatus that uses different legumes as hosts. We analyzed 180 samples from 42 populations of this stored bean pest from tropical and subtropical continents and archipelagos: Africa, the Middle East, South and Southeast Asia, Oceania and South America. For the mitochondrial genes, there was weak but significant genetic differentiation across continents/archipelagos. Further, we found pronounced differentiation among subregions within continents/archipelagos both globally and within Africa but not within Asia. We suggest that multiple introductions into Asia and subsequent intermixing within Asia have generated this pattern. The isolation by distance hypothesis was supported globally (with or without continents controlled) but not when host species was restricted to cowpeas Vigna unguiculata, the ancestral host of C. maculatus. We also document significant among-host differentiation both globally and within Asia, but not within Africa. We failed to reject a scenario of a constant population size in the recent past combined with selective neutrality for the mitochondrial genes. We conclude that mitochondrial DNA differentiation is primarily due to geographic isolation within Africa and to multiple invasions by different alleles, followed by host shifts, within Asia. The weak inter-continental differentiation is most likely due to frequent inter-continental gene flow mediated by human crop trade.

Genomic analysis of cold-active Colwelliaphage 9A and psychrophilic phage-host interactions.

PubMed

Colangelo-Lillis, Jesse R; Deming, Jody W

2013-01-01

The 104 kb genome of cold-active bacteriophage 9A, which replicates in the marine psychrophilic gamma-proteobacterium Colwellia psychrerythraea strain 34H (between -12 and 8 °C), was sequenced and analyzed to investigate elements of molecular adaptation to low temperature and phage-host interactions in the cold. Most characterized ORFs indicated closest similarity to gamma-proteobacteria and their phages, though no single module provided definitive phylogenetic grouping. A subset of primary structural features linked to psychrophily suggested that the majority of annotated phage proteins were not psychrophilic; those that were, primarily serve phage-specific functions and may also contribute to 9A's restricted temperature range for replication as compared to host. Comparative analyses suggest ribonucleotide reductase genes were acquired laterally from host. Neither restriction modification nor the CRISPR-Cas system appeared to be the predominant phage defense mechanism of Cp34H or other cold-adapted bacteria; we hypothesize that psychrophilic hosts rely more on the use of extracellular polymeric material to block cell surface receptors recognized by phages. The relative dearth of evidence for genome-specific defenses, genetic transfer events or auxiliary metabolic genes suggest that the 9A-Cp34H system may be less tightly coupled than are other genomically characterized marine phage-host systems, with possible implications for phage specificity under different environmental conditions.

Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments

PubMed Central

Verbruggen, Bas; Bickley, Lisa K.; van Aerle, Ronny; Bateman, Kelly S.; Stentiford, Grant D.; Santos, Eduarda M.; Tyler, Charles R.

2016-01-01

Since its emergence in the 1990s, White Spot Disease (WSD) has had major economic and societal impact in the crustacean aquaculture sector. Over the years shrimp farming alone has experienced billion dollar losses through WSD. The disease is caused by the White Spot Syndrome Virus (WSSV), a large dsDNA virus and the only member of the Nimaviridae family. Susceptibility to WSSV in a wide range of crustacean hosts makes it a major risk factor in the translocation of live animals and in commodity products. Currently there are no effective treatments for this disease. Understanding the molecular basis of disease processes has contributed significantly to the treatment of many human and animal pathogens, and with a similar aim considerable efforts have been directed towards understanding host–pathogen molecular interactions for WSD. Work on the molecular mechanisms of pathogenesis in aquatic crustaceans has been restricted by a lack of sequenced and annotated genomes for host species. Nevertheless, some of the key host–pathogen interactions have been established: between viral envelope proteins and host cell receptors at initiation of infection, involvement of various immune system pathways in response to WSSV, and the roles of various host and virus miRNAs in mitigation or progression of disease. Despite these advances, many fundamental knowledge gaps remain; for example, the roles of the majority of WSSV proteins are still unknown. In this review we assess current knowledge of how WSSV infects and replicates in its host, and critique strategies for WSD treatment. PMID:26797629

Enhanced production of enveloped viruses in BST-2-deficient cell lines.

PubMed

Yi, Eunbi; Oh, Jinsoo; Giao, Ngoc Q; Oh, Soohwan; Park, Se-Ho

2017-10-01

Despite all the advantages that cell-cultured influenza vaccines have over egg-based influenza vaccines, the inferior productivity of cell-culture systems is a major drawback that must be addressed. BST-2 (tetherin) is a host restriction factor which inhibits budding-out of various enveloped viruses from infected host cells. We developed BST-2-deficient MDCK and Vero cell lines to increase influenza virus release in cell culture. BST-2 gene knock-out resulted in increased release of viral particles into the culture medium, by at least 2-fold and up to 50-fold compared to release from wild-type counterpart cells depending on cell line and virus type. The effect was not influenza virus/MDCK/Vero-specific, but was also present in a broad range of host cells and virus families; we observed similar results in murine, human, canine, and monkey cell lines with viruses including MHV-68 (Herpesviridae), influenza A virus (Orthomyxoviridae), porcine epidemic diarrhea virus (Coronaviridae), and vaccinia virus (Poxviridae). Our results suggest that the elimination of BST-2 expression in virus-producing cell lines can enhance the production of viral vaccines. Biotechnol. Bioeng.2017;114: 2289-2297. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Ixodes scapularis saliva mitigates inflammatory cytokine secretion during Anaplasma phagocytophilum stimulation of immune cells

PubMed Central

2012-01-01

Background Ixodes scapularis saliva enables the transmission of infectious agents to the mammalian host due to its immunomodulatory, anesthetic and anti-coagulant properties. However, how I. scapularis saliva influences host cytokine secretion in the presence of the obligate intracellular rickettsial pathogen Anaplasma phagocytophilum remains elusive. Methods Bone marrow derived macrophages (BMDMs) were stimulated with pathogen associated molecular patterns (PAMPs) and A. phagocytophilum. Cytokine secretion was measured in the presence and absence of I. scapularis saliva. Human peripheral blood mononuclear cells (PBMCs) were also stimulated with Tumor Necrosis Factor (TNF)-α in the presence and absence of I. scapularis saliva and interleukin (IL)-8 was measured. Results I. scapularis saliva inhibits inflammatory cytokine secretion by macrophages during stimulation of Toll-like (TLR) and Nod-like receptor (NLR) signaling pathways. The effect of I. scapularis saliva on immune cells is not restricted to murine macrophages because decreasing levels of interleukin (IL)-8 were observed after TNF-α stimulation of human peripheral blood mononuclear cells. I. scapularis saliva also mitigates pro-inflammatory cytokine response by murine macrophages during challenge with A. phagocytophilum. Conclusions These findings suggest that I. scapularis may inhibit inflammatory cytokine secretion during rickettsial transmission at the vector-host interface. PMID:23050849

The welfare effects of restricting off-highway vehicle access to public lands

Treesearch

Paul M. Jakus; John E. Keith; Lu Liu; Dale Blahna

2010-01-01

Off-highway vehicle (OHV) use is a rapidly growing outdoor activity that results in a host of environmental and management problems. Federal agencies have been directed to develop travel management plans to improve recreation experiences, reduce social conflicts, and diminish environmental impacts of OHVs. We examine the effect of land access restrictions on the...

Cell-Specific IRF-3 Responses Protect against West Nile Virus Infection by Interferon-Dependent and -Independent Mechanisms

PubMed Central

Daffis, Stephane; Samuel, Melanie A; Keller, Brian C; Gale, Michael; Diamond, Michael S

2007-01-01

Interferon regulatory factor (IRF)-3 is a master transcription factor that activates host antiviral defense programs. Although cell culture studies suggest that IRF-3 promotes antiviral control by inducing interferon (IFN)-β, near normal levels of IFN-α and IFN-β were observed in IRF-3−/− mice after infection by several RNA and DNA viruses. Thus, the specific mechanisms by which IRF-3 modulates viral infection remain controversial. Some of this disparity could reflect direct IRF-3-dependent antiviral responses in specific cell types to control infection. To address this and determine how IRF-3 coordinates an antiviral response, we infected IRF-3−/− mice and two primary cells relevant for West Nile virus (WNV) pathogenesis, macrophages and cortical neurons. IRF-3−/− mice were uniformly vulnerable to infection and developed elevated WNV burdens in peripheral and central nervous system tissues, though peripheral IFN responses were largely normal. Whereas wild-type macrophages basally expressed key host defense molecules, including RIG-I, MDA5, ISG54, and ISG56, and restricted WNV infection, IRF-3−/− macrophages lacked basal expression of these host defense genes and supported increased WNV infection and IFN-α and IFN-β production. In contrast, wild-type cortical neurons were highly permissive to WNV and did not basally express RIG-I, MDA5, ISG54, and ISG56. IRF-3−/− neurons lacked induction of host defense genes and had blunted IFN-α and IFN-β production, yet exhibited only modestly increased viral titers. Collectively, our data suggest that cell-specific IRF-3 responses protect against WNV infection through both IFN-dependent and -independent programs. PMID:17676997

Effects of dietary antibiotic growth promoters on various aspects of host responses to Necrotic enteritis in broiler chickens

USDA-ARS?s Scientific Manuscript database

There is an increased interest in restricting the use of antibiotic growth promoters (AGPs) in animal agriculture. In order to better understand the mechanisms of AGPs in poultry, we carried out series of in vivo studies to investigate various aspects of host responses to AGPs in normal and necroti...

Host-Nation Operations: Soldier Training on Governance (HOST-G) Training Support Package

DTIC Science & Technology

2011-07-01

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Effects of DNA Extraction Procedures on Bacteroides Profiles in Fecal Samples From Various Animals Determined by Terminal Restriction Fragment Length Polymorphism Analysis

EPA Science Inventory

A major assumption in microbial source tracking is that some fecal bacteria are specific to a host animal, and thus provide unique microbial fingerprints that can be used to differentiate hosts. However, the DNA information obtained from a particular sample may be biased dependi...

Morphological variation and host range of two Ganoderma species from Papua New Guinea.

PubMed

Pilotti, Carmel A; Sanderson, Frank R; Aitken, Elizabeth A B; Armstrong, Wendy

2004-08-01

Two species of Ganoderma belonging to different subgenera which cause disease on oil palms in PNG are identified by basidiome morphology and the morphology of their basidiospores. The names G. boninense and G. tornatum have been applied. Significant pleiomorphy was observed in basidiome characters amongst the specimens examined. This variation in most instances did not correlate well with host or host status. Spore morphology appeared uniform within a species and spore indices varied only slightly. G. tornatum was found to have a broad host range whereas G. boninense appears to be restricted to palms in Papua New Guinea.

Dengue and Zika viruses subvert reticulophagy by NS2B3-mediated cleavage of FAM134B.

PubMed

Lennemann, Nicholas J; Coyne, Carolyn B

2017-02-01

The endoplasmic reticulum (ER) is exploited by several diverse viruses during their infectious life cycles. Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), utilize the ER as a source of membranes to establish their replication organelles and to facilitate their assembly and eventual maturation along the secretory pathway. To maintain normal homeostasis, host cells have evolved highly efficient processes to dynamically regulate the ER, such as through reticulophagy, a selective form of autophagy that leads to ER degradation. Here, we identify the ER-localized reticulophagy receptor FAM134B as a host cell restriction factor for both DENV and ZIKV. We show that RNAi-mediated depletion of FAM134B significantly enhances both DENV and ZIKV replication at an early stage of the viral life cycle. Consistent with its role as an antiviral host factor, we found that several flaviviruses including DENV, ZIKV, and West Nile virus (WNV), utilize their NS3 virally-encoded proteases to directly cleave FAM134B at a single site within its reticulon homology domain (RHD). Mechanistically, we show that NS3-mediated cleavage of FAM134B blocks the formation of ER and viral protein-enriched autophagosomes, suggesting that the cleavage of FAM134B serves to specifically suppress the reticulophagy pathway. These findings thus point to an important role for FAM134B and reticulophagy in the regulation of flavivirus infection and suggest that these viruses specifically target these pathways to promote viral replication.

Convergence and Divergence in the Evolution of the APOBEC3G-Vif Interaction Reveal Ancient Origins of Simian Immunodeficiency Viruses

PubMed Central

Compton, Alex A.; Emerman, Michael

2013-01-01

Naturally circulating lentiviruses are abundant in African primate species today, yet their origins and history of transmitting between hosts remain obscure. As a means to better understand the age of primate lentiviruses, we analyzed primate genomes for signatures of lentivirus-driven evolution. Specifically, we studied the adaptive evolution of host restriction factor APOBEC3G (A3G) in Old World Monkey (OWM) species. We find recurrent mutation of A3G in multiple primate lineages at sites that determine susceptibility to antagonism by the lentiviral accessory protein Vif. Using a broad panel of SIV Vif isolates, we demonstrate that natural variation in OWM A3G confers resistance to Vif-mediated degradation, suggesting that adaptive variants of the host factor were selected upon exposure to pathogenic lentiviruses at least 5–6 million years ago (MYA). Furthermore, in members of the divergent Colobinae subfamily of OWM, a multi-residue insertion event in A3G that arose at least 12 MYA blocks the activity of Vif, suggesting an even more ancient origin of SIV. Moreover, analysis of the lentiviruses associated with Colobinae monkeys reveal that the interface of the A3G-Vif interaction has shifted and given rise to a second genetic conflict. Our analysis of virus-driven evolution describes an ancient yet ongoing genetic conflict between simian primates and lentiviruses on a million-year time scale. PMID:23359341

Life in a rock pool: Radiation and population genetics of myxozoan parasites in hosts inhabiting restricted spaces.

PubMed

Bartošová-Sojková, Pavla; Lövy, Alena; Reed, Cecile C; Lisnerová, Martina; Tomková, Tereza; Holzer, Astrid S; Fiala, Ivan

2018-01-01

Intertidal rock pools where fish and invertebrates are in constant close contact due to limited space and water level fluctuations represent ideal conditions to promote life cycles in parasites using these two alternate hosts and to study speciation processes that could contribute to understanding the roles of parasitic species in such ecosystems. Gall bladder and liver samples from five clinid fish species (Blenniiformes: Clinidae) were morphologically and molecularly examined to determine the diversity, prevalence, distribution and host specificity of Ceratomyxa parasites (Cnidaria: Myxozoa) in intertidal habitats along the coast of South Africa. Phylogenetic relationships of clinid ceratomyxids based on the SSU rDNA, LSU rDNA and ITS regions were assessed additionally to the investigation of population genetic structure of Ceratomyxa cottoidii and subsequent comparison with the data known from type fish host Clinus cottoides. Seven Ceratomyxa species including previously described Ceratomyxa dehoopi and C. cottoidii were recognized in clinids. They represent a diverse group of rapidly evolving, closely related species with a remarkably high prevalence in their hosts, little host specificity and frequent concurrent infections, most probably as a result of parasite radiation after multiple speciation events triggered by limited host dispersal within restricted spaces. C. cottoidii represents the most common clinid parasite with a population structure characterized by young expanding populations in the south west and south east coast and by older populations in equilibrium on the west coast of its distribution. Parasite and fish host population structures show overlapping patterns and are very likely affected by similar oceanographic barriers possibly due to reduced host dispersal enhancing parasite community differentiation. While fish host specificity had little impact on parasite population structure, the habitat preference of the alternate invertebrate host as well as tidal water exchange may be additional crucial variables affecting the dispersal and associated population structure of C. cottoidii.

Life in a rock pool: Radiation and population genetics of myxozoan parasites in hosts inhabiting restricted spaces

PubMed Central

Reed, Cecile C.; Lisnerová, Martina; Tomková, Tereza; Holzer, Astrid S.; Fiala, Ivan

2018-01-01

Introduction Intertidal rock pools where fish and invertebrates are in constant close contact due to limited space and water level fluctuations represent ideal conditions to promote life cycles in parasites using these two alternate hosts and to study speciation processes that could contribute to understanding the roles of parasitic species in such ecosystems. Material and methods Gall bladder and liver samples from five clinid fish species (Blenniiformes: Clinidae) were morphologically and molecularly examined to determine the diversity, prevalence, distribution and host specificity of Ceratomyxa parasites (Cnidaria: Myxozoa) in intertidal habitats along the coast of South Africa. Phylogenetic relationships of clinid ceratomyxids based on the SSU rDNA, LSU rDNA and ITS regions were assessed additionally to the investigation of population genetic structure of Ceratomyxa cottoidii and subsequent comparison with the data known from type fish host Clinus cottoides. Results and discussion Seven Ceratomyxa species including previously described Ceratomyxa dehoopi and C. cottoidii were recognized in clinids. They represent a diverse group of rapidly evolving, closely related species with a remarkably high prevalence in their hosts, little host specificity and frequent concurrent infections, most probably as a result of parasite radiation after multiple speciation events triggered by limited host dispersal within restricted spaces. C. cottoidii represents the most common clinid parasite with a population structure characterized by young expanding populations in the south west and south east coast and by older populations in equilibrium on the west coast of its distribution. Parasite and fish host population structures show overlapping patterns and are very likely affected by similar oceanographic barriers possibly due to reduced host dispersal enhancing parasite community differentiation. While fish host specificity had little impact on parasite population structure, the habitat preference of the alternate invertebrate host as well as tidal water exchange may be additional crucial variables affecting the dispersal and associated population structure of C. cottoidii. PMID:29561884

T Cell Production of GM-CSF Protects the Host during Experimental Tuberculosis.

PubMed

Robinson, Richard T

2017-12-12

Although classically associated with myelopoiesis, granulocyte-macrophage colony-stimulating factor (GM-CSF) is increasingly recognized as being important for tuberculosis (TB) resistance. GM-CSF is expressed by nonhematopoietic and hematopoietic lineages following infection with Mycobacterium tuberculosis and is necessary to restrict M. tuberculosis growth in experimental models. Until the recent study by Rothchild et al. (mBio 8:e01514-17, 2017, https://doi.org/10.1128/mBio.01514-17), it was unknown whether GM-CSF-producing T cells contribute to TB resistance. Rothchild et al. identify which conventional and nonconventional T cell subsets produce GM-CSF during experimental TB, establish their protective nature using a variety of approaches, and provide a mechanistic basis for their ability to restrict M. tuberculosis growth. This commentary discusses the significance of these findings to basic and applied TB research. As translated to human disease, these findings suggest vaccine-mediated expansion of GM-CSF-producing T cells could be an effective prophylactic or therapeutic TB strategy. Copyright © 2017 Robinson.

Whole Genome Sequencing of Mycobacterium africanum Strains from Mali Provides Insights into the Mechanisms of Geographic Restriction

PubMed Central

Maiga, Mamoudou; Abeel, Thomas; Shea, Terrance; Desjardins, Christopher A.; Diarra, Bassirou; Baya, Bocar; Sanogo, Moumine; Diallo, Souleymane; Earl, Ashlee M.; Bishai, William R.

2016-01-01

Background Mycobacterium africanum, made up of lineages 5 and 6 within the Mycobacterium tuberculosis complex (MTC), causes up to half of all tuberculosis cases in West Africa, but is rarely found outside of this region. The reasons for this geographical restriction remain unknown. Possible reasons include a geographically restricted animal reservoir, a unique preference for hosts of West African ethnicity, and an inability to compete with other lineages outside of West Africa. These latter two hypotheses could be caused by loss of fitness or altered interactions with the host immune system. Methodology/Principal Findings We sequenced 92 MTC clinical isolates from Mali, including two lineage 5 and 24 lineage 6 strains. Our genome sequencing assembly, alignment, phylogeny and average nucleotide identity analyses enabled us to identify features that typify lineages 5 and 6 and made clear that these lineages do not constitute a distinct species within the MTC. We found that in Mali, lineage 6 and lineage 4 strains have similar levels of diversity and evolve drug resistance through similar mechanisms. In the process, we identified a putative novel streptomycin resistance mutation. In addition, we found evidence of person-to-person transmission of lineage 6 isolates and showed that lineage 6 is not enriched for mutations in virulence-associated genes. Conclusions This is the largest collection of lineage 5 and 6 whole genome sequences to date, and our assembly and alignment data provide valuable insights into what distinguishes these lineages from other MTC lineages. Lineages 5 and 6 do not appear to be geographically restricted due to an inability to transmit between West African hosts or to an elevated number of mutations in virulence-associated genes. However, lineage-specific mutations, such as mutations in cell wall structure, secretion systems and cofactor biosynthesis, provide alternative mechanisms that may lead to host specificity. PMID:26751217

Infection with Trypanosoma cruzi restricts the repertoire of parasite-specific CD8+ T cells leading to immunodominance.

PubMed

Tzelepis, Fanny; de Alencar, Bruna C G; Penido, Marcus L O; Claser, Carla; Machado, Alexandre V; Bruna-Romero, Oscar; Gazzinelli, Ricardo T; Rodrigues, Mauricio M

2008-02-01

Interference or competition between CD8(+) T cells restricted by distinct MHC-I molecules can be a powerful means to establish an immunodominant response. However, its importance during infections is still questionable. In this study, we describe that following infection of mice with the human pathogen Trypanosoma cruzi, an immunodominant CD8(+) T cell immune response is developed directed to an H-2K(b)-restricted epitope expressed by members of the trans-sialidase family of surface proteins. To determine whether this immunodominance was exerted over other non-H-2K(b)-restricted epitopes, we measured during infection of heterozygote mice, immune responses to three distinct epitopes, all expressed by members of the trans-sialidase family, recognized by H-2K(b)-, H-2K(k)-, or H-2K(d)-restricted CD8(+) T cells. Infected heterozygote or homozygote mice displayed comparably strong immune responses to the H-2K(b)-restricted immunodominant epitope. In contrast, H-2K(k)- or H-2K(d)-restricted immune responses were significantly impaired in heterozygote infected mice when compared with homozygote ones. This interference was not dependent on the dose of parasite or the timing of infection. Also, it was not seen in heterozygote mice immunized with recombinant adenoviruses expressing T. cruzi Ags. Finally, we observed that the immunodominance was circumvented by concomitant infection with two T. cruzi strains containing distinct immunodominant epitopes, suggesting that the operating mechanism most likely involves competition of T cells for limiting APCs. This type of interference never described during infection with a human parasite may represent a sophisticated strategy to restrict priming of CD8(+) T cells of distinct specificities, avoiding complete pathogen elimination by host effector cells, and thus favoring host parasitism.

Correlation of TBE Incidence with Red Deer and Roe Deer Abundance in Slovenia

PubMed Central

Knap, Nataša; Avšič-Županc, Tatjana

2013-01-01

Tick-borne encephalitis (TBE) is a virus infection which sometimes causes human disease. The TBE virus is found in ticks and certain vertebrate tick hosts in restricted endemic localities termed TBE foci. The formation of natural foci is a combination of several factors: the vectors, a suitable and numerous enough number of hosts and in a habitat with suitable vegetation and climate. The present study investigated the influence of deer on the incidence of tick-borne encephalitis. We were able to obtain data from deer culls. Using this data, the abundance of deer was estimated and temporal and spatial analysis was performed. The abundance of deer has increased in the past decades, as well as the incidence of tick-borne encephalitis. Temporal analysis confirmed a correlation between red deer abundance and tick-borne encephalitis occurrence. Additionally, spatial analysis established, that in areas with high incidence of tick-borne encephalitis red deer density is higher, compared to areas with no or few human cases of tick-borne encephalitis. However, such correlation could not be confirmed between roe deer density and the incidence of tick-borne encephalitis. This is presumably due to roe deer density being above a certain threshold so that availability of tick reproduction hosts has no apparent effect on ticks' host finding and consequently may not be possible to correlate with incidence of human TBE. PMID:23776668

Molecular interaction of Siglecs (sialic acid-binding Ig-like lectins) with sialylated ligands on Trypanosoma cruzi.

PubMed

Jacobs, Thomas; Erdmann, Hanna; Fleischer, Bernhard

2010-01-01

The protozoan parasite Trypanosoma cruzi (T. cruzi) is transmitted by blood-sucking insect vectors. After transmission, parasites circulate in the blood as trypomastigotes and invade a variety of cells to multiply intracellularly as amastigotes. The acute phase triggers an immune response that restricts the dissemination and proliferation of parasites. However, parasites are able to persist in different tissues for decades causing the pathology of Chagas' disease. T. cruzi expresses a trans-sialidase (TS). This unique enzyme transfers sialic acid from host glycoconjugates to mucin-like molecules on the parasite and is supposed to be a major virulence factor. TS and sialylated structures were implicated in the persistence of parasites. We discuss here the recent findings on the function of sialylated structures on the surface of T. cruzi with a special emphasis on their property to interact with sialic acid-binding Ig-like lectins, which may allow the parasite to modulate the immune system of the host. Copyright (c) 2009 Elsevier GmbH. All rights reserved.

Characterization of resistance to rhabdovirus and retrovirus infection in a human myeloid cell line.

PubMed

Boso, Guney; Somia, Nikunj V

2015-01-01

Viruses interact with various permissive and restrictive factors in host cells throughout their replication cycle. Cell lines that are non-permissive to viral infection have been particularly useful in discovering host cell proteins involved in viral life cycles. Here we describe the characterization of a human myeloid leukemia cell line, KG-1, that is resistant to infection by retroviruses and a Rhabdovirus. We show that KG-1 cells are resistant to infection by Vesicular Stomatits Virus as well as VSV Glycoprotein (VSVG) pseudotyped retroviruses due to a defect in binding. Moreover our results indicate that entry by xenotropic retroviral envelope glycoprotein RD114 is impaired in KG-1 cells. Finally we characterize a post- entry block in the early phase of the retroviral life cycle in KG-1 cells that renders the cell line refractory to infection. This cell line will have utility in discovering proteins involved in infection by VSV and HIV-1.

Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells

PubMed Central

Mahamed, Deeqa; Boulle, Mikael; Ganga, Yashica; Mc Arthur, Chanelle; Skroch, Steven; Oom, Lance; Catinas, Oana; Pillay, Kelly; Naicker, Myshnee; Rampersad, Sanisha; Mathonsi, Colisile; Hunter, Jessica; Wong, Emily B; Suleman, Moosa; Sreejit, Gopalkrishna; Pym, Alexander S; Lustig, Gila; Sigal, Alex

2017-01-01

A hallmark of pulmonary tuberculosis is the formation of macrophage-rich granulomas. These may restrict Mycobacterium tuberculosis (Mtb) growth, or progress to central necrosis and cavitation, facilitating pathogen growth. To determine factors leading to Mtb proliferation and host cell death, we used live cell imaging to track Mtb infection outcomes in individual primary human macrophages. Internalization of Mtb aggregates caused macrophage death, and phagocytosis of large aggregates was more cytotoxic than multiple small aggregates containing similar numbers of bacilli. Macrophage death did not result in clearance of Mtb. Rather, it led to accelerated intracellular Mtb growth regardless of prior activation or macrophage type. In contrast, bacillary replication was controlled in live phagocytes. Mtb grew as a clump in dead cells, and macrophages which internalized dead infected cells were very likely to die themselves, leading to a cell death cascade. This demonstrates how pathogen virulence can be achieved through numbers and aggregation states. DOI: http://dx.doi.org/10.7554/eLife.22028.001 PMID:28130921

Evolutionary Constraints Shaping Streptococcus pyogenes-Host Interactions.

PubMed

Wilkening, Reid V; Federle, Michael J

2017-07-01

Research on the Gram-positive human-restricted pathogen Streptococcus pyogenes (Group A Streptococcus, GAS) has long focused on invasive illness, the most severe manifestations of GAS infection. Recent advances in descriptions of molecular mechanisms of GAS virulence, coupled with massive sequencing efforts to isolate genomes, have allowed the field to better understand the molecular and evolutionary changes leading to pandemic strains. These findings suggest that it is necessary to rethink the dogma involving GAS pathogenesis, and that the most productive avenues for research going forward may be investigations into GAS in its 'normal' habitat, the nasopharynx, and its ability to either live with its host in an asymptomatic lifestyle or as an agent of superficial infections. This review will consider these advances, focusing on the natural history of GAS, the evolution of pandemic strains, and novel roles for several key virulence factors that may allow the field to better understand their physiological role. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Chemokine CXCL12 Is Essential for the Clearance of the Filaria Litomosoides sigmodontis in Resistant Mice

PubMed Central

Attout, Tarik; Ehrhardt, Katharina; Lhermitte-Vallarino, Nathaly; Hachet-Haas, Muriel; Galzi, Jean Luc; Brotin, Emilie; Bachelerie, Françoise; Gavotte, Laurent; Moulia, Catherine; Bain, Odile; Martin, Coralie

2012-01-01

Litomosoides sigmodontis is a cause of filarial infection in rodents. Once infective larvae overcome the skin barrier, they enter the lymphatic system and then settle in the pleural cavity, causing soft tissue infection. The outcome of infection depends on the parasite's modulatory ability and also on the immune response of the infected host, which is influenced by its genetic background. The goal of this study was to determine whether host factors such as the chemokine axis CXCL12/CXCR4, which notably participates in the control of immune surveillance, can influence the outcome of the infection. We therefore set up comparative analyses of subcutaneous infection by L. sigmodontis in two inbred mouse strains with different outcomes: one susceptible strain (BALB/c) and one resistant strain (C57BL/6). We showed that rapid parasite clearance was associated with a L. sigmodontis-specific CXCL12-dependent cell response in C57BL/6 mice. CXCL12 was produced mainly by pleural mesothelial cells during infection. Conversely, the delayed parasite clearance in BALB/c mice was neither associated with an increase in CXCL12 levels nor with cell influx into the pleural cavity. Remarkably, interfering with the CXCL12/CXCR4 axis in both strains of mice delayed filarial development, as evidenced by the postponement of the fourth molting process. Furthermore, the in vitro growth of stage 4 filariae was favored by the addition of low amounts of CXCL12. The CXCL12/CXCR4 axis thus appears to have a dual effect on the L. sigmodontis life cycle: by acting as a host-cell restriction factor for infection, and as a growth factor for worms. PMID:22511975

Genetic characterization, molecular epidemiology, and phylogenetic relationships of insect-specific viruses in the taxon Negevirus

PubMed Central

Nunes, Marcio R.T.; Contreras-Gutierrez, María Angélica; Guzman, Hilda; Martins, Livia C.; Barbirato, Mayla Feitoza; Savit, Chelsea; Balta, Victoria; Uribe, Sandra; Vivero, Rafael; Suaza, Juan David; Oliveira, Hamilton; Nunes Neto, Joaquin P.; Carvalho, Valeria L.; da Silva, Sandro Patroca; Cardoso, Jedson F.; de Oliveira, Rodrigo Santo; da Silva Lemos, Poliana; Wood, Thomas G.; Widen, Steven G.; Vasconcelos, Pedro F.C.; Fish, Durland; Vasilakis, Nikos; Tesh, Robert B.

2017-01-01

The recently described taxon Negevirus is comprised of a diverse group of insect-specific viruses isolated from mosquitoes and phlebotomine sandflies. In this study, a comprehensive genetic characterization, molecular, epidemiological and evolutionary analyses were conducted on nearly full-length sequences of 91 new negevirus isolates obtained in Brazil, Colombia, Peru, Panama, USA and Nepal. We demonstrated that these arthropod restricted viruses are clustered in two major phylogenetic groups with origins related to three plant virus genera (Cilevirus, Higrevirus and Blunevirus). Molecular analyses demonstrated that specific host correlations are not present with most negeviruses; instead, high genetic variability, wide host-range, and cross-species transmission were noted. The data presented here also revealed the existence of five novel insect-specific viruses falling into two arthropod-restrictive virus taxa, previously proposed as distinct genera, designated Nelorpivirus and Sandewavirus. Our results provide a better understanding of the molecular epidemiology, evolution, taxonomy and stability of this group of insect-restricted viruses. PMID:28193550

Genetic characterization, molecular epidemiology, and phylogenetic relationships of insect-specific viruses in the taxon Negevirus.

PubMed

Nunes, Marcio R T; Contreras-Gutierrez, María Angélica; Guzman, Hilda; Martins, Livia C; Barbirato, Mayla Feitoza; Savit, Chelsea; Balta, Victoria; Uribe, Sandra; Vivero, Rafael; Suaza, Juan David; Oliveira, Hamilton; Nunes Neto, Joaquin P; Carvalho, Valeria L; da Silva, Sandro Patroca; Cardoso, Jedson F; de Oliveira, Rodrigo Santo; da Silva Lemos, Poliana; Wood, Thomas G; Widen, Steven G; Vasconcelos, Pedro F C; Fish, Durland; Vasilakis, Nikos; Tesh, Robert B

2017-04-01

The recently described taxon Negevirus is comprised of a diverse group of insect-specific viruses isolated from mosquitoes and phlebotomine sandflies. In this study, a comprehensive genetic characterization, molecular, epidemiological and evolutionary analyses were conducted on nearly full-length sequences of 91 new negevirus isolates obtained in Brazil, Colombia, Peru, Panama, USA and Nepal. We demonstrated that these arthropod restricted viruses are clustered in two major phylogenetic groups with origins related to three plant virus genera (Cilevirus, Higrevirus and Blunevirus). Molecular analyses demonstrated that specific host correlations are not present with most negeviruses; instead, high genetic variability, wide host-range, and cross-species transmission were noted. The data presented here also revealed the existence of five novel insect-specific viruses falling into two arthropod-restrictive virus taxa, previously proposed as distinct genera, designated Nelorpivirus and Sandewavirus. Our results provide a better understanding of the molecular epidemiology, evolution, taxonomy and stability of this group of insect-restricted viruses. Copyright © 2017 Elsevier Inc. All rights reserved.

PARP1 restricts Epstein Barr Virus lytic reactivation by binding the BZLF1 promoter.

PubMed

Lupey-Green, Lena N; Moquin, Stephanie A; Martin, Kayla A; McDevitt, Shane M; Hulse, Michael; Caruso, Lisa B; Pomerantz, Richard T; Miranda, Jj L; Tempera, Italo

2017-07-01

The Epstein Barr virus (EBV) genome persists in infected host cells as a chromatinized episome and is subject to chromatin-mediated regulation. Binding of the host insulator protein CTCF to the EBV genome has an established role in maintaining viral latency type, and in other herpesviruses, loss of CTCF binding at specific regions correlates with viral reactivation. Here, we demonstrate that binding of PARP1, an important cofactor of CTCF, at the BZLF1 lytic switch promoter restricts EBV reactivation. Knockdown of PARP1 in the Akata-EBV cell line significantly increases viral copy number and lytic protein expression. Interestingly, CTCF knockdown has no effect on viral reactivation, and CTCF binding across the EBV genome is largely unchanged following reactivation. Moreover, EBV reactivation attenuates PARP activity, and Zta expression alone is sufficient to decrease PARP activity. Here we demonstrate a restrictive function of PARP1 in EBV lytic reactivation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Food restriction followed by refeeding with a casein- or whey-based diet differentially affects the gut microbiota of pre-pubertal male rats.

PubMed

Masarwi, Majdi; Solnik, Hadas Isaac; Phillip, Moshe; Yaron, Sima; Shamir, Raanan; Pasmanic-Chor, Metsada; Gat-Yablonski, Galia

2018-01-01

Researchers are gaining an increasing understanding of host-gut microbiota interactions, but studies of the role of gut microbiota in linear growth are scarce. The aim of this study was to investigate the effect of food restriction and refeeding with different diets on gut microbiota composition in fast-growing rats. Young male Sprague-Dawley rats were fed regular rat chow ad libitum (control group) or subjected to 40% food restriction for 36 days followed by continued restriction or ad libitum refeeding for 24 days. Three different diets were used for refeeding: regular vegetarian protein chow or chow in which the sole source of protein was casein or whey. In the control group, the composition of the microbiota remained stable. Food restriction for 60 days led to a significant change in the gut microbiota at the phylum level, with a reduction in the abundance of Firmicutes and an increase in Bacteroidetes and Proteobacteria. Rats refed with the vegetarian protein diet had a different microbiota composition than rats refed the casein- or whey-based diet. Similarities in the bacterial population were found between rats refed vegetarian protein or a whey-based diet and control rats, and between rats refed a casein-based diet and rats on continued restriction. There was a significant strong correlation between the gut microbiota and growth parameters: humerus length, epiphyseal growth plate height, and levels of insulin-like growth factor 1 and leptin. In conclusion, the type of protein in the diet significantly affects the gut microbiota and, thereby, may affect animal's health. Copyright © 2017 Elsevier Inc. All rights reserved.

GENETIC CONTROL OF RESTRICTION AND MODIFICATION IN ESCHERICHIA COLI1

PubMed Central

Boyer, Herbert

1964-01-01

Boyer, Herbert (Yale University, New Haven, Conn.). Genetic control of restriction and modification in Escherichia coli. J. Bacteriol. 88:1652–1660. 1964.—Bacterial crosses with K-12 strains of Escherichia coli as Hfr donors (Hfr Hayes, Hfr Cavalli, and Hfr P4X-6) and B/r strains of E. coli as F− recipients were found to differ from crosses between K-12 Hfr donors and K-12 F− recipients in two ways: (i) recombinants (leu, pro, lac, and gal) did not appear at discrete time intervals but did appear simultaneously 30 min after matings were initiated, and (ii) the linkage of unselected markers to selected markers was reduced. Integration of a genetic region linked to the threonine locus of K-12 into the B/r genome resulted in a hybrid which no longer gave anomalous results in conjugation experiments. A similar region of the B strain was introduced into the K-12 strain, which then behaved as a typical B F− recipient. These observations are interpreted as the manifestation of host-controlled modification and restriction on the E. coli chromosome. This was verified by experiments on the restriction and modification of the bacteriophage lambda, F-lac, F-gal, and sex-factor, F1. It was found that the genetic region that controlled the mating responses of the K-12 and B/r strains also controlled the modification and restriction properties of these two strains. The genes responsible for the restricting and modifying properties of the K-12 and B strains of E. coli were found to be allelic, linked to each other, and linked to the threonine locus. PMID:14240953

Herbivores limit the population size of big-leaf mahogany trees in an Amazonian forest

Treesearch

Julian M. Norghauer; Christopher M. Free; R. Matthew Landis; James Grogan; Jay R. Malcolm; Sean C. Thomas

2015-01-01

The Janzen -- Connell hypothesis proposes that specialized herbivores maintain high numbers of tree species in tropical forests by restricting adult recruitment so that host populations remain at low densities. We tested this prediction for the large timber tree species, Swietenia macrophylla, whose seeds and seedlings are preyed upon by small mammals and a host-...

Global Screening of Antiviral Genes that Suppress Baculovirus Transgene Expression in Mammalian Cells.

PubMed

Wang, Chia-Hung; Naik, Nenavath Gopal; Liao, Lin-Li; Wei, Sung-Chan; Chao, Yu-Chan

2017-09-15

Although baculovirus has been used as a safe and convenient gene delivery vector in mammalian cells, baculovirus-mediated transgene expression is less effective in various mammalian cell lines. Identification of the negative regulators in host cells is necessary to improve baculovirus-based expression systems. Here, we performed high-throughput shRNA library screening, targeting 176 antiviral innate immune genes, and identified 43 host restriction factor genes in a human A549 lung carcinoma cell line. Among them, suppression of receptor interaction protein kinase 1 (RIP1, also known as RIPK1) significantly increased baculoviral transgene expression without resulting in significant cell death. Silencing of RIP1 did not affect viral entry or cell viability, but it did inhibit nuclear translocation of the IRF3 and NF-κB transcription factors. Also, activation of downstream signaling mediators (such as TBK1 and IRF7) was affected, and subsequent interferon and cytokine gene expression levels were abolished. Further, Necrostatin-1 (Nec-1)-an inhibitor of RIP1 kinase activity-dramatically increased baculoviral transgene expression in RIP1-silenced cells. Using baculovirus as a model system, this study presents an initial investigation of large numbers of human cell antiviral innate immune response factors against a "nonadaptive virus." In addition, our study has made baculovirus a more efficient gene transfer vector for some of the most frequently used mammalian cell systems.

Simvastatin inhibits Staphylococcus aureus host cell invasion through modulation of isoprenoid intermediates

PubMed Central

Horn, Mary P.; Knecht, Sharmon M.; Rushing, Frances L.; Birdsong, Julie; Siddall, C. Parker; Johnson, Charron M.; Abraham, Terri N.; Brown, Amy; Volk, Catherine B.; Gammon, Kelly; Bishop, Derron L.; McKillip, John L.; McDowell, Susan A.

2015-01-01

Patients on a statin regimen are at a decreased risk of death due to bacterial sepsis. We have found that protection by simvastatin includes the inhibition of host cell invasion by Staphylococcus aureus, the most common etiologic agent of sepsis. Inhibition was due in part to depletion of isoprenoid intermediates within the cholesterol biosynthesis pathway and led to the cytosolic accumulation of the small-guanosine triphosphatases (GTPases) CDC42, Rac, and RhoB. Actin stress fiber disassembly required for host invasion was attenuated by simvastatin and by the inhibition of phosphoinositide 3-kinase (PI3K) activity. PI3K relies on coupling to prenylated proteins, such as this subset of small-GTPases, for access to membrane-bound phosphoinositide to mediate stress fiber disassembly. Therefore, we examined whether simvastatin restricts PI3K cellular localization. In response to simvastatin, the PI3K isoform p85, coupled to these small-GTPases, was sequestered within the cytosol. From these findings, we propose a mechanism whereby simvastatin restricts p85 localization, inhibiting actin dynamics required for bacterial endocytosis. This may provide the basis for protection at the level of the host in invasive infections by S. aureus. PMID:18388257

Human and Murine IFIT1 Proteins Do Not Restrict Infection of Negative-Sense RNA Viruses of the Orthomyxoviridae, Bunyaviridae, and Filoviridae Families.

PubMed

Pinto, Amelia K; Williams, Graham D; Szretter, Kristy J; White, James P; Proença-Módena, José Luiz; Liu, Gai; Olejnik, Judith; Brien, James D; Ebihara, Hideki; Mühlberger, Elke; Amarasinghe, Gaya; Diamond, Michael S; Boon, Adrianus C M

2015-09-01

Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) is a host protein with reported cell-intrinsic antiviral activity against several RNA viruses. The proposed basis for the activity against negative-sense RNA viruses is the binding to exposed 5'-triphosphates (5'-ppp) on the genome of viral RNA. However, recent studies reported relatively low binding affinities of IFIT1 for 5'-ppp RNA, suggesting that IFIT1 may not interact efficiently with this moiety under physiological conditions. To evaluate the ability of IFIT1 to have an impact on negative-sense RNA viruses, we infected Ifit1(-/-) and wild-type control mice and primary cells with four negative-sense RNA viruses (influenza A virus [IAV], La Crosse virus [LACV], Oropouche virus [OROV], and Ebola virus) corresponding to three distinct families. Unexpectedly, a lack of Ifit1 gene expression did not result in increased infection by any of these viruses in cell culture. Analogously, morbidity, mortality, and viral burdens in tissues were identical between Ifit1(-/-) and control mice after infection with IAV, LACV, or OROV. Finally, deletion of the human IFIT1 protein in A549 cells did not affect IAV replication or infection, and reciprocally, ectopic expression of IFIT1 in HEK293T cells did not inhibit IAV infection. To explain the lack of antiviral activity against IAV, we measured the binding affinity of IFIT1 for RNA oligonucleotides resembling the 5' ends of IAV gene segments. The affinity for 5'-ppp RNA was approximately 10-fold lower than that for non-2'-O-methylated (cap 0) RNA oligonucleotides. Based on this analysis, we conclude that IFIT1 is not a dominant restriction factor against negative-sense RNA viruses. Negative-sense RNA viruses, including influenza virus and Ebola virus, have been responsible for some of the most deadly outbreaks in recent history. The host interferon response and induction of antiviral genes contribute to the control of infections by these viruses. IFIT1 is highly induced after virus infection and reportedly has antiviral activity against several RNA and DNA viruses. However, its role in restricting infection by negative-sense RNA viruses remains unclear. In this study, we evaluated the ability of IFIT1 to inhibit negative-sense RNA virus replication and pathogenesis both in vitro and in vivo. Detailed cell culture and animal studies demonstrated that IFIT1 is not a dominant restriction factor against three different families of negative-sense RNA viruses. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Human and Murine IFIT1 Proteins Do Not Restrict Infection of Negative-Sense RNA Viruses of the Orthomyxoviridae, Bunyaviridae, and Filoviridae Families

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinto, Amelia K.; Williams, Graham D.; Szretter, Kristy J.

Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) is a host protein with reported cell-intrinsic antiviral activity against several RNA viruses. The proposed basis for the activity against negative-sense RNA viruses is the binding to exposed 5'-triphosphates (5'-ppp) on the genome of viral RNA. However, recent studies reported relatively low binding affinities of IFIT1 for 5'-ppp RNA, suggesting that IFIT1 may not interact efficiently with this moiety under physiological conditions. To evaluate the ability of IFIT1 to have an impact on negative-sense RNA viruses, we infectedIfit1 -/-and wild-type control mice and primary cells with four negative-sense RNA viruses (influenza A virusmore » [IAV], La Crosse virus [LACV], Oropouche virus [OROV], and Ebola virus) corresponding to three distinct families. Unexpectedly, a lack ofIfit1gene expression did not result in increased infection by any of these viruses in cell culture. Analogously, morbidity, mortality, and viral burdens in tissues were identical betweenIfit1 -/-and control mice after infection with IAV, LACV, or OROV. Finally, deletion of the human IFIT1 protein in A549 cells did not affect IAV replication or infection, and reciprocally, ectopic expression of IFIT1 in HEK293T cells did not inhibit IAV infection. To explain the lack of antiviral activity against IAV, we measured the binding affinity of IFIT1 for RNA oligonucleotides resembling the 5' ends of IAV gene segments. The affinity for 5'-ppp RNA was approximately 10-fold lower than that for non-2'-O-methylated (cap 0) RNA oligonucleotides. Based on this analysis, we conclude that IFIT1 is not a dominant restriction factor against negative-sense RNA viruses. IMPORTANCENegative-sense RNA viruses, including influenza virus and Ebola virus, have been responsible for some of the most deadly outbreaks in recent history. The host interferon response and induction of antiviral genes contribute to the control of infections by these viruses. IFIT1 is highly induced after virus infection and reportedly has antiviral activity against several RNA and DNA viruses. However, its role in restricting infection by negative-sense RNA viruses remains unclear. In this study, we evaluated the ability of IFIT1 to inhibit negative-sense RNA virus replication and pathogenesis bothin vitroandin vivo. Detailed cell culture and animal studies demonstrated that IFIT1 is not a dominant restriction factor against three different families of negative-sense RNA viruses.« less

The Bartonella quintana Extracytoplasmic Function Sigma Factor RpoE Has a Role in Bacterial Adaptation to the Arthropod Vector Environment

PubMed Central

Abromaitis, Stephanie

2013-01-01

Bartonella quintana is a vector-borne bacterial pathogen that causes fatal disease in humans. During the infectious cycle, B. quintana transitions from the hemin-restricted human bloodstream to the hemin-rich body louse vector. Because extracytoplasmic function (ECF) sigma factors often regulate adaptation to environmental changes, we hypothesized that a previously unstudied B. quintana ECF sigma factor, RpoE, is involved in the transition from the human host to the body louse vector. The genomic context of B. quintana rpoE identified it as a member of the ECF15 family of sigma factors found only in alphaproteobacteria. ECF15 sigma factors are believed to be the master regulators of the general stress response in alphaproteobacteria. In this study, we examined the B. quintana RpoE response to two stressors that are encountered in the body louse vector environment, a decreased temperature and an increased hemin concentration. We determined that the expression of rpoE is significantly upregulated at the body louse (28°C) versus the human host (37°C) temperature. rpoE expression also was upregulated when B. quintana was exposed to high hemin concentrations. In vitro and in vivo analyses demonstrated that RpoE function is regulated by a mechanism involving the anti-sigma factor NepR and the response regulator PhyR. The ΔrpoE ΔnepR mutant strain of B. quintana established that RpoE-mediated transcription is important in mediating the tolerance of B. quintana to high hemin concentrations. We present the first analysis of an ECF15 sigma factor in a vector-borne human pathogen and conclude that RpoE has a role in the adaptation of B. quintana to the hemin-rich arthropod vector environment. PMID:23564167

Identification of Loci Controlling Restriction of Parasite Growth in Experimental Taenia crassiceps Cysticercosis

PubMed Central

Fortin, Anny; Sciutto-Conde, Edda; Fragoso-González, Gladis; Gros, Philippe; Aguilar-Delfin, Irma

2011-01-01

Human neurocysticercosis (NC) caused by Taenia solium is a parasitic disease of the central nervous system that is endemic in many developing countries. In this study, a genetic approach using the murine intraperitoneal cysticercosis caused by the related cestode Taenia crassiceps was employed to identify host factors that regulate the establishment and proliferation of the parasite. A/J mice are permissive to T. crassiceps infection while C57BL/6J mice (B6) are comparatively restrictive, with a 10-fold difference in numbers of peritoneal cysticerci recovered 30 days after infection. The genetic basis of this inter-strain difference was explored using 34 AcB/BcA recombinant congenic strains derived from A/J and B6 progenitors, that were phenotyped for T. crassiceps replication. In agreement with their genetic background, most AcB strains (A/J-derived) were found to be permissive to infection while most BcA strains (B6-derived) were restrictive with the exception of a few discordant strains, together suggesting a possible simple genetic control. Initial haplotype association mapping using >1200 informative SNPs pointed to linkages on chromosomes 2 (proximal) and 6 as controlling parasite replication in the AcB/BcA panel. Additional linkage analysis by genome scan in informative [AcB55xDBA/2]F1 and F2 mice (derived from the discordant AcB55 strain), confirmed the effect of chromosome 2 on parasite replication, and further delineated a major locus (LOD = 4.76, p<0.01; peak marker D2Mit295, 29.7 Mb) that we designate Tccr1 (T. crassiceps cysticercosis restrictive locus 1). Resistance alleles at Tccr1 are derived from AcB55 and are inherited in a dominant fashion. Scrutiny of the minimal genetic interval reveals overlap of Tccr1 with other host resistance loci mapped to this region, most notably the defective Hc/C5 allele which segregates both in the AcB/BcA set and in the AcB55xDBA/2 cross. These results strongly suggest that the complement component 5 (C5) plays a critical role in early protective inflammatory response to infection with T. crassiceps. PMID:22206032

Phylogenetic relationships among anuran trypanosomes as revealed by riboprinting.

PubMed

Clark, C G; Martin, D S; Diamond, L S

1995-01-01

Twenty trypanosome isolates from Anura (frogs and toads) assigned to several species were characterized by riboprinting-restriction enzyme digestion of polymerase chain reaction amplified small subunit ribosomal RNA genes. Restriction site polymorphisms allowed distinction of all the recognized species and no intraspecific variation in riboprint patterns was detected. Phylogenetic reconstruction using parsimony and distance estimates based on restriction fragment comigration showed Trypanosoma chattoni to be only distantly related to the other species, while T. ranarum and T. fallisi appear to be sister taxa despite showing non-overlapping host specificities.

Feline Immunodeficiency Virus Cross-Species Transmission: Implications for Emergence of New Lentiviral Infections.

PubMed

Lee, Justin; Malmberg, Jennifer L; Wood, Britta A; Hladky, Sahaja; Troyer, Ryan; Roelke, Melody; Cunningham, Mark; McBride, Roy; Vickers, Winston; Boyce, Walter; Boydston, Erin; Serieys, Laurel; Riley, Seth; Crooks, Kevin; VandeWoude, Sue

2017-03-01

Owing to a complex history of host-parasite coevolution, lentiviruses exhibit a high degree of species specificity. Given the well-documented viral archeology of human immunodeficiency virus (HIV) emergence following human exposures to simian immunodeficiency virus (SIV), an understanding of processes that promote successful cross-species lentiviral transmissions is highly relevant. We previously reported natural cross-species transmission of a subtype of feline immunodeficiency virus, puma lentivirus A (PLVA), between bobcats ( Lynx rufus ) and mountain lions ( Puma concolor ) for a small number of animals in California and Florida. In this study, we investigate host-specific selection pressures, within-host viral fitness, and inter- versus intraspecies transmission patterns among a larger collection of PLV isolates from free-ranging bobcats and mountain lions. Analyses of proviral and viral RNA levels demonstrate that PLVA fitness is severely restricted in mountain lions compared to that in bobcats. We document evidence of diversifying selection in three of six PLVA genomes from mountain lions, but we did not detect selection among 20 PLVA isolates from bobcats. These findings support the hypothesis that PLVA is a bobcat-adapted virus which is less fit in mountain lions and under intense selection pressure in the novel host. Ancestral reconstruction of transmission events reveals that intraspecific PLVA transmission has occurred among panthers ( Puma concolor coryi ) in Florida following the initial cross-species infection from bobcats. In contrast, interspecific transmission from bobcats to mountain lions predominates in California. These findings document outcomes of cross-species lentiviral transmission events among felids that compare to the emergence of HIV from nonhuman primates. IMPORTANCE Cross-species transmission episodes can be singular, dead-end events or can result in viral replication and spread in the new species. The factors that determine which outcome will occur are complex, and the risk of new virus emergence is therefore difficult to predict. We used molecular techniques to evaluate the transmission, fitness, and adaptation of puma lentivirus A (PLVA) between bobcats and mountain lions in two geographic regions. Our findings illustrate that mountain lion exposure to PLVA is relatively common but does not routinely result in communicable infections in the new host. This is attributed to efficient species barriers that largely prevent lentiviral adaptation. However, the evolutionary capacity for lentiviruses to adapt to novel environments may ultimately overcome host restriction mechanisms over time and under certain ecological circumstances. This phenomenon provides a unique opportunity to examine cross-species transmission events leading to new lentiviral emergence. Copyright © 2017 American Society for Microbiology.

Feline Immunodeficiency Virus Cross-Species Transmission: Implications for Emergence of New Lentiviral Infections

PubMed Central

Lee, Justin; Malmberg, Jennifer L.; Wood, Britta A.; Hladky, Sahaja; Troyer, Ryan; Roelke, Melody; Cunningham, Mark; McBride, Roy; Vickers, Winston; Boyce, Walter; Boydston, Erin; Serieys, Laurel; Riley, Seth; Crooks, Kevin

2016-01-01

ABSTRACT Owing to a complex history of host-parasite coevolution, lentiviruses exhibit a high degree of species specificity. Given the well-documented viral archeology of human immunodeficiency virus (HIV) emergence following human exposures to simian immunodeficiency virus (SIV), an understanding of processes that promote successful cross-species lentiviral transmissions is highly relevant. We previously reported natural cross-species transmission of a subtype of feline immunodeficiency virus, puma lentivirus A (PLVA), between bobcats (Lynx rufus) and mountain lions (Puma concolor) for a small number of animals in California and Florida. In this study, we investigate host-specific selection pressures, within-host viral fitness, and inter- versus intraspecies transmission patterns among a larger collection of PLV isolates from free-ranging bobcats and mountain lions. Analyses of proviral and viral RNA levels demonstrate that PLVA fitness is severely restricted in mountain lions compared to that in bobcats. We document evidence of diversifying selection in three of six PLVA genomes from mountain lions, but we did not detect selection among 20 PLVA isolates from bobcats. These findings support the hypothesis that PLVA is a bobcat-adapted virus which is less fit in mountain lions and under intense selection pressure in the novel host. Ancestral reconstruction of transmission events reveals that intraspecific PLVA transmission has occurred among panthers (Puma concolor coryi) in Florida following the initial cross-species infection from bobcats. In contrast, interspecific transmission from bobcats to mountain lions predominates in California. These findings document outcomes of cross-species lentiviral transmission events among felids that compare to the emergence of HIV from nonhuman primates. IMPORTANCE Cross-species transmission episodes can be singular, dead-end events or can result in viral replication and spread in the new species. The factors that determine which outcome will occur are complex, and the risk of new virus emergence is therefore difficult to predict. We used molecular techniques to evaluate the transmission, fitness, and adaptation of puma lentivirus A (PLVA) between bobcats and mountain lions in two geographic regions. Our findings illustrate that mountain lion exposure to PLVA is relatively common but does not routinely result in communicable infections in the new host. This is attributed to efficient species barriers that largely prevent lentiviral adaptation. However, the evolutionary capacity for lentiviruses to adapt to novel environments may ultimately overcome host restriction mechanisms over time and under certain ecological circumstances. This phenomenon provides a unique opportunity to examine cross-species transmission events leading to new lentiviral emergence. PMID:28003486

Aberrant epithelial differentiation by cigarette smoke dysregulates respiratory host defence.

PubMed

Amatngalim, Gimano D; Schrumpf, Jasmijn A; Dishchekenian, Fernanda; Mertens, Tinne C J; Ninaber, Dennis K; van der Linden, Abraham C; Pilette, Charles; Taube, Christian; Hiemstra, Pieter S; van der Does, Anne M

2018-04-01

It is currently unknown how cigarette smoke-induced airway remodelling affects highly expressed respiratory epithelial defence proteins and thereby mucosal host defence.Localisation of a selected set of highly expressed respiratory epithelial host defence proteins was assessed in well-differentiated primary bronchial epithelial cell (PBEC) cultures. Next, PBEC were cultured at the air-liquid interface, and during differentiation for 2-3 weeks exposed daily to whole cigarette smoke. Gene expression, protein levels and epithelial cell markers were subsequently assessed. In addition, functional activities and persistence of the cigarette smoke-induced effects upon cessation were determined.Expression of the polymeric immunoglobulin receptor, secretory leukocyte protease inhibitor and long and short PLUNC (palate, lung and nasal epithelium clone protein) was restricted to luminal cells and exposure of differentiating PBECs to cigarette smoke resulted in a selective reduction of the expression of these luminal cell-restricted respiratory host defence proteins compared to controls. This reduced expression was a consequence of cigarette smoke-impaired end-stage differentiation of epithelial cells, and accompanied by a significant decreased transepithelial transport of IgA and bacterial killing.These findings shed new light on the importance of airway epithelial cell differentiation in respiratory host defence and could provide an additional explanation for the increased susceptibility of smokers and patients with chronic obstructive pulmonary disease to respiratory infections. Copyright ©ERS 2018.

An investigation into the distribution, host-preference and population density of ixodid ticks affecting domestic animals in Bangladesh.

PubMed

Islam, M Khyrul; Alim, M Abdul; Tsuji, Naotoshi; Mondal, M Motahar Hussain

2006-01-01

To study the distribution, host-preference and population density of ixodid ticks in Bangladesh, an attempt was made to collect adult ticks from various host animals in three distinct topographic zones, viz. flood plains, hills and steppe 'Barind'. Five species of ixodid ticks were recorded, namely, Boophilus microplus (56.3%), Haemaphysalis bispinosa (11.3%), Rhipicephalus sanguineus (14.7%), Hyalomma anatolicum anatolicum (15.0%) and Amblyomma testudinarium (2.8%). The data showed that B. microplus occurred predominantly on cattle (42.4%). The other hosts involved were buffaloes (12.5%), goats (25.5%) and pigs (8.2%). H. bispinosa mostly parasitized goats (31.5%) rather than cattle (12.0%) and buffaloes (10.8%). R. sanguineus was principally a dog tick (27.4%) but also parasitized cattle (10.8%) and goats (6.8%). H. a. anatolicum was restricted to cattle (19.2%) and A. testudinarium was found on both cattle (4.4%) and pigs (2.3%). These results indicate that ixodid ticks are not strictly host-specific except for H. a. anatolicum. The population density of these ticks was significantly (p < 0.01) influenced by the changing of seasons. B. microplus, H. bispinosa and R. sanguineus were by far the most widely distributed species; the distribution of H. a. anatolicum was restricted to the steppe 'Barind tract' and A. testudinarium was found in the hilly regions only.

Sequestration of host-CD59 as potential immune evasion strategy of Trichomonas vaginalis.

PubMed

Ibáñez-Escribano, Alexandra; Nogal-Ruiz, Juan José; Pérez-Serrano, Jorge; Gómez-Barrio, Alicia; Escario, J Antonio; Alderete, J F

2015-09-01

Trichomonas vaginalis is known to evade complement-mediated lysis. Because the genome of T. vaginalis does not possess DNA sequence with homology to human protectin (CD59), a complement lysis restricting factor, we tested the hypothesis that host CD59 acquisition by T. vaginalis organisms mediates resistance to complement killing. This hypothesis was based on the fact that trichomonads are known to associate with host proteins. No CD59 was detected on the surface of T. vaginalis grown in serum-based medium using as probe anti-CD59 monoclonal antibody (MAb). We, therefore, infected mice intraperitoneally with live T. vaginalis, and trichomonads harvested from ascites were tested for binding of CD59. Immunofluorescence showed that parasites had surface CD59. Furthermore, as mouse erythrocytes (RBCs) possess membrane-associated CD59, and trichomonads use RBCs as a nutrient source, organisms were co-cultured with murine RBCs for one week. Parasites were shown to have detectable surface CD59. Importantly, live T. vaginalis with bound CD59 were compared with batch-grown parasites without surface-associated CD59 for sensitivity to complement in human serum. Trichomonads without surface-bound CD59 had a higher level of killing by complement than did parasites with surface CD59. These data show that host CD59 acquired onto the surface by live T. vaginalis may be an alternative mechanism for complement evasion. We describe a novel strategy by T. vaginalis consistent with host protein procurement by this parasite to evade the lytic action of complement. Copyright © 2015 Elsevier B.V. All rights reserved.

Role of the B Allele of Influenza A Virus Segment 8 in Setting Mammalian Host Range and Pathogenicity

PubMed Central

Turnbull, Matthew L.; Wise, Helen M.; Nicol, Marlynne Q.; Smith, Nikki; Dunfee, Rebecca L.; Beard, Philippa M.; Jagger, Brett W.; Ligertwood, Yvonne; Hardisty, Gareth R.; Xiao, Haixia; Benton, Donald J.; Coburn, Alice M.; Paulo, Joao A.; Gygi, Steven P.; McCauley, John W.; Taubenberger, Jeffery K.; Lycett, Samantha J.; Weekes, Michael P.; Dutia, Bernadette M.

2016-01-01

ABSTRACT Two alleles of segment 8 (NS) circulate in nonchiropteran influenza A viruses. The A allele is found in avian and mammalian viruses, but the B allele is viewed as being almost exclusively found in avian viruses. This might reflect the fact that one or both of its encoded proteins (NS1 and NEP) are maladapted for replication in mammalian hosts. To test this, a number of clade A and B avian virus-derived NS segments were introduced into human H1N1 and H3N2 viruses. In no case was the peak virus titer substantially reduced following infection of various mammalian cell types. Exemplar reassortant viruses also replicated to similar titers in mice, although mice infected with viruses with the avian virus-derived segment 8s had reduced weight loss compared to that achieved in mice infected with the A/Puerto Rico/8/1934 (H1N1) parent. In vitro, the viruses coped similarly with type I interferons. Temporal proteomics analysis of cellular responses to infection showed that the avian virus-derived NS segments provoked lower levels of expression of interferon-stimulated genes in cells than wild type-derived NS segments. Thus, neither the A nor the B allele of avian virus-derived NS segments necessarily attenuates virus replication in a mammalian host, although the alleles can attenuate disease. Phylogenetic analyses identified 32 independent incursions of an avian virus-derived A allele into mammals, whereas 6 introductions of a B allele were identified. However, A-allele isolates from birds outnumbered B-allele isolates, and the relative rates of Aves-to-Mammalia transmission were not significantly different. We conclude that while the introduction of an avian virus segment 8 into mammals is a relatively rare event, the dogma of the B allele being especially restricted is misleading, with implications in the assessment of the pandemic potential of avian influenza viruses. IMPORTANCE Influenza A virus (IAV) can adapt to poultry and mammalian species, inflicting a great socioeconomic burden on farming and health care sectors. Host adaptation likely involves multiple viral factors. Here, we investigated the role of IAV segment 8. Segment 8 has evolved into two distinct clades: the A and B alleles. The B-allele genes have previously been suggested to be restricted to avian virus species. We introduced a selection of avian virus A- and B-allele segment 8s into human H1N1 and H3N2 virus backgrounds and found that these reassortant viruses were fully competent in mammalian host systems. We also analyzed the currently available public data on the segment 8 gene distribution and found surprisingly little evidence for specific avian host restriction of the B-clade segment. We conclude that B-allele segment 8 genes are, in fact, capable of supporting infection in mammals and that they should be considered during the assessment of the pandemic risk of zoonotic influenza A viruses. PMID:27489273

Role of the B Allele of Influenza A Virus Segment 8 in Setting Mammalian Host Range and Pathogenicity.

PubMed

Turnbull, Matthew L; Wise, Helen M; Nicol, Marlynne Q; Smith, Nikki; Dunfee, Rebecca L; Beard, Philippa M; Jagger, Brett W; Ligertwood, Yvonne; Hardisty, Gareth R; Xiao, Haixia; Benton, Donald J; Coburn, Alice M; Paulo, Joao A; Gygi, Steven P; McCauley, John W; Taubenberger, Jeffery K; Lycett, Samantha J; Weekes, Michael P; Dutia, Bernadette M; Digard, Paul

2016-10-15

Two alleles of segment 8 (NS) circulate in nonchiropteran influenza A viruses. The A allele is found in avian and mammalian viruses, but the B allele is viewed as being almost exclusively found in avian viruses. This might reflect the fact that one or both of its encoded proteins (NS1 and NEP) are maladapted for replication in mammalian hosts. To test this, a number of clade A and B avian virus-derived NS segments were introduced into human H1N1 and H3N2 viruses. In no case was the peak virus titer substantially reduced following infection of various mammalian cell types. Exemplar reassortant viruses also replicated to similar titers in mice, although mice infected with viruses with the avian virus-derived segment 8s had reduced weight loss compared to that achieved in mice infected with the A/Puerto Rico/8/1934 (H1N1) parent. In vitro, the viruses coped similarly with type I interferons. Temporal proteomics analysis of cellular responses to infection showed that the avian virus-derived NS segments provoked lower levels of expression of interferon-stimulated genes in cells than wild type-derived NS segments. Thus, neither the A nor the B allele of avian virus-derived NS segments necessarily attenuates virus replication in a mammalian host, although the alleles can attenuate disease. Phylogenetic analyses identified 32 independent incursions of an avian virus-derived A allele into mammals, whereas 6 introductions of a B allele were identified. However, A-allele isolates from birds outnumbered B-allele isolates, and the relative rates of Aves-to-Mammalia transmission were not significantly different. We conclude that while the introduction of an avian virus segment 8 into mammals is a relatively rare event, the dogma of the B allele being especially restricted is misleading, with implications in the assessment of the pandemic potential of avian influenza viruses. Influenza A virus (IAV) can adapt to poultry and mammalian species, inflicting a great socioeconomic burden on farming and health care sectors. Host adaptation likely involves multiple viral factors. Here, we investigated the role of IAV segment 8. Segment 8 has evolved into two distinct clades: the A and B alleles. The B-allele genes have previously been suggested to be restricted to avian virus species. We introduced a selection of avian virus A- and B-allele segment 8s into human H1N1 and H3N2 virus backgrounds and found that these reassortant viruses were fully competent in mammalian host systems. We also analyzed the currently available public data on the segment 8 gene distribution and found surprisingly little evidence for specific avian host restriction of the B-clade segment. We conclude that B-allele segment 8 genes are, in fact, capable of supporting infection in mammals and that they should be considered during the assessment of the pandemic risk of zoonotic influenza A viruses. Copyright © 2016 Turnbull et al.

Role of ND10 nuclear bodies in the chromatin repression of HSV-1.

PubMed

Gu, Haidong; Zheng, Yi

2016-04-05

Herpes simplex virus (HSV) is a neurotropic virus that establishes lifelong latent infection in human ganglion sensory neurons. This unique life cycle necessitates an intimate relation between the host defenses and virus counteractions over the long course of infection. Two important aspects of host anti-viral defense, nuclear substructure restriction and epigenetic chromatin regulation, have been intensively studied in the recent years. Upon viral DNA entering the nucleus, components of discrete nuclear bodies termed nuclear domain 10 (ND10), converge at viral DNA and place restrictions on viral gene expression. Meanwhile the infected cell mobilizes its histones and histone-associated repressors to force the viral DNA into nucleosome-like structures and also represses viral transcription. Both anti-viral strategies are negated by various HSV countermeasures. One HSV gene transactivator, infected cell protein 0 (ICP0), is a key player in antagonizing both the ND10 restriction and chromatin repression. On one hand, ICP0 uses its E3 ubiquitin ligase activity to target major ND10 components for proteasome-dependent degradation and thereafter disrupts the ND10 nuclear bodies. On the other hand, ICP0 participates in de-repressing the HSV chromatin by changing histone composition or modification and therefore activates viral transcription. Involvement of a single viral protein in two seemingly different pathways suggests that there is coordination in host anti-viral defense mechanisms and also cooperation in viral counteraction strategies. In this review, we summarize recent advances in understanding the role of chromatin regulation and ND10 dynamics in both lytic and latent HSV infection. We focus on the new observations showing that ND10 nuclear bodies play a critical role in cellular chromatin regulation. We intend to find the connections between the two major anti-viral defense pathways, chromatin remodeling and ND10 structure, in order to achieve a better understanding of how host orchestrates a concerted defense and how HSV adapts with and overcomes the host immunity.

Comparative Genomics Evidence That Only Protein Toxins are Tagging Bad Bugs

PubMed Central

Georgiades, Kalliopi; Raoult, Didier

2011-01-01

The term toxin was introduced by Roux and Yersin and describes macromolecular substances that, when produced during infection or when introduced parenterally or orally, cause an impairment of physiological functions that lead to disease or to the death of the infected organism. Long after the discovery of toxins, early genetic studies on bacterial virulence demonstrated that removing a certain number of genes from pathogenic bacteria decreases their capacity to infect hosts. Each of the removed factors was therefore referred to as a “virulence factor,” and it was speculated that non-pathogenic bacteria lack such supplementary factors. However, many recent comparative studies demonstrate that the specialization of bacteria to eukaryotic hosts is associated with massive gene loss. We recently demonstrated that the only features that seem to characterize 12 epidemic bacteria are toxin–antitoxin (TA) modules, which are addiction molecules in host bacteria. In this study, we investigated if protein toxins are indeed the only molecules specific to pathogenic bacteria by comparing 14 epidemic bacterial killers (“bad bugs”) with their 14 closest non-epidemic relatives (“controls”). We found protein toxins in significantly more elevated numbers in all of the “bad bugs.” For the first time, statistical principal components analysis, including genome size, GC%, TA modules, restriction enzymes, and toxins, revealed that toxins are the only proteins other than TA modules that are correlated with the pathogenic character of bacteria. Moreover, intracellular toxins appear to be more correlated with the pathogenic character of bacteria than secreted toxins. In conclusion, we hypothesize that the only truly identifiable phenomena, witnessing the convergent evolution of the most pathogenic bacteria for humans are the loss of metabolic activities, i.e., the outcome of the loss of regulatory and transcription factors and the presence of protein toxins, alone, or coupled as TA modules. PMID:22919573

Concurrent micro-RNA mediated silencing of tick-borne flavivirus replication in tick vector and in the brain of vertebrate host.

PubMed

Tsetsarkin, Konstantin A; Liu, Guangping; Kenney, Heather; Hermance, Meghan; Thangamani, Saravanan; Pletnev, Alexander G

2016-09-13

Tick-borne viruses include medically important zoonotic pathogens that can cause life-threatening diseases. Unlike mosquito-borne viruses, whose impact can be restrained via mosquito population control programs, for tick-borne viruses only vaccination remains the reliable means of disease prevention. For live vaccine viruses a concern exists, that spillovers from viremic vaccinees could result in introduction of genetically modified viruses into sustainable tick-vertebrate host transmission cycle in nature. To restrict tick-borne flavivirus (Langat virus, LGTV) vector tropism, we inserted target sequences for tick-specific microRNAs (mir-1, mir-275 and mir-279) individually or in combination into several distant regions of LGTV genome. This caused selective attenuation of viral replication in tick-derived cells. LGTV expressing combinations of target sequences for tick- and vertebrate CNS-specific miRNAs were developed. The resulting viruses replicated efficiently and remained stable in simian Vero cells, which do not express these miRNAs, however were severely restricted to replicate in tick-derived cells. In addition, simultaneous dual miRNA targeting led to silencing of virus replication in live Ixodes ricinus ticks and abolished virus neurotropism in highly permissive newborn mice. The concurrent restriction of adverse replication events in vertebrate and invertebrate hosts will, therefore, ensure the environmental safety of live tick-borne virus vaccine candidates.

Sequential cloning of chromosomes

DOEpatents

Lacks, Sanford A.

1995-07-18

A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism's chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Komatsu, Tetsuro; Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575; Will, Hans

2016-04-22

Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions asmore » well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. - Highlights: • Host nuclear antiviral factors were analyzed upon adenovirus genome delivery. • Interferon treatments fail to permit PML nuclear bodies to target adenoviral genomes. • Neither Sp100A nor B targets adenoviral genomes despite potentially opposite roles. • The nuclear DNA sensor IFI16 does not target incoming adenoviral genomes. • PHF13/SPOC1 targets neither incoming adenoviral genomes nor genome-bound protein VII.« less

Relations of Environmental Factors with Mussel-Species Richness in the Neversink River, New York

USGS Publications Warehouse

Baldigo, Barry P.; Ernst, Anne G.; Schuler, George E.; Apse, Colin D.

2007-01-01

INTRODUCTION Declines in the distribution, abundance, and diversity of freshwater-mussel species (family Unionidae1) have been reported worldwide (Bogan, 1993; Strayer and Jirka, 1997). The principal causes of the observed declines are difficult to confirm, however, because only a few of the many factors that affect mussel-species populations have been identified (Strayer and Ralley, 1993; Strayer, 1999; Baldigo and others, 2003; Strayer and others, 2006). The Neversink River, which drains the Catskill Mountains in southeastern New York (fig. 1), contains seven species of mussels (Strayer and Ralley, 1991; Strayer and Jirka, 1997). Populations of the endangered dwarf wedgemussel (Alasmidonta heterodon) and the threatened swollen wedgemussel (Alasmidonta varicosa) coexist with other unionid mussels in the Neversink River (Strayer and Ralley, 1991, 1993; Baldigo and others, 2003). Dwarf wedgemussel populations had previously been found only downstream from the site of an abandoned dam in the lower part of the river at Cuddebackville (fig. 1), and swollen wedgemussels were only found in the lower and middle reaches of the river. The limited distribution of these two species suggests that they may be susceptible to local extinctions. The distribution of mussel populations can be limited by impoundments. Mussel larvae develop in species-specific host fish; thus, impoundments that restrict passage of these host fish also restrict the extent of mussels. The Neversink River is impounded by the Neversink Reservoir [241 square kilometers (km2)], a major source of drinking water for the City of New York, and was also impounded 50 km downstream by the Cuddebackville Dam until 2004, when the latter was removed by The Nature Conservancy (TNC) and the U.S. Army Corps of Engineers to improve fish passage. The removal of this dam has provided previously unavailable habitat for diadromous and other fish species that act as hosts for rare mussel species. In addition, releases from the Neversink Reservoir that mimic the river?s original flow patterns have recently been proposed by TNC and could benefit the established mussel populations and aquatic communities. The ability to protect mussel populations and the potential to increase mussel richness in the Neversink River is unknown, however, because the environmental factors that affect the seven mussel species are poorly defined, and the distribution of mussel beds is patchy and thus difficult to quantify. In 1997, the U.S. Geological Survey, in cooperation with TNC, began a 6-year study along the Neversink River and its tributaries to (1) document the current distribution of each mussel species, (2) assess environmental factors in relation to mussel-species richness and distribution, and (3) identify the factors that most strongly affect mussel populations and develop an equation that relates environmental factors to mussel-species richness. This report (a) summarizes the methods used to quantify or qualify environmental factors and mussel-species distribution and abundance, (b) presents a list of environmental factors that were correlated with mussel-species richness, and (c) offers an empirical model to predict richness of mussel species in benthic communities throughout the basin.

Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection.

PubMed

Li, Sam X; Barrett, Bradley S; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L

2016-02-05

Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation.

Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection

PubMed Central

Li, Sam X.; Barrett, Bradley S.; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J.; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L.

2016-01-01

Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation. PMID:26846717

Vectors for co-expression of an unrestricted number of proteins

PubMed Central

Scheich, Christoph; Kümmel, Daniel; Soumailakakis, Dimitri; Heinemann, Udo; Büssow, Konrad

2007-01-01

A vector system is presented that allows generation of E. coli co-expression clones by a standardized, robust cloning procedure. The number of co-expressed proteins is not limited. Five ‘pQLink’ vectors for expression of His-tag and GST-tag fusion proteins as well as untagged proteins and for cloning by restriction enzymes or Gateway cloning were generated. The vectors allow proteins to be expressed individually; to achieve co-expression, two pQLink plasmids are combined by ligation-independent cloning. pQLink co-expression plasmids can accept an unrestricted number of genes. As an example, the co-expression of a heterotetrameric human transport protein particle (TRAPP) complex from a single plasmid, its isolation and analysis of its stoichiometry are shown. pQLink clones can be used directly for pull-down experiments if the proteins are expressed with different tags. We demonstrate pull-down experiments of human valosin-containing protein (VCP) with fragments of the autocrine motility factor receptor (AMFR). The cloning method avoids PCR or gel isolation of restriction fragments, and a single resistance marker and origin of replication are used, allowing over-expression of rare tRNAs from a second plasmid. It is expected that applications are not restricted to bacteria, but could include co-expression in other hosts such as Bacluovirus/insect cells. PMID:17311810

Apobec 3G efficiently reduces infectivity of the human exogenous gammaretrovirus XMRV.

PubMed

Stieler, Kristin; Fischer, Nicole

2010-07-23

The human exogenous gammaretrovirus XMRV is thought to be implicated in prostate cancer and chronic fatigue syndrome. Besides pressing epidemiologic questions, the elucidation of the tissue and cell tropism of the virus, as well as its sensitivity to retroviral restriction factors is of fundamental importance. The Apobec3 (A3) proteins, a family of cytidine deaminases, are one important group of host proteins that control primary infection and efficient viral spread. Here we demonstrate that XMRV is resistant to human Apobec 3B, 3C and 3F, while being highly susceptible to the human A3G protein, a factor which is known to confer antiviral activity against most retroviruses. We show that XMRV as well as MoMLV virions package Apobec proteins independent of their specific restriction activity. hA3G was found to be a potent inhibitor of XMRV as well as of MoMLV infectivity. In contrast to MoMLV, XMRV infection can also be partially reduced by low concentrations of mA3. Interestingly, established prostate cancer cell lines, which are highly susceptible to XMRV infection, do not or only weakly express hA3G. Our findings confirm and extend recently published data that show restriction of XMRV infection by hA3G. The results will be of value to explore which cells are infected with XMRV and efficiently support viral spread in vivo. Furthermore, the observation that XMRV infection can be reduced by mA3 is of interest with regard to the current natural reservoir of XMRV infection.

Avian colibacillosis: still many black holes.

PubMed

Guabiraba, Rodrigo; Schouler, Catherine

2015-08-01

Avian pathogenic Escherichia coli (APEC) strains cause severe respiratory and systemic diseases, threatening food security and avian welfare worldwide. Intensification of poultry production and the quick expansion of free-range production systems will increase the incidence of colibacillosis through greater exposure of birds to pathogens and stress. Therapy is mainly based on antibiotherapy and current vaccines have poor efficacy. Serotyping remains the most frequently used diagnostic method, only allowing the identification of a limited number of APEC strains. Several studies have demonstrated that the most common virulence factors studied in APEC are all rarely present in the same isolate, showing that APEC strains constitute a heterogeneous group. Different isolates may harbor different associations of virulence factors, each one able to induce colibacillosis. Despite its economical relevance, pathogenesis of colibacillosis is poorly understood. Our knowledge on the host response to APEC is based on very descriptive studies, mostly restricted to bacteriological and histopathological analysis of infected organs such as lungs. Furthermore, only a small number of APEC isolates have been used in experimental studies. In the present review, we discuss current knowledge on APEC diversity and virulence, including host response to infection and the associated inflammatory response with a focus on pulmonary colibacillosis. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Factors affecting host range in a generalist seed pathogen of semi-arid shrublands

Treesearch

Julie Beckstead; Susan E. Meyer; Kurt O. Reinhart; Kellene M. Bergen; Sandra R. Holden; Heather F. Boekweg

2014-01-01

Generalist pathogens can exhibit differential success on different hosts, resulting in complex host range patterns. Several factors operate to reduce realized host range relative to potential host range, particularly under field conditions. We explored factors influencing host range of the naturally occurring generalist ascomycete grass seed pathogen Pyrenophora...

Deciphering the landscape of host barriers to Listeria monocytogenes infection.

PubMed

Zhang, Ting; Abel, Sören; Abel Zur Wiesch, Pia; Sasabe, Jumpei; Davis, Brigid M; Higgins, Darren E; Waldor, Matthew K

2017-06-13

Listeria monocytogenes is a common food-borne pathogen that can disseminate from the intestine and infect multiple organs. Here, we used sequence tag-based analysis of microbial populations (STAMP) to investigate L monocytogenes population dynamics during infection. We created a genetically barcoded library of murinized L monocytogenes and then used deep sequencing to track the pathogen's dissemination routes and quantify its founding population ( N b ) sizes in different organs. We found that the pathogen disseminates from the gastrointestinal tract to distal sites through multiple independent routes and that N b sizes vary greatly among tissues, indicative of diverse host barriers to infection. Unexpectedly, comparative analyses of sequence tags revealed that fecally excreted organisms are largely derived from the very small number of L. monocytogenes cells that colonize the gallbladder. Immune depletion studies suggest that distinct innate immune cells restrict the pathogen's capacity to establish replicative niches in the spleen and liver. Finally, studies in germ-free mice suggest that the microbiota plays a critical role in the development of the splenic, but not the hepatic, barriers that prevent L. monocytogenes from seeding these organs. Collectively, these observations illustrate the potency of the STAMP approach to decipher the impact of host factors on population dynamics of pathogens during infection.

Functionality of resistance gene Hero, which controls plant root-infecting potato cyst nematodes, in leaves of tomato.

PubMed

Poch, H L Cabrera; López, R H Manzanilla; Kanyuka, K

2006-07-01

The expression of host genomes is modified locally by root endoparasitic nematode secretions to induce the development of complex cellular structures referred as feeding sites. In compatible interactions, the feeding sites provide the environment and nutrients for the completion of the nematode's life cycle, whereas in an incompatible (resistant) interaction, the host immune system triggers a plant cell death programme, often in the form of a hypersensitive reaction, which restricts nematode reproduction. These processes have been studied in great detail in organ tissues normally infected by these nematodes: the roots. Here we show that host leaves can support a similar set of programmed developmental events in the potato cyst nematode Globodera rostochiensis life cycle that are typical of the root-invading nematodes. We also show that a gene-for-gene type specific disease resistance that is effective against potato cyst nematodes (PCN) in roots also operates in leaves: the expression of the resistance (R) gene Hero and members of its gene family in leaves correlates with the elicitation of a hypersensitive response only during the incompatible interaction. These findings, and the ability to isolate RNA from relevant parasitic stages of the nematode, may have significant implications for the identification of nematode factors involved in incompatible interactions.

Deciphering the landscape of host barriers to Listeria monocytogenes infection

PubMed Central

Zhang, Ting; Abel, Sören; Abel zur Wiesch, Pia; Sasabe, Jumpei; Davis, Brigid M.; Higgins, Darren E.; Waldor, Matthew K.

2017-01-01

Listeria monocytogenes is a common food-borne pathogen that can disseminate from the intestine and infect multiple organs. Here, we used sequence tag-based analysis of microbial populations (STAMP) to investigate L. monocytogenes population dynamics during infection. We created a genetically barcoded library of murinized L. monocytogenes and then used deep sequencing to track the pathogen’s dissemination routes and quantify its founding population (Nb) sizes in different organs. We found that the pathogen disseminates from the gastrointestinal tract to distal sites through multiple independent routes and that Nb sizes vary greatly among tissues, indicative of diverse host barriers to infection. Unexpectedly, comparative analyses of sequence tags revealed that fecally excreted organisms are largely derived from the very small number of L. monocytogenes cells that colonize the gallbladder. Immune depletion studies suggest that distinct innate immune cells restrict the pathogen’s capacity to establish replicative niches in the spleen and liver. Finally, studies in germ-free mice suggest that the microbiota plays a critical role in the development of the splenic, but not the hepatic, barriers that prevent L. monocytogenes from seeding these organs. Collectively, these observations illustrate the potency of the STAMP approach to decipher the impact of host factors on population dynamics of pathogens during infection. PMID:28559314

Purification and proteomics of pathogen-modified vacuoles and membranes

PubMed Central

Herweg, Jo-Ana; Hansmeier, Nicole; Otto, Andreas; Geffken, Anna C.; Subbarayal, Prema; Prusty, Bhupesh K.; Becher, Dörte; Hensel, Michael; Schaible, Ulrich E.; Rudel, Thomas; Hilbi, Hubert

2015-01-01

Certain pathogenic bacteria adopt an intracellular lifestyle and proliferate in eukaryotic host cells. The intracellular niche protects the bacteria from cellular and humoral components of the mammalian immune system, and at the same time, allows the bacteria to gain access to otherwise restricted nutrient sources. Yet, intracellular protection and access to nutrients comes with a price, i.e., the bacteria need to overcome cell-autonomous defense mechanisms, such as the bactericidal endocytic pathway. While a few bacteria rupture the early phagosome and escape into the host cytoplasm, most intracellular pathogens form a distinct, degradation-resistant and replication-permissive membranous compartment. Intracellular bacteria that form unique pathogen vacuoles include Legionella, Mycobacterium, Chlamydia, Simkania, and Salmonella species. In order to understand the formation of these pathogen niches on a global scale and in a comprehensive and quantitative manner, an inventory of compartment-associated host factors is required. To this end, the intact pathogen compartments need to be isolated, purified and biochemically characterized. Here, we review recent progress on the isolation and purification of pathogen-modified vacuoles and membranes, as well as their proteomic characterization by mass spectrometry and different validation approaches. These studies provide the basis for further investigations on the specific mechanisms of pathogen-driven compartment formation. PMID:26082896

Restriction of a bacteriophage of Streptomyces albus G involving endonuclease SalI.

PubMed Central

Chater, K F; Wilde, L C

1976-01-01

The bacteriophage Pa16, isolated from soil on Streptomyces albus G, was restricted when transferred from an alternative host back to S. albus G. Extracted unmodified Pa16 deoxyribonucleic acid was cleaved at a single site by a cell-free extract of S. albus G. Fractions cleaving Pal6 deoxyribonucleic acid contained the endonuclease SalI first described by J. Arrand, P. Myers, and R. J. Roberts (unpublished data). A mutant of S. albus G was isolated which was defective in both restriction and modification of Pal6. This mutant lacked SalI activity. It is concluded that SalI is the agent of restriction of Pal6 by S. albus G. Images PMID:977549

Identification of HNRNPK as Regulator of Hepatitis C Virus Particle Production

PubMed Central

Poenisch, Marion; Metz, Philippe; Blankenburg, Hagen; Ruggieri, Alessia; Lee, Ji-Young; Rupp, Daniel; Rebhan, Ilka; Diederich, Kathrin; Kaderali, Lars; Domingues, Francisco S.; Albrecht, Mario; Lohmann, Volker; Erfle, Holger; Bartenschlager, Ralf

2015-01-01

Hepatitis C virus (HCV) is a major cause of chronic liver disease affecting around 130 million people worldwide. While great progress has been made to define the principle steps of the viral life cycle, detailed knowledge how HCV interacts with its host cells is still limited. To overcome this limitation we conducted a comprehensive whole-virus RNA interference-based screen and identified 40 host dependency and 16 host restriction factors involved in HCV entry/replication or assembly/release. Of these factors, heterogeneous nuclear ribonucleoprotein K (HNRNPK) was found to suppress HCV particle production without affecting viral RNA replication. This suppression of virus production was specific to HCV, independent from assembly competence and genotype, and not found with the related Dengue virus. By using a knock-down rescue approach we identified the domains within HNRNPK required for suppression of HCV particle production. Importantly, HNRNPK was found to interact specifically with HCV RNA and this interaction was impaired by mutations that also reduced the ability to suppress HCV particle production. Finally, we found that in HCV-infected cells, subcellular distribution of HNRNPK was altered; the protein was recruited to sites in close proximity of lipid droplets and colocalized with core protein as well as HCV plus-strand RNA, which was not the case with HNRNPK variants unable to suppress HCV virion formation. These results suggest that HNRNPK might determine efficiency of HCV particle production by limiting the availability of viral RNA for incorporation into virions. This study adds a new function to HNRNPK that acts as central hub in the replication cycle of multiple other viruses. PMID:25569684

Novel, host-restricted genotypes of Bordetella bronchiseptica associated with phocine respiratory tract isolates.

PubMed

Register, Karen B; Ivanov, Yury V; Harvill, Eric T; Davison, Nick; Foster, Geoffrey

2015-03-01

During a succession of phocine morbillivirus outbreaks spanning the past 25 years, Bordetella bronchiseptica was identified as a frequent secondary invader and cause of death. The goal of this study was to evaluate genetic diversity and the molecular basis for host specificity among seal isolates from these outbreaks. MLST and PvuII ribotyping of 54 isolates from Scottish, English or Danish coasts of the Atlantic or North Sea revealed a single, host-restricted genotype. A single, novel genotype, unique from that of the Atlantic and North Sea isolates, was found in isolates from an outbreak in the Caspian Sea. Phylogenetic analysis based either on MLST sequence, ribotype patterns or genome-wide SNPs consistently placed both seal-specific genotypes within the same major clade but indicates a distinct evolutionary history for each. An additional isolate from the intestinal tract of a seal on the south-west coast of England has a genotype otherwise found in rabbit, guinea pig and pig isolates. To investigate the molecular basis for host specificity, DNA and predicted protein sequences of virulence genes that mediate host interactions were used in comparisons between a North Sea isolate, a Caspian Sea isolate and each of their closest relatives as inferred from genome-wide SNP analysis. Despite their phylogenetic divergence, fewer nucleotide and amino acid substitutions were found in comparisons of the two seal isolates than in comparisons with closely related strains. These data indicate isolates of B. bronchiseptica associated with respiratory disease in seals comprise unique, host-adapted and highly clonal populations. © 2015 The Authors.

Functions, structure, and read-through alternative splicing of feline APOBEC3 genes

PubMed Central

Münk, Carsten; Beck, Thomas; Zielonka, Jörg; Hotz-Wagenblatt, Agnes; Chareza, Sarah; Battenberg, Marion; Thielebein, Jens; Cichutek, Klaus; Bravo, Ignacio G; O'Brien, Stephen J; Lochelt, Martin; Yuhki, Naoya

2008-01-01

Background Over the past years a variety of host restriction genes have been identified in human and mammals that modulate retrovirus infectivity, replication, assembly, and/or cross-species transmission. Among these host-encoded restriction factors, the APOBEC3 (A3; apolipoprotein B mRNA-editing catalytic polypeptide 3) proteins are potent inhibitors of retroviruses and retrotransposons. While primates encode seven of these genes (A3A to A3H), rodents carry only a single A3 gene. Results Here we identified and characterized several A3 genes in the genome of domestic cat (Felis catus) by analyzing the genomic A3 locus. The cat genome presents one A3H gene and three very similar A3C genes (a-c), probably generated after two consecutive gene duplications. In addition to these four one-domain A3 proteins, a fifth A3, designated A3CH, is expressed by read-through alternative splicing. Specific feline A3 proteins selectively inactivated only defined genera of feline retroviruses: Bet-deficient feline foamy virus was mainly inactivated by feA3Ca, feA3Cb, and feA3Cc, while feA3H and feA3CH were only weakly active. The infectivity of Vif-deficient feline immunodeficiency virus and feline leukemia virus was reduced only by feA3H and feA3CH, but not by any of the feA3Cs. Within Felidae, A3C sequences show significant adaptive selection, but unexpectedly, the A3H sequences present more sites that are under purifying selection. Conclusion Our data support a complex evolutionary history of expansion, divergence, selection and individual extinction of antiviral A3 genes that parallels the early evolution of Placentalia, becoming more intricate in taxa in which the arms race between host and retroviruses is harsher. PMID:18315870

DNET: A communications facility for distributed heterogeneous computing

NASA Technical Reports Server (NTRS)

Tole, John; Nagappan, S.; Clayton, J.; Ruotolo, P.; Williamson, C.; Solow, H.

1989-01-01

This document describes DNET, a heterogeneous data communications networking facility. DNET allows programs operating on hosts on dissimilar networks to communicate with one another without concern for computer hardware, network protocol, or operating system differences. The overall DNET network is defined as the collection of host machines/networks on which the DNET software is operating. Each underlying network is considered a DNET 'domain'. Data communications service is provided between any two processes on any two hosts on any of the networks (domains) that may be reached via DNET. DNET provides protocol transparent, reliable, streaming data transmission between hosts (restricted, initially to DECnet and TCP/IP networks). DNET also provides variable length datagram service with optional return receipts.

Strategies of Vibrio parahaemolyticus to acquire nutritional iron during host colonization

PubMed Central

León-Sicairos, Nidia; Angulo-Zamudio, Uriel A.; de la Garza, Mireya; Velázquez-Román, Jorge; Flores-Villaseñor, Héctor M.; Canizalez-Román, Adrian

2015-01-01

Iron is an essential element for the growth and development of virtually all living organisms. As iron acquisition is critical for the pathogenesis, a host defense strategy during infection is to sequester iron to restrict the growth of invading pathogens. To counteract this strategy, bacteria such as Vibrio parahaemolyticus have adapted to such an environment by developing mechanisms to obtain iron from human hosts. This review focuses on the multiple strategies employed by V. parahaemolyticus to obtain nutritional iron from host sources. In these strategies are included the use of siderophores and xenosiderophores, proteases and iron-protein receptor. The host sources used by V. parahaemolyticus are the iron-containing proteins transferrin, hemoglobin, and hemin. The implications of iron acquisition systems in the virulence of V. parahaemolyticus are also discussed. PMID:26217331

Ancestral Mutations Acquired in Refrex-1, a Restriction Factor against Feline Retroviruses, during its Cooption and Domestication

PubMed Central

Ito, Jumpei; Baba, Takuya; Kawasaki, Junna

2015-01-01

ABSTRACT Endogenous retroviruses (ERVs) are remnants of ancestral retroviral infections of germ cells. Retroviral endogenization is an adaptation process for the host genome, and ERVs are gradually attenuated or inactivated by mutation. However, some ERVs that have been “domesticated” by their hosts eventually gain physiological functions, such as placentation or viral resistance. We previously reported the discovery of Refrex-1, a soluble antiretroviral factor in domestic cats that specifically inhibits infection by feline leukemia virus subgroup D (FeLV-D), a chimeric virus of FeLV, and a feline ERV, ERV-DC. Refrex-1 is a truncated envelope protein (Env) encoded by both ERV-DC7 and ERV-DC16 proviral loci. Here, we reconstituted ancestral and functional Env from ERV-DC7 and ERV-DC16 envelope genes (env) by inducing reverse mutations. Unexpectedly, ERV-DC7 and ERV-DC16 full-length Env (ERV-DC7 fl and ERV-DC16 fl), reconstructed by removing stop codons, did not produce infectious viral particles. ERV-DC7 fl and ERV-DC16 fl were highly expressed in cells but were not cleaved into surface subunits (SU) and transmembrane subunits, nor were they incorporated into virions. G407R/N427I-A429T and Y431D substitutions within the SU C-terminal domain of ERV-DC7 fl and ERV-DC16 fl, respectively, caused these dysfunctions. The residues glycine 407 and tyrosine 431 are relatively conserved among infectious gammaretroviruses, and their substitution causes the same dysfunctions as the tested retroviruses. Our results reveal that specific mutations within the SU C-terminal domain suppressed Env cleavage and incorporation into virions and indicate that these mutations contributed to the domestication of Refrex-1 through multistep events that occurred in the postintegration period. IMPORTANCE Domestic cats are colonized with various exogenous retroviruses (exRVs), such as feline leukemia virus (FeLV), and their genomes contain numerous ERVs, some of which are replication-competent proviruses. The feline hosts, exRVs, and ERVs have complicated genetic interactions and provide an interesting field model for triangular relationships: recombination between FeLV and ERV-DC, which is a feline ERV, generated FeLV-D, a chimeric virus, and FeLV-D is restricted by Refrex-1, an antiretroviral factor corresponding to truncated Env of ERV-DC7 and ERV-DC16. Here, we reconstructed ancestral, functional Env from ERV-DC7 and ERV-DC16 env by inducing reverse mutations to elucidate how Refrex-1 was generated from its ancestor. Our results reveal that they were repeatedly inactivated by mutations preventing Env maturation. Our results provide insights into how ERVs were “domesticated” by their hosts and identify the mutations that mediated these evolutions. Notably, experiments that restore inactivated ERVs might uncover previously unrecognized features or properties of retroviruses. PMID:26581999

Innate immune restriction and antagonism of viral RNA lacking 2'-O methylation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hyde, Jennifer L.; Diamond, Michael S., E-mail: diamond@borcim.wustl.edu; Molecular Microbiology, Washington University School of Medicine, St Louis., MO 63110

N-7 and 2′-O methylation of host cell mRNA occurs in the nucleus and results in the generation of cap structures (cap 0, m{sup 7}GpppN; cap 1, m{sup 7}GpppNm) that control gene expression by modulating nuclear export, splicing, turnover, and protein synthesis. Remarkably, RNA cap modification also contributes to mammalian cell host defense as viral RNA lacking 2′-O methylation is sensed and inhibited by IFIT1, an interferon (IFN) stimulated gene (ISG). Accordingly, pathogenic viruses that replicate in the cytoplasm have evolved mechanisms to circumvent IFIT1 restriction and facilitate infection of mammalian cells. These include: (a) generating cap 1 structures on theirmore » RNA through cap-snatching or virally-encoded 2′-O methyltransferases, (b) using cap-independent means of translation, or (c) using RNA secondary structural motifs to antagonize IFIT1 binding. This review will discuss new insights as to how specific modifications at the 5′-end of viral RNA modulate host pathogen recognition responses to promote infection and disease.« less

[Legal aspects of Web 2.0 in the health field].

PubMed

Beslay, Nathalie; Jeunehomme, Marie

2009-10-01

Web 2.0 sites are considered to be hosting providers and not publishers of user-generated content. The liability of hosting providers' liability is defined by the law enacted on June 21, 2004, on confidence in the digital economy. Hosting providers must promptly remove the information they host or make its access impossible once they are informed of its illegality. They are required to obtain and retain data to enable identification of any person who has contributed to content hosted by them. The liability of hosting providers has arisen in numerous disputes about user-produced content in various situations (discussion lists, blogs, etc.). The National Board of Physicians has developed specific ethical guidelines for web sites devoted to health issues and specifically for physician-authored content. The National Board of Physicians acknowledges that physicians can present themselves, their office, and their specific practice on their web site, notwithstanding any restrictions otherwise applicable to advertising.

Seroprevalence and risk factors associated with exposure of water buffalo (Bubalus bubalis) to Neospora caninum in northeast Thailand.

PubMed

Kengradomkij, Chanya; Inpankaew, Tawin; Kamyingkird, Ketsarin; Wongpanit, Kannika; Wongnakphet, Sirichai; Mitchell, Thomas J; Xuan, Xuenan; Igarashi, Ikuo; Jittapalapong, Sathaporn; Stich, Roger W

2015-01-15

Water buffalo are important draft animals for agriculture in resource-restricted areas worldwide. Water buffalo were shown to be experimentally susceptible to infection with Neospora caninum, potentially affected by neosporosis, and naturally exposed to the parasite in Asia. Although enzootic to Thailand, the distribution of N. caninum among Thai water buffalo is unclear. The objectives of this study were to determine the seroprevalence of N. caninum among water buffalo of northeast Thailand and to identify risk factors associated with their exposure to N. caninum. Sera from 628 water buffalo from 288 farms were tested with an indirect fluorescent antibody test (IFAT). A total of 57 samples from 48 herds contained antibodies to N. caninum, indicating overall seroprevalence of 9.1% and 16.7% among individual animals and herds, respectively. The overall seroprevalence was highest in provinces located in the Khorat Basin in the southern part of the region tested. Host age was also associated with seroprevalence, with the greatest seroprevalence (16.1%) among buffalo over 10 years of age, followed by 5-10 years of age (13.4%), 3-5 years (9.2%), and less than 3 years (1.2%). These results collectively suggested that horizontal transmission from canine definitive hosts was an important route of water buffalo exposure to N. caninum. These results also verified the importance of risk factor analysis for effective bovine neosporosis control strategies at the local level. Copyright © 2014 Elsevier B.V. All rights reserved.

pelo Is Required for High Efficiency Viral Replication

PubMed Central

Wu, Xiurong; He, Wan-Ting; Tian, Shuye; Meng, Dan; Li, Yuanyue; Chen, Wanze; Li, Lisheng; Tian, Lili; Zhong, Chuan-Qi; Han, Felicia; Chen, Jianming; Han, Jiahuai

2014-01-01

Viruses hijack host factors for their high speed protein synthesis, but information about these factors is largely unknown. In searching for genes that are involved in viral replication, we carried out a forward genetic screen for Drosophila mutants that are more resistant or sensitive to Drosophila C virus (DCV) infection-caused death, and found a virus-resistant line in which the expression of pelo gene was deficient. Our mechanistic studies excluded the viral resistance of pelo deficient flies resulting from the known Drosophila anti-viral pathways, and revealed that pelo deficiency limits the high level synthesis of the DCV capsid proteins but has no or very little effect on the expression of some other viral proteins, bulk cellular proteins, and transfected exogenous genes. The restriction of replication of other types of viruses in pelo deficient flies was also observed, suggesting pelo is required for high level production of capsids of all kinds of viruses. We show that both pelo deficiency and high level DCV protein synthesis increase aberrant 80S ribosomes, and propose that the preferential requirement of pelo for high level synthesis of viral capsids is at least partly due to the role of pelo in dissociation of stalled 80S ribosomes and clearance of aberrant viral RNA and proteins. Our data demonstrated that pelo is a host factor that is required for high efficiency translation of viral capsids and targeting pelo could be a strategy for general inhibition of viral infection. PMID:24722736

Host compatibility rather than vector–host-encounter rate determines the host range of avian Plasmodium parasites

PubMed Central

Medeiros, Matthew C. I.; Hamer, Gabriel L.; Ricklefs, Robert E.

2013-01-01

Blood-feeding arthropod vectors are responsible for transmitting many parasites between vertebrate hosts. While arthropod vectors often feed on limited subsets of potential host species, little is known about the extent to which this influences the distribution of vector-borne parasites in some systems. Here, we test the hypothesis that different vector species structure parasite–host relationships by restricting access of certain parasites to a subset of available hosts. Specifically, we investigate how the feeding patterns of Culex mosquito vectors relate to distributions of avian malaria parasites among hosts in suburban Chicago, IL, USA. We show that Plasmodium lineages, defined by cytochrome b haplotypes, are heterogeneously distributed across avian hosts. However, the feeding patterns of the dominant vectors (Culex restuans and Culex pipiens) are similar across these hosts, and do not explain the distributions of Plasmodium parasites. Phylogenetic similarity of avian hosts predicts similarity in their Plasmodium parasites. This effect was driven primarily by the general association of Plasmodium parasites with particular host superfamilies. Our results suggest that a mosquito-imposed encounter rate does not limit the distribution of avian Plasmodium parasites across hosts. This implies that compatibility between parasites and their avian hosts structure Plasmodium host range. PMID:23595266

IFN-λ prevents influenza virus spread from the upper airways to the lungs and limits virus transmission

PubMed Central

Ye, Liang; Schwaderlapp, Marilena; Gad, Hans Henrik; Hartmann, Rune; Garcin, Dominique; Mahlakõiv, Tanel

2018-01-01

Host factors restricting the transmission of respiratory viruses are poorly characterized. We analyzed the contribution of type I and type III interferon (IFN) using a mouse model in which the virus is selectively administered to the upper airways, mimicking a natural respiratory virus infection. Mice lacking functional IFN-λ receptors (Ifnlr1−/−) no longer restricted virus dissemination from the upper airways to the lungs. Ifnlr1−/− mice shed significantly more infectious virus particles via the nostrils and transmitted the virus much more efficiently to naïve contacts compared with wild-type mice or mice lacking functional type I IFN receptors. Prophylactic treatment with IFN-α or IFN-λ inhibited initial virus replication in all parts of the respiratory tract, but only IFN-λ conferred long-lasting antiviral protection in the upper airways and blocked virus transmission. Thus, IFN-λ has a decisive and non-redundant function in the upper airways that greatly limits transmission of respiratory viruses to naïve contacts. PMID:29651984

A Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP.

PubMed

Spanò, Stefania; Gao, Xiang; Hannemann, Sebastian; Lara-Tejero, María; Galán, Jorge E

2016-02-10

Cell-autonomous defense mechanisms are potent strategies that protect individual cells against intracellular pathogens. The Rab-family GTPase Rab32 was previously shown to restrict the intracellular human pathogen Salmonella Typhi, but its potential broader role in antimicrobial defense remains unknown. We show that Rab32 represents a general cell-autonomous, antimicrobial defense that is counteracted by two Salmonella effectors. Mice lacking Rab-32 or its nucleotide exchange factor BLOC-3 are permissive to S. Typhi infection and exhibit increased susceptibility to S. Typhimurium. S. Typhimurium counters this defense pathway by delivering two type III secretion effectors, SopD2, a Rab32 GAP, and GtgE, a specific Rab32 protease. An S. Typhimurium mutant strain lacking these two effectors exhibits markedly reduced virulence, which is fully restored in BLOC-3-deficient mice. These results demonstrate that a cell-autonomous, Rab32-dependent host defense pathway plays a central role in the defense against vacuolar pathogens and describe a mechanism evolved by a bacterial pathogen to counter it. Copyright © 2016 Elsevier Inc. All rights reserved.

Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants

PubMed Central

Greenwood, Edward JD; Matheson, Nicholas J; Wals, Kim; van den Boomen, Dick JH; Antrobus, Robin; Williamson, James C; Lehner, Paul J

2016-01-01

Viruses manipulate host factors to enhance their replication and evade cellular restriction. We used multiplex tandem mass tag (TMT)-based whole cell proteomics to perform a comprehensive time course analysis of >6500 viral and cellular proteins during HIV infection. To enable specific functional predictions, we categorized cellular proteins regulated by HIV according to their patterns of temporal expression. We focussed on proteins depleted with similar kinetics to APOBEC3C, and found the viral accessory protein Vif to be necessary and sufficient for CUL5-dependent proteasomal degradation of all members of the B56 family of regulatory subunits of the key cellular phosphatase PP2A (PPP2R5A-E). Quantitative phosphoproteomic analysis of HIV-infected cells confirmed Vif-dependent hyperphosphorylation of >200 cellular proteins, particularly substrates of the aurora kinases. The ability of Vif to target PPP2R5 subunits is found in primate and non-primate lentiviral lineages, and remodeling of the cellular phosphoproteome is therefore a second ancient and conserved Vif function. DOI: http://dx.doi.org/10.7554/eLife.18296.001 PMID:27690223

Global phylogeographic limits of Hawaii's avian malaria

USGS Publications Warehouse

Beadell, J.S.; Ishtiaq, F.; Covas, R.; Melo, M.; Warren, B.H.; Atkinson, C.T.; Bensch, S.; Graves, G.R.; Jhala, Y.V.; Peirce, M.A.; Rahmani, A.R.; Fonseca, D.M.; Fleischer, R.C.

2006-01-01

The introduction of avian malaria (Plasmodium relictum) to Hawaii has provided a model system for studying the influence of exotic disease on naive host populations. Little is known, however, about the origin or the genetic variation of Hawaii's malaria and traditional classification methods have confounded attempts to place the parasite within a global ecological and evolutionary context. Using fragments of the parasite mitochondrial gene cytochrome b and the nuclear gene dihydrofolate reductase-thymidylate synthase obtained from a global survey of greater than 13 000 avian samples, we show that Hawaii's avian malaria, which can cause high mortality and is a major limiting factor for many species of native passerines, represents just one of the numerous lineages composing the morphological parasite species. The single parasite lineage detected in Hawaii exhibits a broad host distribution worldwide and is dominant on several other remote oceanic islands, including Bermuda and Moorea, French Polynesia. The rarity of this lineage in the continental New World and the restriction of closely related lineages to the Old World suggest limitations to the transmission of reproductively isolated parasite groups within the morphological species. ?? 2006 The Royal Society.

Origins of HIV and the AIDS Pandemic

PubMed Central

Sharp, Paul M.; Hahn, Beatrice H.

2011-01-01

Acquired immunodeficiency syndrome (AIDS) of humans is caused by two lentiviruses, human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2). Here, we describe the origins and evolution of these viruses, and the circumstances that led to the AIDS pandemic. Both HIVs are the result of multiple cross-species transmissions of simian immunodeficiency viruses (SIVs) naturally infecting African primates. Most of these transfers resulted in viruses that spread in humans to only a limited extent. However, one transmission event, involving SIVcpz from chimpanzees in southeastern Cameroon, gave rise to HIV-1 group M—the principal cause of the AIDS pandemic. We discuss how host restriction factors have shaped the emergence of new SIV zoonoses by imposing adaptive hurdles to cross-species transmission and/or secondary spread. We also show that AIDS has likely afflicted chimpanzees long before the emergence of HIV. Tracing the genetic changes that occurred as SIVs crossed from monkeys to apes and from apes to humans provides a new framework to examine the requirements of successful host switches and to gauge future zoonotic risk. PMID:22229120

Human-Specific Bacterial Pore-Forming Toxins Induce Programmed Necrosis in Erythrocytes

PubMed Central

LaRocca, Timothy J.; Stivison, Elizabeth A.; Hod, Eldad A.; Spitalnik, Steven L.; Cowan, Peter J.; Randis, Tara M.

2014-01-01

ABSTRACT A subgroup of the cholesterol-dependent cytolysin (CDC) family of pore-forming toxins (PFTs) has an unusually narrow host range due to a requirement for binding to human CD59 (hCD59), a glycosylphosphatidylinositol (GPI)-linked complement regulatory molecule. hCD59-specific CDCs are produced by several organisms that inhabit human mucosal surfaces and can act as pathogens, including Gardnerella vaginalis and Streptococcus intermedius. The consequences and potential selective advantages of such PFT host limitation have remained unknown. Here, we demonstrate that, in addition to species restriction, PFT ligation of hCD59 triggers a previously unrecognized pathway for programmed necrosis in primary erythrocytes (red blood cells [RBCs]) from humans and transgenic mice expressing hCD59. Because they lack nuclei and mitochondria, RBCs have typically been thought to possess limited capacity to undergo programmed cell death. RBC programmed necrosis shares key molecular factors with nucleated cell necroptosis, including dependence on Fas/FasL signaling and RIP1 phosphorylation, necrosome assembly, and restriction by caspase-8. Death due to programmed necrosis in RBCs is executed by acid sphingomyelinase-dependent ceramide formation, NADPH oxidase- and iron-dependent reactive oxygen species formation, and glycolytic formation of advanced glycation end products. Bacterial PFTs that are hCD59 independent do not induce RBC programmed necrosis. RBC programmed necrosis is biochemically distinct from eryptosis, the only other known programmed cell death pathway in mature RBCs. Importantly, RBC programmed necrosis enhances the growth of PFT-producing pathogens during exposure to primary RBCs, consistent with a role for such signaling in microbial growth and pathogenesis. PMID:25161188

Structural basis of lentiviral subversion of a cellular protein degradation pathway

NASA Astrophysics Data System (ADS)

Schwefel, David; Groom, Harriet C. T.; Boucherit, Virginie C.; Christodoulou, Evangelos; Walker, Philip A.; Stoye, Jonathan P.; Bishop, Kate N.; Taylor, Ian A.

2014-01-01

Lentiviruses contain accessory genes that have evolved to counteract the effects of host cellular defence proteins that inhibit productive infection. One such restriction factor, SAMHD1, inhibits human immunodeficiency virus (HIV)-1 infection of myeloid-lineage cells as well as resting CD4+ T cells by reducing the cellular deoxynucleoside 5'-triphosphate (dNTP) concentration to a level at which the viral reverse transcriptase cannot function. In other lentiviruses, including HIV-2 and related simian immunodeficiency viruses (SIVs), SAMHD1 restriction is overcome by the action of viral accessory protein x (Vpx) or the related viral protein r (Vpr) that target and recruit SAMHD1 for proteasomal degradation. The molecular mechanism by which these viral proteins are able to usurp the host cell's ubiquitination machinery to destroy the cell's protection against these viruses has not been defined. Here we present the crystal structure of a ternary complex of Vpx with the human E3 ligase substrate adaptor DCAF1 and the carboxy-terminal region of human SAMHD1. Vpx is made up of a three-helical bundle stabilized by a zinc finger motif, and wraps tightly around the disc-shaped DCAF1 molecule to present a new molecular surface. This adapted surface is then able to recruit SAMHD1 via its C terminus, making it a competent substrate for the E3 ligase to mark for proteasomal degradation. The structure reported here provides a molecular description of how a lentiviral accessory protein is able to subvert the cell's normal protein degradation pathway to inactivate the cellular viral defence system.

The Host Range of Gammaretroviruses and Gammaretroviral Vectors Includes Post-Mitotic Neural Cells

PubMed Central

Liu, Xiu-Huai; Xu, Wenqin; Russ, Jill; Eiden, Lee E.; Eiden, Maribeth V.

2011-01-01

Background Gammaretroviruses and gammaretroviral vectors, in contrast to lentiviruses and lentiviral vectors, are reported to be restricted in their ability to infect growth-arrested cells. The block to this restriction has never been clearly defined. The original assessment of the inability of gammaretroviruses and gammaretroviral vectors to infect growth-arrested cells was carried out using established cell lines that had been growth-arrested by chemical means, and has been generalized to neurons, which are post-mitotic. We re-examined the capability of gammaretroviruses and their derived vectors to efficiently infect terminally differentiated neuroendocrine cells and primary cortical neurons, a target of both experimental and therapeutic interest. Methodology/Principal Findings Using GFP expression as a marker for infection, we determined that both growth-arrested (NGF-differentiated) rat pheochromocytoma cells (PC12 cells) and primary rat cortical neurons could be efficiently transduced, and maintained long-term protein expression, after exposure to murine leukemia virus (MLV) and MLV-based retroviral vectors. Terminally differentiated PC12 cells transduced with a gammaretroviral vector encoding the anti-apoptotic protein Bcl-xL were protected from cell death induced by withdrawal of nerve growth factor (NGF), demonstrating gammaretroviral vector-mediated delivery and expression of genes at levels sufficient for therapeutic effect in non-dividing cells. Post-mitotic rat cortical neurons were also shown to be susceptible to transduction by murine replication-competent gammaretroviruses and gammaretroviral vectors. Conclusions/Significance These findings suggest that the host range of gammaretroviruses includes post-mitotic and other growth-arrested cells in mammals, and have implications for re-direction of gammaretroviral gene therapy to neurological disease. PMID:21464894

Retroviral restriction and dependency factors in primates and carnivores

PubMed Central

Fadel, Hind J.; Poeschla, Eric M.

2014-01-01

Recent studies have extended the rapidly developing retroviral restriction factor field to cells of carnivore species. Carnivoran genomes, and the domestic cat genome in particular, are revealing intriguing properties vis-à;-vis the primate and feline lentiviruses, not only with respect to their repertoires of virus-blocking restriction factors but also replication-enabling dependency factors. Therapeutic application of restriction factors is envisioned for human immunodeficiency virus (HIV) disease and the feline immunodeficiency virus (FIV) model has promise for testing important hypotheses at the basic and translational level. Feline cell-tropic HIV-1 clones have also been generated by a strategy of restriction factor evasion. We review progress in this area in the context of what is known about retroviral restriction factors such as TRIM5alpha, TRIMCyp, APOBEC3 proteins and BST-2/Tetherin. PMID:21715018

Spatial Variation and Survival of Salmonella enterica Subspecies in a Population of Australian Sleepy Lizards (Tiliqua rugosa).

PubMed

Parsons, Sandra K; Bull, C Michael; Gordon, David M

2015-09-01

The life cycles of many enteric bacterial species require a transition between two very distinct environments. Their primary habitat is the gastrointestinal tract of the host, while their secondary habitat, during transmission from one host to another, consists of environments external to the host, such as soil, water, and sediments. Consequently, both host and environmental factors shape the genetic structure of enteric bacterial populations. This study examined the distribution of four Salmonella enterica subspecies in a population of sleepy lizards, Tiliqua rugosa, in a semiarid region of South Australia. The lizards living within the 1,920-m by 720-m study site were radio tracked, and their enteric bacteria were sampled at regular intervals throughout their active seasons in the years 2001, 2002, and 2006. Four of the six subspecies of S. enterica were present in this population and were nonrandomly distributed among the lizards. In particular, S. enterica subsp. diarizonae was restricted to lizards living in the most shaded parts of the study site with an overstorey of Casuarina trees. Experiments undertaken to investigate the survival of S. enterica cells under seminatural conditions revealed that cell survival decreased with increased exposure to elevated temperatures and UV light. Among the three S. enterica subspecies tested, S. enterica subsp. diarizonae consistently had an average expected life span that was shorter than that observed for the other two subspecies. There was no indication in the data that there was any competitive dominance hierarchy among the S. enterica subspecies within individual hosts. Thus, the nonrandom distribution of S. enterica subspecies in this population of lizards appears to be driven by their different survival characteristics in the external environment. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Limited by the host: Host age hampers establishment of holoparasite Cuscuta epithymum

NASA Astrophysics Data System (ADS)

Meulebrouck, Klaar; Verheyen, Kris; Brys, Rein; Hermy, Martin

2009-07-01

A good understanding of the relationship between plant establishment and the ecosystem of which they are part of is needed to conserve rare plant species. Introduction experiments offer a direct test of recruitment limitation, but generally only the seed germination and seedling phases are monitored. Thus the relative importance of different establishment stages in the process of recruitment is not considered. This is particularly true for parasitic plants where empirical data are generally missing. During two consecutive growing seasons we examined the effect of heathland management applications, degree of heathland succession (pioneer, building and mature phase) and seed-density on the recruitment and establishment of the endangered holoparasite Cuscuta epithymum. In general, recruitment after two growing seasons was low with 4.79% of the sown seeds that successfully emerged to the seedling stage and a final establishment of 89 flowering adults (i.e. <1.5% of the sown seeds). Although a higher seed-density resulted in a higher number of seedlings, seed-density did not significantly affected relative germination percentages. The management type and subsequent heath succession had no significant effect on seedling emergence; whereas, seedling attachment to the host, establishment and growth to full-grown size were hampered in older heath vegetation (i.e. high, dense, and mature canopy). Establishment was most successful in turf-cut pioneer heathland, characterised by a relatively open and low vegetation of young Calluna vulgaris. The age of C. vulgaris, C. epithymum's main host, proved to be the most limiting factor. These results emphasise the importance of site quality (i.e. successional phase of its host) on recruitment success of C. epithymum, which is directly affected by the management applied to the vegetation. Lack of any heathland management will thus seriously restrict establishment of the endangered parasite.

Mycobacterium avium subspecies paratuberculosis isolates from sheep and goats show reduced persistence in bovine macrophages than cattle, bison, deer and wild boar strains regardless of genotype.

PubMed

Abendaño, Naiara; Sevilla, Iker A; Prieto, José Miguel; Garrido, Joseba M; Juste, Ramon A; Alonso-Hearn, Marta

2013-05-03

Assessment of the virulence of isolates of Mycobacterium avium subsp. paratuberculosis (Map) exhibiting distinct genotypes and isolated from different hosts may help to clarify the degree to which clinical manifestations of the disease in cattle can be attributed to bacterial or to host factors. The objective of this study was to test the ability of 10 isolates of Map representing distinct genotypes and isolated from domestic (cattle, sheep, and goat), and wildlife animal species (fallow deer, deer, wild boar, and bison) to enter and grow in bovine macrophages. The isolates were previously typed using IS1311 PCR followed by restriction endonuclease analysis into types C, S or B. Intracellular growth of the isolates in a bovine macrophage-like cell line (BoMac) and in primary bovine monocyte-derived macrophages (MDM) was evaluated by quantification of CFU numbers in the initial inoculum and inside of the host cells at 2h and 7 d p.i. using an automatic liquid culture system (Bactec MGIT 960). Individual data illustrated that growth was less variable in BoMac than in MDM cells. All the isolates from goat and sheep hosts persisted within BoMac cells in lower CFU numbers than the other tested isolates after 7 days of infection regardless of genotype. In addition, BoMac cells exhibited differential inflammatory, apoptotic and destructive responses when infected with a bovine or an ovine isolate; which correlated with the differential survival of these strains within BoMac cells. Our results indicated that the survival of the tested Map isolates within bovine macrophages is associated with the specific host from which the isolates were initially isolated. Copyright © 2013 Elsevier B.V. All rights reserved.

Explaining the host-finding behavior of blood-sucking insects: computerized simulation of the effects of habitat geometry on tsetse fly movement.

PubMed

Vale, Glyn A; Hargrove, John W; Solano, Philippe; Courtin, Fabrice; Rayaisse, Jean-Baptiste; Lehane, Michael J; Esterhuizen, Johan; Tirados, Inaki; Torr, Stephen J

2014-06-01

Male and female tsetse flies feed exclusively on vertebrate blood. While doing so they can transmit the diseases of sleeping sickness in humans and nagana in domestic stock. Knowledge of the host-orientated behavior of tsetse is important in designing bait methods of sampling and controlling the flies, and in understanding the epidemiology of the diseases. For this we must explain several puzzling distinctions in the behavior of the different sexes and species of tsetse. For example, why is it that the species occupying savannahs, unlike those of riverine habitats, appear strongly responsive to odor, rely mainly on large hosts, are repelled by humans, and are often shy of alighting on baits? A deterministic model that simulated fly mobility and host-finding success suggested that the behavioral distinctions between riverine, savannah and forest tsetse are due largely to habitat size and shape, and the extent to which dense bushes limit occupiable space within the habitats. These factors seemed effective primarily because they affect the daily displacement of tsetse, reducing it by up to ∼70%. Sex differences in behavior are explicable by females being larger and more mobile than males. Habitat geometry and fly size provide a framework that can unify much of the behavior of all sexes and species of tsetse everywhere. The general expectation is that relatively immobile insects in restricted habitats tend to be less responsive to host odors and more catholic in their diet. This has profound implications for the optimization of bait technology for tsetse, mosquitoes, black flies and tabanids, and for the epidemiology of the diseases they transmit.

Spatial Variation and Survival of Salmonella enterica Subspecies in a Population of Australian Sleepy Lizards (Tiliqua rugosa)

PubMed Central

Parsons, Sandra K.; Bull, C. Michael

2015-01-01

The life cycles of many enteric bacterial species require a transition between two very distinct environments. Their primary habitat is the gastrointestinal tract of the host, while their secondary habitat, during transmission from one host to another, consists of environments external to the host, such as soil, water, and sediments. Consequently, both host and environmental factors shape the genetic structure of enteric bacterial populations. This study examined the distribution of four Salmonella enterica subspecies in a population of sleepy lizards, Tiliqua rugosa, in a semiarid region of South Australia. The lizards living within the 1,920-m by 720-m study site were radio tracked, and their enteric bacteria were sampled at regular intervals throughout their active seasons in the years 2001, 2002, and 2006. Four of the six subspecies of S. enterica were present in this population and were nonrandomly distributed among the lizards. In particular, S. enterica subsp. diarizonae was restricted to lizards living in the most shaded parts of the study site with an overstorey of Casuarina trees. Experiments undertaken to investigate the survival of S. enterica cells under seminatural conditions revealed that cell survival decreased with increased exposure to elevated temperatures and UV light. Among the three S. enterica subspecies tested, S. enterica subsp. diarizonae consistently had an average expected life span that was shorter than that observed for the other two subspecies. There was no indication in the data that there was any competitive dominance hierarchy among the S. enterica subspecies within individual hosts. Thus, the nonrandom distribution of S. enterica subspecies in this population of lizards appears to be driven by their different survival characteristics in the external environment. PMID:26092451

Sequential cloning of chromosomes

DOEpatents

Lacks, S.A.

1995-07-18

A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes. 9 figs.

Global genomics and proteomics approaches to identify host factors as targets to induce resistance against Tomato bushy stunt virus.

PubMed

Nagy, Peter D; Pogany, Judit

2010-01-01

The success of RNA viruses as pathogens of plants, animals, and humans depends on their ability to reprogram the host cell metabolism to support the viral infection cycle and to suppress host defense mechanisms. Plus-strand (+)RNA viruses have limited coding potential necessitating that they co-opt an unknown number of host factors to facilitate their replication in host cells. Global genomics and proteomics approaches performed with Tomato bushy stunt virus (TBSV) and yeast (Saccharomyces cerevisiae) as a model host have led to the identification of 250 host factors affecting TBSV RNA replication and recombination or bound to the viral replicase, replication proteins, or the viral RNA. The roles of a dozen host factors involved in various steps of the replication process have been validated in yeast as well as a plant host. Altogether, the large number of host factors identified and the great variety of cellular functions performed by these factors indicate the existence of a truly complex interaction between TBSV and the host cell. This review summarizes the advantages of using a simple plant virus and yeast as a model host to advance our understanding of virus-host interactions at the molecular and cellular levels. The knowledge of host factors gained can potentially be used to inhibit virus replication via gene silencing, expression of dominant negative mutants, or design of specific chemical inhibitors leading to novel specific or broad-range resistance and antiviral tools against (+)RNA plant viruses. Copyright © 2010 Elsevier Inc. All rights reserved.

Does sex-biased dispersal account for the lack of geographic and host-associated differentiation in introduced populations of an aphid parasitoid?

PubMed Central

Zepeda-Paulo, Francisca; Lavandero, Blas; Mahéo, Frédérique; Dion, Emilie; Outreman, Yannick; Simon, Jean-Christophe; Figueroa, Christian C

2015-01-01

Host recognition and use in female parasitoids strongly relies on host fidelity, a plastic behavior which can significantly restrict the host preferences of parasitoids, thus reducing the gene flow between parasitoid populations attacking different insect hosts. However, the effect of migrant males on the genetic differentiation of populations has been frequently ignored in parasitoids, despite its known impact on gene flow between populations. Hence, we studied the extent of gene flow mediated by female and male parasitoids by assessing sibship relationships among parasitoids within and between populations, and its impact on geographic and host-associated differentiation in the aphid parasitoid Aphidius ervi. We report evidences of a high gene flow among parasitoid populations on different aphid hosts and geographic locations. The high gene flow among parasitoid populations was found to be largely male mediated, suggested by significant differences in the distribution of full-sib and paternal half-sib dyads of parasitoid populations. PMID:26078852

Dynamic Modulation of Expression of Lentiviral Restriction Factors in Primary CD4+ T Cells following Simian Immunodeficiency Virus Infection.

PubMed

Rahmberg, Andrew R; Rajakumar, Premeela A; Billingsley, James M; Johnson, R Paul

2017-04-01

Although multiple restriction factors have been shown to inhibit HIV/SIV replication, little is known about their expression in vivo Expression of 45 confirmed and putative HIV/SIV restriction factors was analyzed in CD4 + T cells from peripheral blood and the jejunum in rhesus macaques, revealing distinct expression patterns in naive and memory subsets. In both peripheral blood and the jejunum, memory CD4 + T cells expressed higher levels of multiple restriction factors compared to naive cells. However, relative to their expression in peripheral blood CD4 + T cells, jejunal CCR5 + CD4 + T cells exhibited significantly lower expression of multiple restriction factors, including APOBEC3G , MX2 , and TRIM25 , which may contribute to the exquisite susceptibility of these cells to SIV infection. In vitro stimulation with anti-CD3/CD28 antibodies or type I interferon resulted in upregulation of distinct subsets of multiple restriction factors. After infection of rhesus macaques with SIVmac239, the expression of most confirmed and putative restriction factors substantially increased in all CD4 + T cell memory subsets at the peak of acute infection. Jejunal CCR5 + CD4 + T cells exhibited the highest levels of SIV RNA, corresponding to the lower restriction factor expression in this subset relative to peripheral blood prior to infection. These results illustrate the dynamic modulation of confirmed and putative restriction factor expression by memory differentiation, stimulation, tissue microenvironment and SIV infection and suggest that differential expression of restriction factors may play a key role in modulating the susceptibility of different populations of CD4 + T cells to lentiviral infection. IMPORTANCE Restriction factors are genes that have evolved to provide intrinsic defense against viruses. HIV and simian immunodeficiency virus (SIV) target CD4 + T cells. The baseline level of expression in vivo and degree to which expression of restriction factors is modulated by conditions such as CD4 + T cell differentiation, stimulation, tissue location, or SIV infection are currently poorly understood. We measured the expression of 45 confirmed and putative restriction factors in primary CD4 + T cells from rhesus macaques under various conditions, finding dynamic changes in each state. Most dramatically, in acute SIV infection, the expression of almost all target genes analyzed increased. These are the first measurements of many of these confirmed and putative restriction factors in primary cells or during the early events after SIV infection and suggest that the level of expression of restriction factors may contribute to the differential susceptibility of CD4 + T cells to SIV infection. Copyright © 2017 American Society for Microbiology.

A Mechanism to Avoid Collusion Attacks Based on Code Passing in Mobile Agent Systems

NASA Astrophysics Data System (ADS)

Jaimez, Marc; Esparza, Oscar; Muñoz, Jose L.; Alins-Delgado, Juan J.; Mata-Díaz, Jorge

Mobile agents are software entities consisting of code, data, state and itinerary that can migrate autonomously from host to host executing their code. Despite its benefits, security issues strongly restrict the use of code mobility. The protection of mobile agents against the attacks of malicious hosts is considered the most difficult security problem to solve in mobile agent systems. In particular, collusion attacks have been barely studied in the literature. This paper presents a mechanism that avoids collusion attacks based on code passing. Our proposal is based on a Multi-Code agent, which contains a different variant of the code for each host. A Trusted Third Party is responsible for providing the information to extract its own variant to the hosts, and for taking trusted timestamps that will be used to verify time coherence.

Archaeal Extrachromosomal Genetic Elements

PubMed Central

Wang, Haina; Peng, Nan; Shah, Shiraz A.

2015-01-01

SUMMARY Research on archaeal extrachromosomal genetic elements (ECEs) has progressed rapidly in the past decade. To date, over 60 archaeal viruses and 60 plasmids have been isolated. These archaeal viruses exhibit an exceptional diversity in morphology, with a wide array of shapes, such as spindles, rods, filaments, spheres, head-tails, bottles, and droplets, and some of these new viruses have been classified into one order, 10 families, and 16 genera. Investigation of model archaeal viruses has yielded important insights into mechanisms underlining various steps in the viral life cycle, including infection, DNA replication and transcription, and virion egression. Many of these mechanisms are unprecedented for any known bacterial or eukaryal viruses. Studies of plasmids isolated from different archaeal hosts have also revealed a striking diversity in gene content and innovation in replication strategies. Highly divergent replication proteins are identified in both viral and plasmid genomes. Genomic studies of archaeal ECEs have revealed a modular sequence structure in which modules of DNA sequence are exchangeable within, as well as among, plasmid families and probably also between viruses and plasmids. In particular, it has been suggested that ECE-host interactions have shaped the coevolution of ECEs and their archaeal hosts. Furthermore, archaeal hosts have developed defense systems, including the innate restriction-modification (R-M) system and the adaptive CRISPR (clustered regularly interspaced short palindromic repeats) system, to restrict invasive plasmids and viruses. Together, these interactions permit a delicate balance between ECEs and their hosts, which is vitally important for maintaining an innovative gene reservoir carried by ECEs. In conclusion, while research on archaeal ECEs has just started to unravel the molecular biology of these genetic entities and their interactions with archaeal hosts, it is expected to accelerate in the next decade. PMID:25694123

Mechanisms of inflammation-driven bacterial dysbiosis in the gut

PubMed Central

Zeng, MY; Inohara, N; Nuñez, G

2018-01-01

The gut microbiota has diverse and essential roles in host metabolism, development of the immune system and as resistance to pathogen colonization. Perturbations of the gut microbiota, termed gut dysbiosis, are commonly observed in diseases involving inflammation in the gut, including inflammatory bowel disease, infection, colorectal cancer and food allergies. Importantly, the inflamed microenvironment in the gut is particularly conducive to blooms of Enterobacteriaceae, which acquire fitness benefits while other families of symbiotic bacteria succumb to environmental changes inflicted by inflammation. Here we summarize studies that examined factors in the inflamed gut that contribute to blooms of Enterobacterieaceae, and highlight potential approaches to restrict Enterobacterial blooms in treating diseases that are otherwise complicated by overgrowth of virulent Enterobacterial species in the gut. PMID:27554295

Equine Myxovirus Resistance Protein 2 Restricts Lentiviral Replication by Blocking Nuclear Uptake of Capsid Protein.

PubMed

Ji, Shuang; Na, Lei; Ren, Huiling; Wang, Yujie; Wang, Xiaojun

2018-05-09

Human Myxovirus resistance 2 (huMxB) has been shown to be a determinant type I interferon-induced host factor involved in the inhibition of HIV-1 as well as many other primate lentiviruses. This blocking occurs after the reverse transcription of viral RNA and ahead of the integration into the host DNA, which is closely connected to the ability of the protein to bind the viral capsid. To date, Mx2s derived from non-primate animals have shown no capacity for HIV-1 suppression. In this study, we examined the restrictive effect of equine Mx2 (eqMx2) on both the equine infectious anemia virus (EIAV) and HIV-1 and investigated possible mechanisms for its specific function. We demonstrated that IFNα/β upregulates the expression of eqMx2 in equine monocyte-derived macrophages (eMDMs). Overexpression of eqMx2 significantly suppresses the replication of EIAV, HIV-1, and SIVs, but not that of MLV. Knockdown of eqMx2 transcription weakens the inhibition of EIAV replication by type I interferon. Interestingly, immunofluorescence assays suggest that the subcellular localization of eqMx2 changes following virus infection, from being dispersed in the cytoplasm to being accumulated at the nuclear envelope. Furthermore, eqMx2 blocks the nuclear uptake of the proviral genome by binding to the viral capsid. The N-truncated mutant of eqMx2 lost the ability to bind the viral capsid as well as the restriction effect for lentiviruses. These results improve our understanding of the Mx2 protein in non-primate animals. IMPORTANCE Previous research has shown that the antiviral ability of Mx2s is confined to primates, particularly humans. EIAV has been shown to be insensitive to the restriction by human MxB. Here, we described the function of equine Mx2. This protein plays an important role in the suppression of EIAV, HIV-1, and SIVs. The antiviral activity of eqMx2 depends on its subcellular location as well as its capsid binding capacity. Our results showed that following viral infection, eqMx2 changes its original cytoplasmic location and accumulates at the nuclear envelope where it binds to the viral capsid and blocks the nuclear entry of reverse transcribed proviral DNAs. In contrast, huMxB does not bind to the EIAV capsid and shows no EIAV restriction effect. These studies expand our understanding of the function of the equine Mx2 protein. Copyright © 2018 Ji et al.

Lentiviral infection of proliferating brain macrophages in HIV and simian immunodeficiency virus encephalitis despite sterile alpha motif and histidine-aspartate domain-containing protein 1 expression

PubMed Central

Lindgren, Allison A.; Filipowicz, Adam R.; Hattler, Julian B.; Kim, Soon Ok; Chung, Hye Kyung; Kuroda, Marcelo J.; Johnson, Edward M.; Kim, Woong-Ki

2018-01-01

Objective: HIV-1 infection of the brain and related cognitive impairment remain prevalent in HIV-1-infected individuals despite combination antiretroviral therapy. Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) is a newly identified host restriction factor that blocks the replication of HIV-1 and other retroviruses in myeloid cells. Cell cycle-regulated phosphorylation at residue Thr592 and viral protein X (Vpx)-mediated degradation of SAMHD1 have been shown to bypass SAMHD1 restriction in vitro. Herein, we investigated expression and phosphorylation of SAMHD1 in vivo in relation to macrophage infection and proliferation during the neuropathogenesis of HIV-1 and simian immunodeficiency virus (SIV) encephalitis. Methods: Using brain and other tissues from uninfected and SIV-infected macaques with or without encephalitis, we performed immunohistochemistry, multilabel fluorescence microscopy and western blot to examine the expression, localization and phosphorylation of SAMHD1. Results: The number of SAMHD1+ nuclei increased in encephalitic brains despite the presence of Vpx. Many of these cells were perivascular macrophages, although subsets of SAMHD1+ microglia and endothelial cells were also observed. The SAMHD1+ macrophages were shown to be both infected and proliferating. Moreover, the presence of cycling SAMHD1+ brain macrophages was confirmed in the tissue of HIV-1-infected patients with encephalitis. Finally, western blot analysis of brain-protein extracts from SIV-infected macaques showed that SAMHD1 protein exists in the brain mainly as an inactive Thr592-phosphorylated form. Conclusion: The ability of SAMHD1 to act as a restriction factor for SIV/HIV in the brain is likely bypassed in proliferating brain macrophages through the phosphorylation-mediated inactivation, not Vpx-mediated degradation of SAMHD1. PMID:29698322

Influenza A virus-induced degradation of eukaryotic translation initiation factor 4B contributes to viral replication by suppressing IFITM3 protein expression.

PubMed

Wang, Song; Chi, Xiaojuan; Wei, Haitao; Chen, Yuhai; Chen, Zhilong; Huang, Shile; Chen, Ji-Long

2014-08-01

Although alteration in host cellular translation machinery occurs in virus-infected cells, the role of such alteration and the precise pathogenic processes are not well understood. Influenza A virus (IAV) infection shuts off host cell gene expression at transcriptional and translational levels. Here, we found that the protein level of eukaryotic translation initiation factor 4B (eIF4B), an integral component of the translation initiation apparatus, was dramatically reduced in A549 cells as well as in the lung, spleen, and thymus of mice infected with IAV. The decrease in eIF4B level was attributed to lysosomal degradation of eIF4B, which was induced by viral NS1 protein. Silencing eIF4B expression in A549 cells significantly promoted IAV replication, and conversely, overexpression of eIF4B markedly inhibited the viral replication. Importantly, we observed that eIF4B knockdown transgenic mice were more susceptible to IAV infection, exhibiting faster weight loss, shorter survival time, and more-severe organ damage. Furthermore, we demonstrated that eIF4B regulated the expression of interferon-induced transmembrane protein 3 (IFITM3), a critical protein involved in immune defense against a variety of RNA viruses, including influenza virus. Taken together, our findings reveal that eIF4B plays an important role in host defense against IAV infection at least by regulating the expression of IFITM3, which restricts viral entry and thereby blocks early stages of viral production. These data also indicate that influenza virus has evolved a strategy to overcome host innate immunity by downregulating eIF4B protein. Influenza A virus (IAV) infection stimulates the host innate immune system, in part, by inducing interferons (IFNs). Secreted IFNs activate the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, leading to elevated transcription of a large group of IFN-stimulated genes that have antiviral function. To circumvent the host innate immune response, influenza virus has evolved multiple strategies for suppressing the production of IFNs. Here, we show that IAV infection induces lysosomal degradation of eIF4B protein; and eIF4B inhibits IAV replication by upregulating expression of interferon-induced transmembrane protein 3 (IFITM3), a key protein that protects the host from virus infection. Our finding illustrates a critical role of eIF4B in the host innate immune response and provides novel insights into the complex mechanisms by which influenza virus interacts with its host. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Advanced sclerosis of the chest wall skin secondary to chronic graft-versus-host disease: a case with severe restrictive lung defect.

PubMed

Ödek, Çağlar; Kendirli, Tanil; İleri, Talia; Yaman, Ayhan; Fatih Çakmakli, Hasan; Ince, Elif; İnce, Erdal; Ertem, Mehmet

2014-10-01

Pulmonary chronic graft-versus-host disease (cGvHD) is one of the most common causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (aHSCT). Herein, we describe a patient with severe restrictive lung defect secondary to cGvHD. A 21-year-old male patient was admitted to our pediatric intensive care unit (PICU) with pneumonia and respiratory distress. He had a history of aHSCT for chronic myelogeneous leukemia at the age of 17 years. Six months after undergoing aHSCT, he had developed cGvHD involving skin, mouth, eye, lung, liver, and gastrointestinal tract. At the time of PICU admission he had respiratory distress and required ventilation support. Thorax high-resolution computed tomography was consistent with bronchiolitis obliterans. Although bronchiolitis obliterans is an obstructive lung defect, a restrictive pattern became prominent in the clinical course because of the sclerotic chest wall skin. The activity of cGvHD kept increasing despite the therapy and we lost the patient because of severe respiratory distress and massive hemoptysis secondary to bronchiectasis. In conclusion, pulmonary cGvHD can present with restrictive changes related with the advanced sclerosis of the chest wall skin. Performing a fasciotomy or a scar revision for the rigid chest wall in selected patients may improve the patients ventilation.

Evolution in action: climate change, biodiversity dynamics and emerging infectious disease

PubMed Central

Hoberg, Eric P.; Brooks, Daniel R.

2015-01-01

Climatological variation and ecological perturbation have been pervasive drivers of faunal assembly, structure and diversification for parasites and pathogens through recurrent events of geographical and host colonization at varying spatial and temporal scales of Earth history. Episodic shifts in climate and environmental settings, in conjunction with ecological mechanisms and host switching, are often critical determinants of parasite diversification, a view counter to more than a century of coevolutionary thinking about the nature of complex host–parasite assemblages. Parasites are resource specialists with restricted host ranges, yet shifts onto relatively unrelated hosts are common during phylogenetic diversification of parasite lineages and directly observable in real time. The emerging Stockholm Paradigm resolves this paradox: Ecological Fitting (EF)—phenotypic flexibility and phylogenetic conservatism in traits related to resource use, most notably host preference—provides many opportunities for rapid host switching in changing environments, without the evolution of novel host-utilization capabilities. Host shifts via EF fuel the expansion phase of the Oscillation Hypothesis of host range and speciation and, more generally, the generation of novel combinations of interacting species within the Geographic Mosaic Theory of Coevolution. In synergy, an environmental dynamic of Taxon Pulses establishes an episodic context for host and geographical colonization. PMID:25688014

A review of the epidemiological and clinical aspects of West Nile virus.

PubMed

Gray, Timothy J; Webb, Cameron E

2014-01-01

The resurgence of West Nile virus (WNV) in North America and Europe in recent years has raised the concerns of local authorities and highlighted that mosquito-borne disease is not restricted to tropical regions of the world. WNV is maintained in enzootic cycles involving, primarily, Culex spp. mosquitoes and avian hosts, with epizootic spread to mammals, including horses and humans. Human infection results in symptomatic illness in approximately one-fifth of cases and neuroinvasive disease in less than 1% of infected persons. The most consistently recognized risk factor for neuroinvasive disease is older age, although diabetes mellitus, alcohol excess, and a history of cancer may also increase risk. Despite the increasing public health concern, the current WNV treatments are inadequate. Current evidence supporting the use of ribavirin, interferon α, and WNV-specific immunoglobulin are reviewed. Nucleic acid detection has been an important diagnostic development, which is particularly important for the protection of the donated blood supply. While effective WNV vaccines are widely available for horses, no human vaccine has been registered. Uncertainty surrounds the magnitude of future risk posed by WNV, and predictive models are limited by the heterogeneity of environmental, vector, and host factors, even in neighboring regions. However, recent history has demonstrated that for regions where suitable mosquito vectors and reservoir hosts are present, there will be a risk of major epidemics. Given the potential for these outbreaks to include severe neuroinvasive disease, strategies should be implemented to monitor for, and respond to, outbreak risk. While broadscale mosquito control programs will assist in reducing the abundance of mosquito populations and subsequently reduce the risks of disease, for many individuals, the use of topical insect repellents and other personal protective strategies will remain the first line of defense against infection.

A review of the epidemiological and clinical aspects of West Nile virus

PubMed Central

Gray, Timothy J; Webb, Cameron E

2014-01-01

The resurgence of West Nile virus (WNV) in North America and Europe in recent years has raised the concerns of local authorities and highlighted that mosquito-borne disease is not restricted to tropical regions of the world. WNV is maintained in enzootic cycles involving, primarily, Culex spp. mosquitoes and avian hosts, with epizootic spread to mammals, including horses and humans. Human infection results in symptomatic illness in approximately one-fifth of cases and neuroinvasive disease in less than 1% of infected persons. The most consistently recognized risk factor for neuroinvasive disease is older age, although diabetes mellitus, alcohol excess, and a history of cancer may also increase risk. Despite the increasing public health concern, the current WNV treatments are inadequate. Current evidence supporting the use of ribavirin, interferon α, and WNV-specific immunoglobulin are reviewed. Nucleic acid detection has been an important diagnostic development, which is particularly important for the protection of the donated blood supply. While effective WNV vaccines are widely available for horses, no human vaccine has been registered. Uncertainty surrounds the magnitude of future risk posed by WNV, and predictive models are limited by the heterogeneity of environmental, vector, and host factors, even in neighboring regions. However, recent history has demonstrated that for regions where suitable mosquito vectors and reservoir hosts are present, there will be a risk of major epidemics. Given the potential for these outbreaks to include severe neuroinvasive disease, strategies should be implemented to monitor for, and respond to, outbreak risk. While broadscale mosquito control programs will assist in reducing the abundance of mosquito populations and subsequently reduce the risks of disease, for many individuals, the use of topical insect repellents and other personal protective strategies will remain the first line of defense against infection. PMID:24748813

The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice.

PubMed

Deshmukh, Hitesh S; Liu, Yuhong; Menkiti, Ogechukwu R; Mei, Junjie; Dai, Ning; O'Leary, Claire E; Oliver, Paula M; Kolls, Jay K; Weiser, Jeffrey N; Worthen, G Scott

2014-05-01

Neonatal colonization by microbes, which begins immediately after birth, is influenced by gestational age and the mother's microbiota and is modified by exposure to antibiotics. In neonates, prolonged duration of antibiotic therapy is associated with increased risk of late-onset sepsis (LOS), a disorder controlled by neutrophils. A role for the microbiota in regulating neutrophil development and susceptibility to sepsis in the neonate remains unclear. We exposed pregnant mouse dams to antibiotics in drinking water to limit transfer of maternal microbes to the neonates. Antibiotic exposure of dams decreased the total number and composition of microbes in the intestine of the neonates. This was associated with decreased numbers of circulating and bone marrow neutrophils and granulocyte/macrophage-restricted progenitor cells in the bone marrow of antibiotic-treated and germ-free neonates. Antibiotic exposure of dams reduced the number of interleukin-17 (IL-17)-producing cells in the intestine and production of granulocyte colony-stimulating factor (G-CSF). Granulocytopenia was associated with impaired host defense and increased susceptibility to Escherichia coli K1 and Klebsiella pneumoniae sepsis in antibiotic-treated neonates, which could be partially reversed by administration of G-CSF. Transfer of a normal microbiota into antibiotic-treated neonates induced IL-17 production by group 3 innate lymphoid cells (ILCs) in the intestine, increasing plasma G-CSF levels and neutrophil numbers in a Toll-like receptor 4 (TLR4)- and myeloid differentiation factor 88 (MyD88)-dependent manner and restored IL-17-dependent resistance to sepsis. Specific depletion of ILCs prevented IL-17- and G-CSF-dependent granulocytosis and resistance to sepsis. These data support a role for the intestinal microbiota in regulation of granulocytosis, neutrophil homeostasis and host resistance to sepsis in neonates.

LINE-1 Retroelements Complexed and Inhibited by Activation Induced Cytidine Deaminase

PubMed Central

Metzner, Mirjam; Jäck, Hans-Martin; Wabl, Matthias

2012-01-01

LINE-1 (abbreviated L1) is a major class of retroelements in humans and mice. If unrestricted, retroelements accumulate in the cytoplasm and insert their DNA into the host genome, with the potential to cause autoimmune disease and cancer. Retroviruses and other retroelements are inhibited by proteins of the APOBEC family, of which activation-induced cytidine deaminase (AID) is a member. Although AID is mainly known for being a DNA mutator shaping the antibody repertoire in B lymphocytes, we found that AID also restricts de novo L1 integrations in B- and non-B-cell lines. It does so by decreasing the protein level of open reading frame 1 (ORF1) of both exogenous and endogenous L1. In activated B lymphocytes, AID deficiency increased L1 mRNA 1.6-fold and murine leukemia virus (MLV) mRNA 2.7-fold. In cell lines and activated B lymphocytes, AID forms cytoplasmic high-molecular-mass complexes with L1 mRNA, which may contribute to L1 restriction. Because AID-deficient activated B lymphocytes do not express ORF1 protein, we suggest that ORF1 protein expression is inhibited by additional restriction factors in these cells. The greater increase in MLV compared to L1 mRNA in AID-deficient activated B lymphocytes may indicate less strict surveillance of retrovirus. PMID:23133680

The role of BST2/tetherin in infection with the feline retroviruses

PubMed Central

Dietrich, Isabelle; Hosie, Margaret J.; Willett, Brian J.

2014-01-01

The recently identified host restriction factor tetherin (BST-2, CD317) potently inhibits the release of nascent retrovirus particles from infected cells. Recently, we reported the identification and characterization of tetherin as a novel feline retroviral restriction factor. Based on homology to human tetherin we identified a putative tetherin gene in the genome of the domestic cat (Felis catus) which was found to be expressed in different feline cell lines both prior to and post treatment with either type I or type II interferon (IFN). The predicted structure of feline tetherin (feTHN) was that of a type II single-pass transmembrane protein encoding an N-terminal transmembrane anchor, central predicted coiled-coil bearing extracellular domain to promote dimerization, and a C-terminal GPI-anchor, consistent with conservation of structure between human and feline tetherin. FeTHN displayed potent inhibition of feline immunodeficiency virus (FIV) and human immunodeficiency virus type 1 (HIV-1) particle release in single-cycle replication assays. Notably, feTHN activity was resistant to antagonism by HIV-1 Vpu. However, stable ectopic expression of feTHN mRNA in different feline cell lines had no inhibitory effect on the growth of diverse primary or cell culture-adapted strains of FIV. Hence, whereas feline tetherin efficiently blocks viral particle release in single-cycle replication assays, it might not prevent dissemination of feline retroviruses in vivo. PMID:21715020

Comparative genomic analysis of Helicobacter pylori from Malaysia identifies three distinct lineages suggestive of differential evolution.

PubMed

Kumar, Narender; Mariappan, Vanitha; Baddam, Ramani; Lankapalli, Aditya K; Shaik, Sabiha; Goh, Khean-Lee; Loke, Mun Fai; Perkins, Tim; Benghezal, Mohammed; Hasnain, Seyed E; Vadivelu, Jamuna; Marshall, Barry J; Ahmed, Niyaz

2015-01-01

The discordant prevalence of Helicobacter pylori and its related diseases, for a long time, fostered certain enigmatic situations observed in the countries of the southern world. Variation in H. pylori infection rates and disease outcomes among different populations in multi-ethnic Malaysia provides a unique opportunity to understand dynamics of host-pathogen interaction and genome evolution. In this study, we extensively analyzed and compared genomes of 27 Malaysian H. pylori isolates and identified three major phylogeographic lineages: hspEastAsia, hpEurope and hpSouthIndia. The analysis of the virulence genes within the core genome, however, revealed a comparable pathogenic potential of the strains. In addition, we identified four genes limited to strains of East-Asian lineage. Our analyses identified a few strain-specific genes encoding restriction modification systems and outlined 311 core genes possibly under differential evolutionary constraints, among the strains representing different ethnic groups. The cagA and vacA genes also showed variations in accordance with the host genetic background of the strains. Moreover, restriction modification genes were found to be significantly enriched in East-Asian strains. An understanding of these variations in the genome content would provide significant insights into various adaptive and host modulation strategies harnessed by H. pylori to effectively persist in a host-specific manner. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

The cytoskeleton in cell-autonomous immunity: structural determinants of host defence

PubMed Central

Mostowy, Serge; Shenoy, Avinash R.

2016-01-01

Host cells use antimicrobial proteins, pathogen-restrictive compartmentalization and cell death in their defence against intracellular pathogens. Recent work has revealed that four components of the cytoskeleton — actin, microtubules, intermediate filaments and septins, which are well known for their roles in cell division, shape and movement — have important functions in innate immunity and cellular self-defence. Investigations using cellular and animal models have shown that these cytoskeletal proteins are crucial for sensing bacteria and for mobilizing effector mechanisms to eliminate them. In this Review, we highlight the emerging roles of the cytoskeleton as a structural determinant of cell-autonomous host defence. PMID:26292640

Transcriptome and proteome dynamics in chemostat culture reveal how Campylobacter jejuni modulates metabolism, stress responses and virulence factors upon changes in oxygen availability

PubMed Central

Guccione, Edward J.; Kendall, John J.; Hitchcock, Andrew; Garg, Nitanshu; White, Michael A.; Mulholland, Francis; Poole, Robert K.

2017-01-01

Summary Campylobacter jejuni, the most frequent cause of food‐borne bacterial gastroenteritis worldwide, is a microaerophile that has to survive high environmental oxygen tensions, adapt to oxygen limitation in the intestine and resist host oxidative attack. Here, oxygen‐dependent changes in C. jejuni physiology were studied at constant growth rate using carbon (serine)‐limited continuous chemostat cultures. We show that a perceived aerobiosis scale can be calibrated by the acetate excretion flux, which becomes zero when metabolism is fully aerobic (100% aerobiosis). Transcriptome changes in a downshift experiment from 150% to 40% aerobiosis revealed many novel oxygen‐regulated genes and highlighted re‐modelling of the electron transport chains. A label‐free proteomic analysis showed that at 40% aerobiosis, many proteins involved in host colonisation (e.g., PorA, CadF, FlpA, CjkT) became more abundant. PorA abundance increased steeply below 100% aerobiosis. In contrast, several citric‐acid cycle enzymes, the peptide transporter CstA, PEB1 aspartate/glutamate transporter, LutABC lactate dehydrogenase and PutA proline dehydrogenase became more abundant with increasing aerobiosis. We also observed a co‐ordinated response of oxidative stress protection enzymes and Fe‐S cluster biogenesis proteins above 100% aerobiosis. Our approaches reveal key virulence factors that respond to restricted oxygen availability and specific transporters and catabolic pathways activated with increasing aerobiosis. PMID:28892295

Transcriptome analysis reveals the host response to Schmallenberg virus in bovine cells and antagonistic effects of the NSs protein.

PubMed

Blomström, Anne-Lie; Gu, Quan; Barry, Gerald; Wilkie, Gavin; Skelton, Jessica K; Baird, Margaret; McFarlane, Melanie; Schnettler, Esther; Elliott, Richard M; Palmarini, Massimo; Kohl, Alain

2015-04-19

Schmallenberg virus (SBV) is a member of the Orthobunyavirus genus (Bunyaviridae family) causing malformations and abortions in ruminants. Although, as for other members of this family/genus, the non-structural protein NSs has been shown to be an interferon antagonist, very little is known regarding the overall inhibitory effects and targets of orthobunyavirus NSs proteins on host gene expression during infection. Therefore, using RNA-seq this study describes changes to the transcriptome of primary bovine cells following infection with Schmallenberg virus (SBV) or with a mutant lacking the non-structural protein NSs (SBVdelNSs) providing a detailed comparison of the effect of NSs expression on the host cell. The sequence reads from all samples (uninfected cells, SBV and SBVdelNSs) assembled well to the bovine host reference genome (on average 87.43% of the reads). During infection with SBVdelNSs, 649 genes were differentially expressed compared to uninfected cells (78.7% upregulated) and many of these were known antiviral and IFN-stimulated genes. On the other hand, only nine genes were differentially expressed in SBV infected cells compared to uninfected control cells, demonstrating the strong inhibitory effect of NSs on cellular gene expression. However, the majority of the genes that were expressed during SBV infection are involved in restriction of viral replication and spread indicating that SBV does not completely manage to shutdown the host antiviral response. In this study we show the effects of SBV NSs on the transcriptome of infected cells as well as the cellular response to wild type SBV. Although NSs is very efficient in shutting down genes of the host innate response, a number of possible antiviral factors were identified. Thus the data from this study can serve as a base for more detailed mechanistic studies of SBV and other orthobunyaviruses.

Bacillus anthracis Overcomes an Amino Acid Auxotrophy by Cleaving Host Serum Proteins

PubMed Central

Terwilliger, Austen; Swick, Michelle C.; Pflughoeft, Kathryn J.; Pomerantsev, Andrei; Lyons, C. Rick; Koehler, Theresa M.

2015-01-01

ABSTRACT Bacteria sustain an infection by acquiring nutrients from the host to support replication. The host sequesters these nutrients as a growth-restricting strategy, a concept termed “nutritional immunity.” Historically, the study of nutritional immunity has centered on iron uptake because many bacteria target hemoglobin, an abundant circulating protein, as an iron source. Left unresolved are the mechanisms that bacteria use to attain other nutrients from host sources, including amino acids. We employed a novel medium designed to mimic the chemical composition of human serum, and we show here that Bacillus anthracis, the causative agent of anthrax disease, proteolyzes human hemoglobin to liberate essential amino acids which enhance its growth. This property can be traced to the actions of InhA1, a secreted metalloprotease, and extends to at least three other serum proteins, including serum albumin. The results suggest that we must also consider proteolysis of key host proteins to be a way for bacterial pathogens to attain essential nutrients, and we provide an experimental framework to determine the host and bacterial factors involved in this process. IMPORTANCE The mechanisms by which bacterial pathogens acquire nutrients during infection are poorly understood. Here we used a novel defined medium that approximates the chemical composition of human blood serum, blood serum mimic (BSM), to better model the nutritional environment that pathogens encounter during bacteremia. Removing essential amino acids from BSM revealed that two of the most abundant proteins in blood—hemoglobin and serum albumin—can satiate the amino acid requirement for Bacillus anthracis, the causative agent of anthrax. We further demonstrate that hemoglobin is proteolyzed by the secreted protease InhA1. These studies highlight that common blood proteins can be a nutrient source for bacteria. They also challenge the historical view that hemoglobin is solely an iron source for bacterial pathogens. PMID:25962917

Distribution and habitat utilization of the gopher tortoise tick (Amblyomma tuberculatum) in southern Mississippi

USGS Publications Warehouse

Ennen, Joshua R.; Qualls, Carl P.

2011-01-01

The distribution of the gopher tortoise tick (Amblyomma tuberculatum) has been considered intrinsically linked to the distribution of its primary host, gopher tortoises (Gopherus polyphemus). However, the presence of G. polyphemus does not always equate to the presence of A. tuberculatum. There is a paucity of data on the ecology, habitat preferences, and distribution of A. tuberculatum. The goals of this study were to assess the distribution of A. tuberculatum in southern Mississippi and to determine which, if any, habitat parameters explain the distribution pattern of A. tuberculatum. During 2006-2007, we examined 13 G. polyphemus populations in southern Mississippi for the presence of A. tuberculatum, and we measured a suite of habitat parameters at each site. Only 23% of the G. polyphemus populations supported A. tuberculatum, suggesting a more restricted distribution than its host. The results of our multivariate analyses identified several habitat variables, e.g., depth of sand and percentage of sand in the topsoil and burrow apron, as being important in discriminating between sites with, and without, A. tuberculatum. Amblyomma tuberculatum was only found at sites with a mean sand depth of >100 cm and a mean percentage of topsoil and burrow apron sand composition >94.0 and 92.4, respectively. Thus, environmental factors, and not just its host's range, seem to influence the distribution of A. tuberculatum.

Distribution and habitat utilization of the gopher tortoise tick (Amblyomma tuberculatum) in Southern Mississippi

USGS Publications Warehouse

Ennen, J.R.; Qualls, C.P.

2011-01-01

The distribution of the gopher tortoise tick (Amblyomma tuberculatum) has been considered intrinsically linked to the distribution of its primary host, gopher tortoises (Gopherus polyphemus). However, the presence of G. polyphemus does not always equate to the presence of A. tuberculatum. There is a paucity of data on the ecology, habitat preferences, and distribution of A. tuberculatum. The goals of this study were to assess the distribution of A. tuberculatum in southern Mississippi and to determine which, if any, habitat parameters explain the distribution pattern of A. tuberculatum. During 2006-2007, we examined 13 G. polyphemus populations in southern Mississippi for the presence of A. tuberculatum, and we measured a suite of habitat parameters at each site. Only 23% of the G. polyphemus populations supported A. tuberculatum, suggesting a more restricted distribution than its host. The results of our multivariate analyses identified several habitat variables, e.g., depth of sand and percentage of sand in the topsoil and burrow apron, as being important in discriminating between sites with, and without, A. tuberculatum. Amblyomma tuberculatum was only found at sites with a mean sand depth of >100 cm and a mean percentage of topsoil and burrow apron sand composition >94.0 and 92.4, respectively. Thus, environmental factors, and not just its host's range, seem to influence the distribution of A. tuberculatum. ?? American Society of Parasitologists 2011.

Chapter 11. Community analysis-based methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, Y.; Wu, C.H.; Andersen, G.L.

2010-05-01

Microbial communities are each a composite of populations whose presence and relative abundance in water or other environmental samples are a direct manifestation of environmental conditions, including the introduction of microbe-rich fecal material and factors promoting persistence of the microbes therein. As shown by culture-independent methods, different animal-host fecal microbial communities appear distinctive, suggesting that their community profiles can be used to differentiate fecal samples and to potentially reveal the presence of host fecal material in environmental waters. Cross-comparisons of microbial communities from different hosts also reveal relative abundances of genetic groups that can be used to distinguish sources. Inmore » increasing order of their information richness, several community analysis methods hold promise for MST applications: phospholipid fatty acid (PLFA) analysis, denaturing gradient gel electrophoresis (DGGE), terminal restriction fragment length polymorphism (TRFLP), cloning/sequencing, and PhyloChip. Specific case studies involving TRFLP and PhyloChip approaches demonstrate the ability of community-based analyses of contaminated waters to confirm a diagnosis of water quality based on host-specific marker(s). The success of community-based MST for comprehensively confirming fecal sources relies extensively upon using appropriate multivariate statistical approaches. While community-based MST is still under evaluation and development as a primary diagnostic tool, results presented herein demonstrate its promise. Coupled with its inherently comprehensive ability to capture an unprecedented amount of microbiological data that is relevant to water quality, the tools for microbial community analysis are increasingly accessible, and community-based approaches have unparalleled potential for translation into rapid, perhaps real-time, monitoring platforms.« less

Reconstruction of the Evolutionary History and Dispersal of Usutu Virus, a Neglected Emerging Arbovirus in Europe and Africa

PubMed Central

Engel, Dimitri; Jöst, Hanna; Wink, Michael; Börstler, Jessica; Bosch, Stefan; Garigliany, Mutien-Marie; Jöst, Artur; Czajka, Christina; Lühken, Renke; Ziegler, Ute; Groschup, Martin H.; Pfeffer, Martin; Becker, Norbert; Schmidt-Chanasit, Jonas

2016-01-01

ABSTRACT Usutu virus (USUV), one of the most neglected Old World encephalitic flaviviruses, causes epizootics among wild and captive birds and sporadic infection in humans. The dynamics of USUV spread and evolution in its natural hosts are unknown. Here, we present the phylogeny and evolutionary history of all available USUV strains, including 77 newly sequenced complete genomes from a variety of host species at a temporal and spatial scaled resolution. The results showed that USUV can be classified into six distinct lineages and that the most recent common ancestor of the recent European epizootics emerged in Africa at least 500 years ago. We demonstrated that USUV was introduced regularly from Africa into Europe in the last 50 years, and the genetic diversity of European lineages is shaped primarily by in situ evolution, while the African lineages have been driven by extensive gene flow. Most of the amino acid changes are deleterious polymorphisms removed by purifying selection, with adaptive evolution restricted to the NS5 gene and several others evolving under episodic directional selection, indicating that the ecological or immunological factors were mostly the key determinants of USUV dispersal and outbreaks. Host-specific mutations have been detected, while the host transition analysis identified mosquitoes as the most likely origin of the common ancestor and birds as the source of the recent European USUV lineages. Our results suggest that the major migratory bird flyways could predict the continental and intercontinental dispersal patterns of USUV and that migratory birds might act as potential long-distance dispersal vehicles. PMID:26838717

HCMV triggers frequent and persistent UL40-specific unconventional HLA-E-restricted CD8 T-cell responses with potential autologous and allogeneic peptide recognition.

PubMed

Jouand, Nicolas; Bressollette-Bodin, Céline; Gérard, Nathalie; Giral, Magali; Guérif, Pierrick; Rodallec, Audrey; Oger, Romain; Parrot, Tiphaine; Allard, Mathilde; Cesbron-Gautier, Anne; Gervois, Nadine; Charreau, Béatrice

2018-04-01

Immune response against human cytomegalovirus (HCMV) includes a set of persistent cytotoxic NK and CD8 T cells devoted to eliminate infected cells and to prevent reactivation. CD8 T cells against HCMV antigens (pp65, IE1) presented by HLA class-I molecules are well characterized and they associate with efficient virus control. HLA-E-restricted CD8 T cells targeting HCMV UL40 signal peptides (HLA-EUL40) have recently emerged as a non-conventional T-cell response also observed in some hosts. The occurrence, specificity and features of HLA-EUL40 CD8 T-cell responses remain mostly unknown. Here, we detected and quantified these responses in blood samples from healthy blood donors (n = 25) and kidney transplant recipients (n = 121) and we investigated the biological determinants involved in their occurrence. Longitudinal and phenotype ex vivo analyses were performed in comparison to HLA-A*02/pp65-specific CD8 T cells. Using a set of 11 HLA-E/UL40 peptide tetramers we demonstrated the presence of HLA-EUL40 CD8 αβT cells in up to 32% of seropositive HCMV+ hosts that may represent up to 38% of total circulating CD8 T-cells at a time point suggesting a strong expansion post-infection. Host's HLA-A*02 allele, HLA-E *01:01/*01:03 genotype and sequence of the UL40 peptide from the infecting strain are major factors affecting the incidence of HLA-EUL40 CD8 T cells. These cells are effector memory CD8 (CD45RAhighROlow, CCR7-, CD27-, CD28-) characterized by a low level of PD-1 expression. HLA-EUL40 responses appear early post-infection and display a broad, unbiased, Vβ repertoire. Although induced in HCMV strain-dependent, UL4015-23-specific manner, HLA-EUL40 CD8 T cells are reactive toward a broader set of nonapeptides varying in 1-3 residues including most HLA-I signal peptides. Thus, HCMV induces strong and life-long lasting HLA-EUL40 CD8 T cells with potential allogeneic or/and autologous reactivity that take place selectively in at least a third of infections according to virus strain and host HLA concordance.

Parasite spread at the domestic animal - wildlife interface: anthropogenic habitat use, phylogeny and body mass drive risk of cat and dog flea (Ctenocephalides spp.) infestation in wild mammals.

PubMed

Clark, Nicholas J; Seddon, Jennifer M; Šlapeta, Jan; Wells, Konstans

2018-01-08

Spillover of parasites at the domestic animal - wildlife interface is a pervasive threat to animal health. Cat and dog fleas (Ctenocephalides felis and C. canis) are among the world's most invasive and economically important ectoparasites. Although both species are presumed to infest a diversity of host species across the globe, knowledge on their distributions in wildlife is poor. We built a global dataset of wild mammal host associations for cat and dog fleas, and used Bayesian hierarchical models to identify traits that predict wildlife infestation probability. We complemented this by calculating functional-phylogenetic host specificity to assess whether fleas are restricted to hosts with similar evolutionary histories, diet or habitat niches. Over 130 wildlife species have been found to harbour cat fleas, representing nearly 20% of all mammal species sampled for fleas. Phylogenetic models indicate cat fleas are capable of infesting a broad diversity of wild mammal species through ecological fitting. Those that use anthropogenic habitats are at highest risk. Dog fleas, by contrast, have been recorded in 31 mammal species that are primarily restricted to certain phylogenetic clades, including canids, felids and murids. Both flea species are commonly reported infesting mammals that are feral (free-roaming cats and dogs) or introduced (red foxes, black rats and brown rats), suggesting the breakdown of barriers between wildlife and invasive reservoir species will increase spillover at the domestic animal - wildlife interface. Our empirical evidence shows that cat fleas are incredibly host-generalist, likely exhibiting a host range that is among the broadest of all ectoparasites. Reducing wild species' contact rates with domestic animals across natural and anthropogenic habitats, together with mitigating impacts of invasive reservoir hosts, will be crucial for reducing invasive flea infestations in wild mammals.

Getting the Hologenome Concept Right: an Eco-Evolutionary Framework for Hosts and Their Microbiomes.

PubMed

Theis, Kevin R; Dheilly, Nolwenn M; Klassen, Jonathan L; Brucker, Robert M; Baines, John F; Bosch, Thomas C G; Cryan, John F; Gilbert, Scott F; Goodnight, Charles J; Lloyd, Elisabeth A; Sapp, Jan; Vandenkoornhuyse, Philippe; Zilber-Rosenberg, Ilana; Rosenberg, Eugene; Bordenstein, Seth R

2016-01-01

Given the complexity of host-microbiota symbioses, scientists and philosophers are asking questions at new biological levels of hierarchical organization-what is a holobiont and hologenome? When should this vocabulary be applied? Are these concepts a null hypothesis for host-microbe systems or limited to a certain spectrum of symbiotic interactions such as host-microbial coevolution? Critical discourse is necessary in this nascent area, but productive discourse requires that skeptics and proponents use the same lexicon. For instance, critiquing the hologenome concept is not synonymous with critiquing coevolution, and arguing that an entity is not a primary unit of selection dismisses the fact that the hologenome concept has always embraced multilevel selection. Holobionts and hologenomes are incontrovertible, multipartite entities that result from ecological, evolutionary, and genetic processes at various levels. They are not restricted to one special process but constitute a wider vocabulary and framework for host biology in light of the microbiome.

Influenza virus sequence feature variant type analysis: evidence of a role for NS1 in influenza virus host range restriction.

PubMed

Noronha, Jyothi M; Liu, Mengya; Squires, R Burke; Pickett, Brett E; Hale, Benjamin G; Air, Gillian M; Galloway, Summer E; Takimoto, Toru; Schmolke, Mirco; Hunt, Victoria; Klem, Edward; García-Sastre, Adolfo; McGee, Monnie; Scheuermann, Richard H

2012-05-01

Genetic drift of influenza virus genomic sequences occurs through the combined effects of sequence alterations introduced by a low-fidelity polymerase and the varying selective pressures experienced as the virus migrates through different host environments. While traditional phylogenetic analysis is useful in tracking the evolutionary heritage of these viruses, the specific genetic determinants that dictate important phenotypic characteristics are often difficult to discern within the complex genetic background arising through evolution. Here we describe a novel influenza virus sequence feature variant type (Flu-SFVT) approach, made available through the public Influenza Research Database resource (www.fludb.org), in which variant types (VTs) identified in defined influenza virus protein sequence features (SFs) are used for genotype-phenotype association studies. Since SFs have been defined for all influenza virus proteins based on known structural, functional, and immune epitope recognition properties, the Flu-SFVT approach allows the rapid identification of the molecular genetic determinants of important influenza virus characteristics and their connection to underlying biological functions. We demonstrate the use of the SFVT approach to obtain statistical evidence for effects of NS1 protein sequence variations in dictating influenza virus host range restriction.

Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid.

PubMed

McClelland, Michael; Sanderson, Kenneth E; Clifton, Sandra W; Latreille, Phil; Porwollik, Steffen; Sabo, Aniko; Meyer, Rekha; Bieri, Tamberlyn; Ozersky, Phil; McLellan, Michael; Harkins, C Richard; Wang, Chunyan; Nguyen, Christine; Berghoff, Amy; Elliott, Glendoria; Kohlberg, Sara; Strong, Cindy; Du, Feiyu; Carter, Jason; Kremizki, Colin; Layman, Dan; Leonard, Shawn; Sun, Hui; Fulton, Lucinda; Nash, William; Miner, Tracie; Minx, Patrick; Delehaunty, Kim; Fronick, Catrina; Magrini, Vincent; Nhan, Michael; Warren, Wesley; Florea, Liliana; Spieth, John; Wilson, Richard K

2004-12-01

Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae).

Probing individual environmental bacteria for viruses by using microfluidic digital PCR.

PubMed

Tadmor, Arbel D; Ottesen, Elizabeth A; Leadbetter, Jared R; Phillips, Rob

2011-07-01

Viruses may very well be the most abundant biological entities on the planet. Yet neither metagenomic studies nor classical phage isolation techniques have shed much light on the identity of the hosts of most viruses. We used a microfluidic digital polymerase chain reaction (PCR) approach to physically link single bacterial cells harvested from a natural environment with a viral marker gene. When we implemented this technique on the microbial community residing in the termite hindgut, we found genus-wide infection patterns displaying remarkable intragenus selectivity. Viral marker allelic diversity revealed restricted mixing of alleles between hosts, indicating limited lateral gene transfer of these alleles despite host proximity. Our approach does not require culturing hosts or viruses and provides a method for examining virus-bacterium interactions in many environments.

Probing Individual Environmental Bacteria for Viruses by Using Microfluidic Digital PCR

PubMed Central

Tadmor, Arbel D.; Ottesen, Elizabeth A.; Leadbetter, Jared R.; Phillips, Rob

2012-01-01

Viruses may very well be the most abundant biological entities on the planet. Yet neither metagenomic studies nor classical phage isolation techniques have shed much light on the identity of the hosts of most viruses. We used a microfluidic digital polymerase chain reaction (PCR) approach to physically link single bacterial cells harvested from a natural environment with a viral marker gene. When we implemented this technique on the microbial community residing in the termite hindgut, we found genus-wide infection patterns displaying remarkable intragenus selectivity. Viral marker allelic diversity revealed restricted mixing of alleles between hosts, indicating limited lateral gene transfer of these alleles despite host proximity. Our approach does not require culturing hosts or viruses and provides a method for examining virus-bacterium interactions in many environments. PMID:21719670

An examination of environmental factors associated with Myxobolus cerebralis infection of wild trout in Pennsylvania

USGS Publications Warehouse

Kaeser, Adam J.; Rasmussen, Charlotte; Sharpe, William E.

2006-01-01

Salmonid whirling disease, caused by the myxosporean parasite Myxobolus cerebralis, was first observed in the United States in 1956 in central Pennsylvania. The parasite was subsequently discovered at several culture facilities throughout the state, and widespread distribution of this parasite via the stocking of subclinically infected brook trout Salvelinus fontinalis, rainbow trout Oncorhynchus mykiss, and brown trout Salmo trutta has been assumed. Although no monitoring of wild populations occurred until the late 1970s, it is a common belief that epizootics of whirling disease, now realized in the Intermountain West, are unlikely to have occurred in Pennsylvania. We conducted a review of historical information and a synoptic survey aimed at identifying factors that may prevent whirling disease outbreak in this region, reasoning that such information might be useful in identifying management strategies for populations affected by this parasite. Here we present data on parasite prevalence, fish populations, stream attributes, and the genetics of Tubifex tubifex (the obligate oligochaete host for the parasite) to evaluate various hypotheses proposed for low whirling disease impact in the region. We did not find clear associations between factors such as stream gradient, the genetics of T. tubifexpopulations, or the composition of resident trout populations and the pattern of M. cerebralis occurrence in Pennsylvania. We suggest that this pattern may be best explained by the association between T. tubifex host populations and point sources of organic enrichment. The potential restriction of T. tubifex populations to locations near sources of organic enrichment may be a factor in explaining why whirling disease has not been observed to cause population declines among wild trout in this region and should be further investigated.

Host apolipoprotein B messenger RNA-editing enzyme catalytic polypeptide-like 3G is an innate defensive factor and drug target against hepatitis C virus.

PubMed

Peng, Zong-Gen; Zhao, Zhi-Yun; Li, Yan-Ping; Wang, Yu-Ping; Hao, Lan-Hu; Fan, Bo; Li, Yu-Huan; Wang, Yue-Ming; Shan, Yong-Qiang; Han, Yan-Xing; Zhu, Yan-Ping; Li, Jian-Rui; You, Xue-Fu; Li, Zhuo-Rong; Jiang, Jian-Dong

2011-04-01

Host cellular factor apolipoprotein B messenger RNA (mRNA)-editing enzyme catalytic polypeptide-like 3G (hA3G) is a cytidine deaminase that inhibits a group of viruses including human immunodeficiency virus-1 (HIV-1). In the continuation of our research on hA3G, we found that hA3G stabilizing compounds significantly inhibited hepatitis C virus (HCV) replication. Therefore, this study investigated the role of hA3G in HCV replication. Introduction of external hA3G into HCV-infected Huh7.5 human hepatocytes inhibited HCV replication; knockdown of endogenous hA3G enhanced HCV replication. Exogenous HIV-1 virion infectivity factor (Vif) decreased intracellular hA3G and therefore enhanced HCV proliferation, suggesting that the presence of Vif might be an explanation for the HIV-1/HCV coinfection often observed in HIV-1(+) individuals. Treatment of the HCV-infected Huh7.5 cells with RN-5 or IMB-26, two known hA3G stabilizing compounds, increased intracellular hA3G and accordingly inhibited HCV replication. The compounds inhibit HCV through increasing the level of hA3G incorporated into HCV particles, but not through inhibiting HCV enzymes. However, G/A hypermutation in the HCV genome were not detected, suggesting a new antiviral mechanism of hA3G in HCV, different from that in HIV-1. Stabilization of hA3G by RN-5 was safe in vivo. hA3G appears to be a cellular restrict factor against HCV and could be a potential target for drug discovery. 2011 American Association for the Study of Liver Diseases.

Human and rat gut microbiome composition is maintained following sleep restriction

PubMed Central

Zhang, Shirley L.; Bai, Lei; Goel, Namni; Bailey, Aubrey; Jang, Christopher J.; Bushman, Frederic D.; Meerlo, Peter; Dinges, David F.; Sehgal, Amita

2017-01-01

Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is associated with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurological and cognitive impairments. Shifts in gut microbiome composition have also been associated with the same pathologies; therefore, we hypothesized that sleep restriction may perturb the gut microbiome to contribute to a disease state. In this study, we examined the fecal microbiome by using a cross-species approach in both rat and human studies of sleep restriction. We used DNA from hypervariable regions (V1-V2) of 16S bacteria rRNA to define operational taxonomic units (OTUs) of the microbiome. Although the OTU richness of the microbiome is decreased by sleep restriction in rats, major microbial populations are not altered. Only a single OTU, TM7-3a, was found to increase with sleep restriction of rats. In the human microbiome, we find no overt changes in the richness or composition induced by sleep restriction. Together, these results suggest that the microbiome is largely resistant to changes during sleep restriction. PMID:28179566

Human and rat gut microbiome composition is maintained following sleep restriction.

PubMed

Zhang, Shirley L; Bai, Lei; Goel, Namni; Bailey, Aubrey; Jang, Christopher J; Bushman, Frederic D; Meerlo, Peter; Dinges, David F; Sehgal, Amita

2017-02-21

Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is associated with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurological and cognitive impairments. Shifts in gut microbiome composition have also been associated with the same pathologies; therefore, we hypothesized that sleep restriction may perturb the gut microbiome to contribute to a disease state. In this study, we examined the fecal microbiome by using a cross-species approach in both rat and human studies of sleep restriction. We used DNA from hypervariable regions (V1-V2) of 16S bacteria rRNA to define operational taxonomic units (OTUs) of the microbiome. Although the OTU richness of the microbiome is decreased by sleep restriction in rats, major microbial populations are not altered. Only a single OTU, TM7-3a, was found to increase with sleep restriction of rats. In the human microbiome, we find no overt changes in the richness or composition induced by sleep restriction. Together, these results suggest that the microbiome is largely resistant to changes during sleep restriction.

Evolution in action: climate change, biodiversity dynamics and emerging infectious disease.

PubMed

Hoberg, Eric P; Brooks, Daniel R

2015-04-05

Climatological variation and ecological perturbation have been pervasive drivers of faunal assembly, structure and diversification for parasites and pathogens through recurrent events of geographical and host colonization at varying spatial and temporal scales of Earth history. Episodic shifts in climate and environmental settings, in conjunction with ecological mechanisms and host switching, are often critical determinants of parasite diversification, a view counter to more than a century of coevolutionary thinking about the nature of complex host-parasite assemblages. Parasites are resource specialists with restricted host ranges, yet shifts onto relatively unrelated hosts are common during phylogenetic diversification of parasite lineages and directly observable in real time. The emerging Stockholm Paradigm resolves this paradox: Ecological Fitting (EF)--phenotypic flexibility and phylogenetic conservatism in traits related to resource use, most notably host preference--provides many opportunities for rapid host switching in changing environments, without the evolution of novel host-utilization capabilities. Host shifts via EF fuel the expansion phase of the Oscillation Hypothesis of host range and speciation and, more generally, the generation of novel combinations of interacting species within the Geographic Mosaic Theory of Coevolution. In synergy, an environmental dynamic of Taxon Pulses establishes an episodic context for host and geographical colonization. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

7 CFR 301.92-2 - Restricted, regulated, and associated articles; lists of proven hosts and associated plant taxa.

Code of Federal Regulations, 2012 CFR

2012-01-01

... willow *Sequoia sempervirens Coast redwood *Syringa vulgaris Lilac *Taxus baccata European yew... Phytophthora ramorum: Abies concolor White fir Abies grandis Grand fir Abies magnifica Red fir Acer circinatum...

7 CFR 301.92-2 - Restricted, regulated, and associated articles; lists of proven hosts and associated plant taxa.

Code of Federal Regulations, 2013 CFR

2013-01-01

... willow *Sequoia sempervirens Coast redwood *Syringa vulgaris Lilac *Taxus baccata European yew... Phytophthora ramorum: Abies concolor White fir Abies grandis Grand fir Abies magnifica Red fir Acer circinatum...

7 CFR 301.92-2 - Restricted, regulated, and associated articles; lists of proven hosts and associated plant taxa.

Code of Federal Regulations, 2014 CFR

2014-01-01

... willow *Sequoia sempervirens Coast redwood *Syringa vulgaris Lilac *Taxus baccata European yew... Phytophthora ramorum: Abies concolor White fir Abies grandis Grand fir Abies magnifica Red fir Acer circinatum...

7 CFR 301.92-2 - Restricted, regulated, and associated articles; lists of proven hosts and associated plant taxa.

Code of Federal Regulations, 2010 CFR

2010-01-01

... willow *Sequoia sempervirens Coast redwood *Syringa vulgaris Lilac *Taxus baccata European yew... Phytophthora ramorum: Abies concolor White fir Abies grandis Grand fir Abies magnifica Red fir Acer circinatum...

7 CFR 301.92-2 - Restricted, regulated, and associated articles; lists of proven hosts and associated plant taxa.

Code of Federal Regulations, 2011 CFR

2011-01-01

... willow *Sequoia sempervirens Coast redwood *Syringa vulgaris Lilac *Taxus baccata European yew... Phytophthora ramorum: Abies concolor White fir Abies grandis Grand fir Abies magnifica Red fir Acer circinatum...

Host and parasite morphology influence congruence between host and parasite phylogenies.

PubMed

Sweet, Andrew D; Bush, Sarah E; Gustafsson, Daniel R; Allen, Julie M; DiBlasi, Emily; Skeen, Heather R; Weckstein, Jason D; Johnson, Kevin P

2018-03-23

Comparisons of host and parasite phylogenies often show varying degrees of phylogenetic congruence. However, few studies have rigorously explored the factors driving this variation. Multiple factors such as host or parasite morphology may govern the degree of phylogenetic congruence. An ideal analysis for understanding the factors correlated with congruence would focus on a diverse host-parasite system for increased variation and statistical power. In this study, we focused on the Brueelia-complex, a diverse and widespread group of feather lice that primarily parasitise songbirds. We generated a molecular phylogeny of the lice and compared this tree with a phylogeny of their avian hosts. We also tested for the contribution of each host-parasite association to the overall congruence. The two trees overall were significantly congruent, but the contribution of individual associations to this congruence varied. To understand this variation, we developed a novel approach to test whether host, parasite or biogeographic factors were statistically associated with patterns of congruence. Both host plumage dimorphism and parasite ecomorphology were associated with patterns of congruence, whereas host body size, other plumage traits and biogeography were not. Our results lay the framework for future studies to further elucidate how these factors influence the process of host-parasite coevolution. Copyright © 2018 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction

PubMed Central

Mano, Miguel; Ippodrino, Rudy; Zentilin, Lorena; Zacchigna, Serena; Giacca, Mauro

2015-01-01

Viral vectors based on the adeno-associated virus (AAV) hold great promise for in vivo gene transfer; several unknowns, however, still limit the vectors’ broader and more efficient application. Here, we report the results of a high-throughput, whole-genome siRNA screening aimed at identifying cellular factors regulating AAV transduction. We identified 1,483 genes affecting vector efficiency more than 4-fold and up to 50-fold, either negatively or positively. Most of these factors have not previously been associated to AAV infection. The most effective siRNAs were independent from the virus serotype or analyzed cell type and were equally evident for single-stranded and self-complementary AAV vectors. A common characteristic of the most effective siRNAs was the induction of cellular DNA damage and activation of a cell cycle checkpoint. This information can be exploited for the development of more efficient AAV-based gene delivery procedures. Administration of the most effective siRNAs identified by the screening to the liver significantly improved in vivo AAV transduction efficiency. PMID:26305933

The plant cell nucleus: a true arena for the fight between plants and pathogens.

PubMed

Deslandes, Laurent; Rivas, Susana

2011-01-01

Communication between the cytoplasm and the nucleus is a fundamental feature shared by both plant and animal cells. Cellular factors involved in the transport of macromolecules through the nuclear envelope, including nucleoporins, importins and Ran-GTP related components, are conserved among a variety of eukaryotic systems. Interestingly, mutations in these nuclear components compromise resistance signalling, illustrating the importance of nucleocytoplasmic trafficking in plant innate immunity. Indeed, spatial restriction of defence regulators by the nuclear envelope and stimulus-induced nuclear translocation constitute an important level of defence-associated gene regulation in plants. A significant number of effectors from different microbial pathogens are targeted to the plant cell nucleus. In addition, key host factors, including resistance proteins, immunity components, transcription factors and transcriptional regulators shuttle between the cytoplasm and the nucleus, and their level of nuclear accumulation determines the output of the defence response, further confirming the crucial role played by the nucleus during the interaction between plants and pathogens. Here, we discuss recent findings that situate the nucleus at the frontline of the mutual recognition between plants and invading microbes.

Identification of host factors potentially involved in RTM-mediated resistance during potyvirus long distance movement.

PubMed

Sofer, Luc; Cabanillas, Daniel Garcia; Gayral, Mathieu; Téplier, Rachèle; Pouzoulet, Jérôme; Ducousso, Marie; Dufin, Laurène; Bréhélin, Claire; Ziegler-Graff, Véronique; Brault, Véronique; Revers, Frédéric

2017-07-01

The long distance movement of potyviruses is a poorly understood step of the viral cycle. Only factors inhibiting this process, referred to as "Restricted TEV Movement" (RTM), have been identified in Arabidopsis thaliana. On the virus side, the potyvirus coat protein (CP) displays determinants required for long-distance movement and for RTM-based resistance breaking. However, the potyvirus CP was previously shown not to interact with the RTM proteins. We undertook the identification of Arabidopsis factors which directly interact with either the RTM proteins or the CP of lettuce mosaic virus (LMV). An Arabidopsis cDNA library generated from companion cells was screened with LMV CP and RTM proteins using the yeast two-hybrid system. Fourteen interacting proteins were identified. Two of them were shown to interact with CP and the RTM proteins suggesting that a multiprotein complex could be formed between the RTM proteins and virions or viral ribonucleoprotein complexes. Co-localization experiments in Nicotiana benthamiana showed that most of the viral and cellular protein pairs co-localized at the periphery of chloroplasts which suggests a putative role for plastids in this process.

A Genetic Screen Reveals that Synthesis of 1,4-Dihydroxy-2-Naphthoate (DHNA), but Not Full-Length Menaquinone, Is Required for Listeria monocytogenes Cytosolic Survival.

PubMed

Chen, Grischa Y; McDougal, Courtney E; D'Antonio, Marc A; Portman, Jonathan L; Sauer, John-Demian

2017-03-21

Through unknown mechanisms, the host cytosol restricts bacterial colonization; therefore, only professional cytosolic pathogens are adapted to colonize this host environment. Listeria monocytogenes is a Gram-positive intracellular pathogen that is highly adapted to colonize the cytosol of both phagocytic and nonphagocytic cells. To identify L. monocytogenes determinants of cytosolic survival, we designed and executed a novel screen to isolate L. monocytogenes mutants with cytosolic survival defects. Multiple mutants identified in the screen were defective for synthesis of menaquinone (MK), an essential molecule in the electron transport chain. Analysis of an extensive set of MK biosynthesis and respiratory chain mutants revealed that cellular respiration was not required for cytosolic survival of L. monocytogenes but that, instead, synthesis of 1,4-dihydroxy-2-naphthoate (DHNA), an MK biosynthesis intermediate, was essential. Recent discoveries showed that modulation of the central metabolism of both host and pathogen can influence the outcome of host-pathogen interactions. Our results identify a potentially novel function of the MK biosynthetic intermediate DHNA and specifically highlight how L. monocytogenes metabolic adaptations promote cytosolic survival and evasion of host immunity. IMPORTANCE Cytosolic bacterial pathogens, such as Listeria monocytogenes and Francisella tularensis , are exquisitely evolved to colonize the host cytosol in a variety of cell types. Establishing an intracellular niche shields these pathogens from effectors of humoral immunity, grants access to host nutrients, and is essential for pathogenesis. Through yet-to-be-defined mechanisms, the host cytosol restricts replication of non-cytosol-adapted bacteria, likely through a combination of cell autonomous defenses (CADs) and nutritional immunity. Utilizing a novel genetic screen, we identified determinants of L. monocytogenes cytosolic survival and virulence and identified a role for the synthesis of the menaquinone precursor 1,4-dihydroxy-2-naphthoate (DHNA) in cytosolic survival. Together, these data begin to elucidate adaptations that allow cytosolic pathogens to survive in their intracellular niches. Copyright © 2017 Chen et al.

Participation restrictions in ambulatory amyotrophic lateral sclerosis patients: Physical and psychological factors.

PubMed

Van Groenestijn, Annerieke C; Schröder, Carin D; Kruitwagen-Van Reenen, Esther T; Van Den Berg, Leonard H; Visser-Meily, Johanna M A

2017-11-01

The aim of this study was to assess the prevalence of participation restrictions in ambulatory patients with amyotrophic lateral sclerosis (ALS) and to identify physical and psychological contributory factors. In this cross-sectional study, self-reported participation restrictions of 72 ambulatory ALS patients were assessed using the social health status dimension (SIPSOC) of the Sickness Impact Profile (SIP-68). Associations between SIPSOC and physical functioning, psychological factors, and demographic factors were analyzed using hierarchical regression analyses. Ninety-two percent of the patients reported participation restrictions; 54.9% could be explained by physical functioning; psychological factors accounted for 8.1% of the variance. Lung capacity, functional mobility, fatigue, and helplessness were independently associated with participation restrictions. Ambulatory ALS patients have participation restrictions, which may be influenced if early ALS care is directed toward lung capacity, functional mobility, fatigue, and feelings of helplessness. Muscle Nerve 56: 912-918, 2017. © 2017 Wiley Periodicals, Inc.

Human Adenovirus Core Protein V Is Targeted by the Host SUMOylation Machinery To Limit Essential Viral Functions.

PubMed

Freudenberger, Nora; Meyer, Tina; Groitl, Peter; Dobner, Thomas; Schreiner, Sabrina

2018-02-15

Human adenoviruses (HAdV) are nonenveloped viruses containing a linear, double-stranded DNA genome surrounded by an icosahedral capsid. To allow proper viral replication, the genome is imported through the nuclear pore complex associated with viral core proteins. Until now, the role of these incoming virion proteins during the early phase of infection was poorly understood. The core protein V is speculated to bridge the core and the surrounding capsid. It binds the genome in a sequence-independent manner and localizes in the nucleus of infected cells, accumulating at nucleoli. Here, we show that protein V contains conserved SUMO conjugation motifs (SCMs). Mutation of these consensus motifs resulted in reduced SUMOylation of the protein; thus, protein V represents a novel target of the host SUMOylation machinery. To understand the role of protein V SUMO posttranslational modification during productive HAdV infection, we generated a replication-competent HAdV with SCM mutations within the protein V coding sequence. Phenotypic analyses revealed that these SCM mutations are beneficial for adenoviral replication. Blocking protein V SUMOylation at specific sites shifts the onset of viral DNA replication to earlier time points during infection and promotes viral gene expression. Simultaneously, the altered kinetics within the viral life cycle are accompanied by more efficient proteasomal degradation of host determinants and increased virus progeny production than that observed during wild-type infection. Taken together, our studies show that protein V SUMOylation reduces virus growth; hence, protein V SUMOylation represents an important novel aspect of the host antiviral strategy to limit virus replication and thereby points to potential intervention strategies. IMPORTANCE Many decades of research have revealed that HAdV structural proteins promote viral entry and mainly physical stability of the viral genome in the capsid. Our work over the last years showed that this concept needs expansion as the functions are more diverse. We showed that capsid protein VI regulates the antiviral response by modulation of the transcription factor Daxx during infection. Moreover, core protein VII interacts with SPOC1 restriction factor, which is beneficial for efficient viral gene expression. Here, we were able to show that core protein V also represents a novel substrate of the host SUMOylation machinery and contains several conserved SCMs; mutation of these consensus motifs reduced SUMOylation of the protein. Unexpectedly, we observed that introducing these mutations into HAdV promotes adenoviral replication. In conclusion, we offer novel insights into adenovirus core proteins and provide evidence that SUMOylation of HAdV factors regulates replication efficiency. Copyright © 2018 American Society for Microbiology.

Innate and intrinsic antiviral immunity in Drosophila

PubMed Central

Mussabekova, Assel; Daeffler, Laurent; Imler, Jean-Luc

2017-01-01

The fruitfly Drosophila melanogaster has been a valuable model to investigate the genetic mechanisms of innate immunity. Initially focused on the resistance to bacteria and fungi, these studies have been extended to include antiviral immunity over the last decade. Like all living organisms, insects are continually exposed to viruses and have developed efficient defense mechanisms. We review here our current understanding on antiviral host-defense in fruit flies. A major antiviral defense in Drosophila is RNA interference, in particular the small interfering (si) RNA pathway. In addition, complex inducible responses and restriction factors contribute to the control of infections. Some of the genes involved in these pathways have been conserved through evolution, highlighting loci that may account for susceptibility to viral infections in humans. Other genes are not conserved and represent species-specific innovations. PMID:28102430

Innate and intrinsic antiviral immunity in Drosophila.

PubMed

Mussabekova, Assel; Daeffler, Laurent; Imler, Jean-Luc

2017-06-01

The fruit fly Drosophila melanogaster has been a valuable model to investigate the genetic mechanisms of innate immunity. Initially focused on the resistance to bacteria and fungi, these studies have been extended to include antiviral immunity over the last decade. Like all living organisms, insects are continually exposed to viruses and have developed efficient defense mechanisms. We review here our current understanding on antiviral host defense in fruit flies. A major antiviral defense in Drosophila is RNA interference, in particular the small interfering (si) RNA pathway. In addition, complex inducible responses and restriction factors contribute to the control of infections. Some of the genes involved in these pathways have been conserved through evolution, highlighting loci that may account for susceptibility to viral infections in humans. Other genes are not conserved and represent species-specific innovations.

10 CFR 63.43 - License specification.

Code of Federal Regulations, 2010 CFR

2010-01-01

...: (1) Restrictions as to the physical and chemical form and radioisotopic content of radioactive waste..., considering the physical characteristics of both the waste and the host rock. (4) Requirements relating to... the provisions relating to organization and management, procedures, recordkeeping, review and audit...

HIV-1 Nef interferes with host cell motility by deregulation of Cofilin.

PubMed

Stolp, Bettina; Reichman-Fried, Michal; Abraham, Libin; Pan, Xiaoyu; Giese, Simone I; Hannemann, Sebastian; Goulimari, Polyxeni; Raz, Erez; Grosse, Robert; Fackler, Oliver T

2009-08-20

HIV-1 Nef is a key factor in AIDS pathogenesis. Here, we report that Nef potently inhibits motility of fibroblasts and chemotaxis of HIV-1-infected primary human T lymphocytes toward the chemokines SDF-1alpha, CCL-19, and CCL-21 ex vivo. Furthermore, Nef inhibits guided motility of zebrafish primordial germ cells toward endogenous SDF-1a in vivo. These migration defects result from Nef-mediated inhibition of the actin remodeling normally triggered by migratory stimuli. Nef strongly induces phosphorylation of cofilin, inactivating this evolutionarily conserved actin-depolymerizing factor that promotes cell motility when unphosphorylated. Nef-dependent cofilin deregulation requires association of Nef with the cellular kinase Pak2. Disruption of Nef-Pak2 association restores the cofilin phosphorylation levels and actin remodeling that facilitate cell motility. We conclude that HIV-1 Nef alters Pak2 function, which directly or indirectly inactivates cofilin, thereby restricting migration of infected T lymphocytes as part of a strategy to optimize immune evasion and HIV-1 replication.

Institutional barriers and strategies to health promotion: perspectives and experiences of Cape Verdean women health promoters.

PubMed

De Jesus, Maria

2010-06-01

Health promoters are critical resources in improving health care access and in providing culturally-responsive health education and interventions to members of medically underserved communities. Little is known about the barriers that impede their health-promoting practices and the strategies used to overcome these barriers. In-depth, semi-structured interviews were conducted with nine Cape Verdean women health promoters to examine their perspectives on barriers and strategies to health promotion. Findings revealed how their health promotion practice is influenced by a host of institutional barriers, including insufficient program funding, restrictive institutional policies, and a lack of culturally and linguistically appropriate health resources. Adaptive and resistant strategies used to counterbalance these barriers included forming supportive internal and external alliances, having a good mentor, and "making noise." A complete and effective model of health promotion must embrace not only individual-level factors, but also macro-level factors, thus emphasizing the need for institutional change to enhance health-promoting practices.

Institutional Barriers and Strategies to Health Promotion: Perspectives and Experiences of Cape Verdean Women Health Promoters

PubMed Central

2015-01-01

Background Health promoters are critical resources in improving health care access and in providing culturally-responsive health education and interventions to members of medically underserved communities. Little is known about the barriers that impede their health-promoting practices and the strategies used to overcome these barriers. Methods In-depth, semi-structured interviews were conducted with nine Cape Verdean women health promoters to examine their perspectives on barriers and strategies to health promotion. Results Findings revealed how their health promotion practice is influenced by a host of institutional barriers, including insufficient program funding, restrictive institutional policies, and a lack of culturally and linguistically appropriate health resources. Adaptive and resistant strategies used to counterbalance these barriers included forming supportive internal and external alliances, having a good mentor, and “making noise.” Discussion A complete and effective model of health promotion must embrace not only individual-level factors, but also macro-level factors, thus emphasizing the need for institutional change to enhance health-promoting practices. PMID:18307042

Ebola virus: the role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever.

PubMed

Bray, Mike; Geisbert, Thomas W

2005-08-01

Ebola hemorrhagic fever is a severe viral infection characterized by fever, shock and coagulation defects. Recent studies in macaques show that major features of illness are caused by effects of viral replication on macrophages and dendritic cells. Infected macrophages produce proinflammatory cytokines, chemokines and tissue factor, attracting additional target cells and inducing vasodilatation, increased vascular permeability and disseminated intravascular coagulation. However, they cannot restrict viral replication, possibly because of suppression of interferon responses. Infected dendritic cells also secrete proinflammatory mediators, but cannot initiate antigen-specific responses. In consequence, virus disseminates to these and other cell types throughout the body, causing multifocal necrosis and a syndrome resembling septic shock. Massive "bystander" apoptosis of natural killer and T cells further impairs immunity. These findings suggest that modifying host responses would be an effective therapeutic strategy, and treatment of infected macaques with a tissue-factor inhibitor reduced both inflammation and viral replication and improved survival.

AGE restriction in diabetes mellitus: a paradigm shift

PubMed Central

Vlassara, Helen; Striker, Gary E.

2013-01-01

Persistently elevated oxidative stress and inflammation precede or occur during the development of type 1 or type 2 diabetes mellitus and precipitate devastating complications. Given the rapidly increasing incidence of diabetes mellitus and obesity in the space of a few decades, new genetic mutations are unlikely to be the cause, instead pointing to environmental initiators. A hallmark of contemporary culture is a preference for thermally processed foods, replete with pro-oxidant advanced glycation endproducts (AGEs). These molecules are appetite-increasing and, thus, efficient enhancers of overnutrition (which promotes obesity) and oxidant overload (which promotes inflammation). Studies of genetic and nongenetic animal models of diabetes mellitus suggest that suppression of host defenses, under sustained pressure from food-derived AGEs, may potentially shift homeostasis towards a higher basal level of oxidative stress, inflammation and injury of both insulin-producing and insulin-responsive cells. This sequence promotes both types of diabetes mellitus. Reducing basal oxidative stress by AGE restriction in mice, without energy or nutrient change, reinstates host defenses, alleviates inflammation, prevents diabetes mellitus, vascular and renal complications and extends normal lifespan. Studies in healthy humans and in those with diabetes mellitus show that consumption of high amounts of food-related AGEs is a determinant of insulin resistance and inflammation and that AGE restriction improves both. This Review focuses on AGEs as novel initiators of oxidative stress that precedes, rather than results from, diabetes mellitus. Therapeutic gains from AGE restriction constitute a paradigm shift. PMID:21610689

Targeting Host Factors to Treat West Nile and Dengue Viral Infections

PubMed Central

Krishnan, Manoj N.; Garcia-Blanco, Mariano A.

2014-01-01

West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans. PMID:24517970

Targeting host factors to treat West Nile and dengue viral infections.

PubMed

Krishnan, Manoj N; Garcia-Blanco, Mariano A

2014-02-10

West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

Roles of Pro-viral Host Factors in Mosquito-Borne Flavivirus Infections.

PubMed

Campos, Rafael K; Garcia-Blanco, Mariano A; Bradrick, Shelton S

2017-07-09

Identification and analysis of viral host factors is a growing area of research which aims to understand the how viruses molecularly interface with the host cell. Investigations into flavivirus-host interactions has led to new discoveries in viral and cell biology, and will potentially bolster strategies to control the important diseases caused by these pathogens. Here, we address the current knowledge of prominent host factors required for the flavivirus life-cycle and mechanisms by which they promote infection.

The Impact of Prophage on the Equilibria and Stability of Phage and Host

NASA Astrophysics Data System (ADS)

Yu, Pei; Nadeem, Alina; Wahl, Lindi M.

2017-06-01

In this paper, we present a bacteriophage model that includes prophage, that is, phage genomes that are incorporated into the host cell genome. The general model is described by an 18-dimensional system of ordinary differential equations. This study focuses on asymptotic behaviour of the model, and thus the system is reduced to a simple six-dimensional model, involving uninfected host cells, infected host cells and phage. We use dynamical system theory to explore the dynamic behaviour of the model, studying in particular the impact of prophage on the equilibria and stability of phage and host. We employ bifurcation and stability theory, centre manifold and normal form theory to show that the system has multiple equilibrium solutions which undergo a series of bifurcations, finally leading to oscillating motions. Numerical simulations are presented to illustrate and confirm the analytical predictions. The results of this study indicate that in some parameter regimes, the host cell population may drive the phage to extinction through diversification, that is, if multiple types of host emerge; this prediction holds even if the phage population is likewise diverse. This parameter regime is restricted, however, if infecting phage are able to recombine with prophage sequences in the host cell genome.

Aneurysmal SubArachnoid Hemorrhage—Red Blood Cell Transfusion And Outcome (SAHaRA): a pilot randomised controlled trial protocol

PubMed Central

English, Shane W; Fergusson, D; Chassé, M; Lauzier, F; Griesdale, D; Algird, A; Kramer, A; Tinmouth, A; Lum, C; Sinclair, J; Marshall, S; Dowlatshahi, D; Boutin, A; Pagliarello, G; McIntyre, L A

2016-01-01

Introduction Anaemia is common in aneurysmal subarachnoid haemorrhage (aSAH) and is a potential critical modifiable factor affecting secondary injury. Despite physiological evidence and management guidelines that support maintaining a higher haemoglobin level in patients with aSAH, current practice is one of a more restrictive approach to transfusion. The goal of this multicentre pilot trial is to determine the feasibility of successfully conducting a red blood cell (RBC) transfusion trial in adult patients with acute aSAH and anaemia (Hb ≤100 g/L), comparing a liberal transfusion strategy (Hb ≤100 g/L) with a restrictive strategy (Hb ≤80 g/L) on the combined rate of death and severe disability at 12 months. Methods Design This is a multicentre open-label randomised controlled pilot trial at 5 academic tertiary care centres. Population We are targeting adult aSAH patients within 14 days of their initial bleed and with anaemia (Hb ≤110 g/L). Randomisation Central computer-generated randomisation, stratified by centre, will be undertaken from the host centre. Randomisation into 1 of the 2 treatment arms will occur when the haemoglobin levels of eligible patients fall to ≤100 g/L. Intervention Patients will be randomly assigned to either a liberal (threshold: Hb ≤100 g/L) or a restrictive transfusion strategy (threshold: Hb ≤80 g/L). Outcome Primary: Centre randomisation rate over the study period. Secondary: (1) transfusion threshold adherence; (2) study RBC transfusion protocol adherence; and (3) outcome assessment including vital status at hospital discharge, modified Rankin Score at 6 and 12 months and Functional Independence Measure and EuroQOL Quality of Life Scale scores at 12 months. Outcome measures will be reported in aggregate. Ethics and dissemination The study protocol has been approved by the host centre (OHSN-REB 20150433-01H). This study will determine the feasibility of conducting the large pragmatic RCT comparing 2 RBC transfusion strategies examining the effect of a liberal strategy on 12-month outcome following aSAH. Trial registration number NCT02483351; Pre-results. PMID:27927658

Pathogen Trojan Horse Delivers Bioactive Host Protein to Alter Maize Anther Cell Behavior in Situ.

PubMed

van der Linde, Karina; Timofejeva, Ljudmilla; Egger, Rachel L; Ilau, Birger; Hammond, Reza; Teng, Chong; Meyers, Blake C; Doehlemann, Gunther; Walbot, Virginia

2018-03-01

Small proteins are crucial signals during development, host defense, and physiology. The highly spatiotemporal restricted functions of signaling proteins remain challenging to study in planta. The several month span required to assess transgene expression, particularly in flowers, combined with the uncertainties from transgene position effects and ubiquitous or overexpression, makes monitoring of spatiotemporally restricted signaling proteins lengthy and difficult. This situation could be rectified with a transient assay in which protein deployment is tightly controlled spatially and temporally in planta to assess protein functions, timing, and cellular targets as well as to facilitate rapid mutagenesis to define functional protein domains. In maize ( Zea mays ), secreted ZmMAC1 (MULTIPLE ARCHESPORIAL CELLS1) was proposed to trigger somatic niche formation during anther development by participating in a ligand-receptor module. Inspired by Homer's Trojan horse myth, we engineered a protein delivery system that exploits the secretory capabilities of the maize smut fungus Ustilago maydis , to allow protein delivery to individual cells in certain cell layers at precise time points. Pathogen-supplied ZmMAC1 cell-autonomously corrected both somatic cell division and differentiation defects in mutant Zm mac1-1 anthers. These results suggest that exploiting host-pathogen interactions may become a generally useful method for targeting host proteins to cell and tissue types to clarify cellular autonomy and to analyze steps in cell responses. © 2018 American Society of Plant Biologists. All rights reserved.

Within-host evolution decreases virulence in an opportunistic bacterial pathogen.

PubMed

Mikonranta, Lauri; Mappes, Johanna; Laakso, Jouni; Ketola, Tarmo

2015-08-19

Pathogens evolve in a close antagonistic relationship with their hosts. The conventional theory proposes that evolution of virulence is highly dependent on the efficiency of direct host-to-host transmission. Many opportunistic pathogens, however, are not strictly dependent on the hosts due to their ability to reproduce in the free-living environment. Therefore it is likely that conflicting selection pressures for growth and survival outside versus within the host, rather than transmission potential, shape the evolution of virulence in opportunists. We tested the role of within-host selection in evolution of virulence by letting a pathogen Serratia marcescens db11 sequentially infect Drosophila melanogaster hosts and then compared the virulence to strains that evolved only in the outside-host environment. We found that the pathogen adapted to both Drosophila melanogaster host and novel outside-host environment, leading to rapid evolutionary changes in the bacterial life-history traits including motility, in vitro growth rate, biomass yield, and secretion of extracellular proteases. Most significantly, selection within the host led to decreased virulence without decreased bacterial load while the selection lines in the outside-host environment maintained the same level of virulence with ancestral bacteria. This experimental evidence supports the idea that increased virulence is not an inevitable consequence of within-host adaptation even when the epidemiological restrictions are removed. Evolution of attenuated virulence could occur because of immune evasion within the host. Alternatively, rapid fluctuation between outside-host and within-host environments, which is typical for the life cycle of opportunistic bacterial pathogens, could lead to trade-offs that lower pathogen virulence.

Neutrophil-mediated inflammation in the pathogenesis of Clostridium difficile infections

PubMed Central

Jose, Shinsmon; Madan, Rajat

2016-01-01

Clostridium difficile is the most important cause of nosocomial infectious diarrhea in the western world. C. difficile infections are a major healthcare burden with approximately 500,000 new cases every year and an estimated annual cost of nearly $1 billion in the U.S. Furthermore, the infections are no longer restricted to health care facilities, and recent studies indicate spread of C. difficile infection to the community as well. The clinical spectrum of C. difficile infection ranges from asymptomatic colonization to severe diarrhea, fulminant colitis and death. This spectrum results from a complex interplay between bacterial virulence factors, the colonic microbiome and the host inflammatory response. The overall vigor of host inflammatory response is believed to be an important determinant of C. difficile disease severity, and a more robust immune response is associated with worse outcomes. Neutrophils are the primary cells that respond to C. difficile invasion and neutrophilic inflammation is the hallmark of C. difficile-associated disease. In this review, we will focus on the role of neutrophils (infiltration to infected tissue, pathogen clearance and resolution of inflammation) in the immuno-pathogenesis of C. difficile-associated disease (CDAD). PMID:27063896

Neutrophil-mediated inflammation in the pathogenesis of Clostridium difficile infections.

PubMed

Jose, Shinsmon; Madan, Rajat

2016-10-01

Clostridium difficile is the most important cause of nosocomial infectious diarrhea in the western world. C. difficile infections are a major healthcare burden with approximately 500,000 new cases every year and an estimated annual cost of nearly $1 billion in the U.S. Furthermore, the infections are no longer restricted to health care facilities, and recent studies indicate spread of C. difficile infection to the community as well. The clinical spectrum of C. difficile infection ranges from asymptomatic colonization to severe diarrhea, fulminant colitis and death. This spectrum results from a complex interplay between bacterial virulence factors, the colonic microbiome and the host inflammatory response. The overall vigor of host inflammatory response is believed to be an important determinant of C. difficile disease severity, and a more robust immune response is associated with worse outcomes. Neutrophils are the primary cells that respond to C. difficile invasion and neutrophilic inflammation is the hallmark of C. difficile-associated disease. In this review, we will focus on the role of neutrophils (infiltration to infected tissue, pathogen clearance and resolution of inflammation) in the immuno-pathogenesis of C. difficile-associated disease (CDAD). Copyright © 2016 Elsevier Ltd. All rights reserved.

Haemophilus Responses to Nutritional Immunity: Epigenetic and Morphological Contribution to Biofilm Architecture, Invasion, Persistence and Disease Severity

PubMed Central

Szelestey, Blake R.; Heimlich, Derek R.; Raffel, Forrest K.; Justice, Sheryl S.; Mason, Kevin M.

2013-01-01

In an effort to suppress microbial outgrowth, the host sequesters essential nutrients in a process termed nutritional immunity. However, inflammatory responses to bacterial insult can restore nutritional resources. Given that nutrient availability modulates virulence factor production and biofilm formation by other bacterial species, we hypothesized that fluctuations in heme-iron availability, particularly at privileged sites, would similarly influence Haemophilus biofilm formation and pathogenesis. Thus, we cultured Haemophilus through sequential heme-iron deplete and heme-iron replete media to determine the effect of transient depletion of internal stores of heme-iron on multiple pathogenic phenotypes. We observed that prior heme-iron restriction potentiates biofilm changes for at least 72 hours that include increased peak height and architectural complexity as compared to biofilms initiated from heme-iron replete bacteria, suggesting a mechanism for epigenetic responses that participate in the changes observed. Additionally, in a co-infection model for human otitis media, heme-iron restricted Haemophilus, although accounting for only 10% of the inoculum (90% heme-iron replete), represented up to 99% of the organisms recovered at 4 days. These data indicate that fluctuations in heme-iron availability promote a survival advantage during disease. Filamentation mediated by a SulA-related ortholog was required for optimal biofilm peak height and persistence during experimental otitis media. Moreover, severity of disease in response to heme-iron restricted Haemophilus was reduced as evidenced by lack of mucosal destruction, decreased erythema, hemorrhagic foci and vasodilatation. Transient restriction of heme-iron also promoted productive invasion events leading to the development of intracellular bacterial communities. Taken together, these data suggest that nutritional immunity, may, in fact, foster long-term phenotypic changes that better equip bacteria for survival at infectious sites. PMID:24130500

Electrostatic potential of human immunodeficiency virus type 2 and rhesus macaque simian immunodeficiency virus capsid proteins.

PubMed

Bozek, Katarzyna; Nakayama, Emi E; Kono, Ken; Shioda, Tatsuo

2012-01-01

Human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus isolated from a macaque monkey (SIVmac) are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (SIVsm). Despite their close similarity in genome structure, HIV-2 and SIVmac show different sensitivities to TRIM5α, a host restriction factor against retroviruses. The replication of HIV-2 strains is potently restricted by rhesus (Rh) monkey TRIM5α, while that of SIVmac strain 239 (SIVmac239) is not. Viral capsid protein is the determinant of this differential sensitivity to TRIM5α, as the HIV-2 mutant carrying SIVmac239 capsid protein evaded Rh TRIM5α-mediated restriction. However, the molecular determinants of this restriction mechanism are unknown. Electrostatic potential on the protein-binding site is one of the properties regulating protein-protein interactions. In this study, we investigated the electrostatic potential on the interaction surface of capsid protein of HIV-2 strain GH123 and SIVmac239. Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between α-helices 4 and 5 (L4/5). As L4/5 is one of the major determinants of Rh TRIM5α sensitivity of these viruses, the present results suggest that the binding site of the Rh TRIM5α may show complementarity to the HIV-2 GH123 capsid surface charge distribution.

Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health.

PubMed

Ha, Connie W Y; Lam, Yan Y; Holmes, Andrew J

2014-11-28

Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes (especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of rRNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging.

Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health

PubMed Central

Ha, Connie WY; Lam, Yan Y; Holmes, Andrew J

2014-01-01

Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes (especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of rRNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging. PMID:25469018

Atomic structure of the murine norovirus protruding domain and sCD300lf receptor complex.

PubMed

Kilic, Turgay; Koromyslova, Anna; Malak, Virginie; Hansman, Grant S

2018-03-21

Human noroviruses are the leading cause of acute gastroenteritis in human. Noroviruses also infect animals such as cow, mice, cat, and dog. How noroviruses bind and enter host cells is still incompletely understood. Recently, the type I transmembrane protein CD300lf was recently identified as the murine norovirus receptor, yet it is unclear how the virus capsid and receptor interact at the molecular level. In this study, we determined the X-ray crystal structure of the soluble CD300lf (sCD300lf) and murine norovirus capsid-protruding domain complex at 2.05 Å resolution. We found that the sCD300lf binding site is located on the topside of the protruding domain and involves a network of hydrophilic and hydrophobic interactions. The sCD300lf locked nicely into a complementary cavity on the protruding domain that is additionally coordinated with a positive surface charge on the sCD300lf and a negative surface charge on the protruding domain. Five of six protruding domain residues interacting with sCD300lf were maintained between different murine norovirus strains, suggesting that the sCD300lf was capable of binding to a highly conserved pocket. Moreover, a sequence alignment with other CD300 paralogs showed that the sCD300lf interacting residues were partially conserved in CD300ld, but variable in other CD300 family members, consistent with previously reported infection selectivity. Overall, these data provide insights into how a norovirus engages a protein receptor and will be important for a better understanding of selective recognition and norovirus attachment and entry mechanisms. IMPORTANCE Noroviruses exhibit exquisite host-range specificity due to species-specific interactions between the norovirus capsid protein and host molecules. Given this strict host-range restriction it has been unclear how the viruses are maintained within a species between relatively sporadic epidemics. While much data demonstrates that noroviruses can interact with carbohydrates, recent work has shown that expression of the protein CD300lf is both necessary and sufficient for murine norovirus infection of mice and binding of the virus to permissive cells. Importantly, the expression of this murine protein by human cells renders them fully permissive for murine norovirus infection, indicating that at least in this case host-range restriction is determined by molecular events that control receptor binding and entry. Defining the atomic-resolution interactions between the norovirus capsid protein and its cognate receptor is essential for a molecular understanding of host-range restriction and norovirus tropism. Copyright © 2018 American Society for Microbiology.

Immune modulation of host response to coccidiosis and necrotic enteritis to reduce antibiotics

USDA-ARS?s Scientific Manuscript database

Multiple challenges confront the rising demand for poultry food products, including governmental restrictions on the use of antibiotic growth promoters, high-density production conditions, waste management, and the emergence of infectious pathogens, particularly those that cause intestinal diseases....

22 CFR Appendix F to Part 62 - Information To Be Collected on Secondary School Student Host Family Applications

Code of Federal Regulations, 2012 CFR

2012-04-01

.... Identify those personal expenses expected to be covered by the student Diet: a. Does anyone in the family... a particular dietary restriction (ex. Vegetarian, Vegan, etc.)? (Y/N) d. Would the family provide...

22 CFR Appendix F to Part 62 - Information To Be Collected on Secondary School Student Host Family Applications

Code of Federal Regulations, 2013 CFR

2013-04-01

.... Identify those personal expenses expected to be covered by the student Diet: a. Does anyone in the family... a particular dietary restriction (ex. Vegetarian, Vegan, etc.)? (Y/N) d. Would the family provide...

22 CFR Appendix F to Part 62 - Information To Be Collected on Secondary School Student Host Family Applications

Code of Federal Regulations, 2014 CFR

2014-04-01

.... Identify those personal expenses expected to be covered by the student Diet: a. Does anyone in the family... a particular dietary restriction (ex. Vegetarian, Vegan, etc.)? (Y/N) d. Would the family provide...

22 CFR Appendix F to Part 62 - Information To Be Collected on Secondary School Student Host Family Applications

Code of Federal Regulations, 2011 CFR

2011-04-01

.... Identify those personal expenses expected to be covered by the student Diet: a. Does anyone in the family... a particular dietary restriction (ex. Vegetarian, Vegan, etc.)? (Y/N) d. Would the family provide...

22 CFR 3.11 - Responsibility of chief of mission to inform host government of restrictions on employees...

Code of Federal Regulations, 2010 CFR

2010-04-01

... not been tendered “in recognition of active field service in time of combat operations or awarded for... January of each year conduct a thorough and explicit program of orientation aimed at appropriate officials...

RELATIONSHIPS OF NATURAL ENEMIES AND NON-PREY FOODS

USDA-ARS?s Scientific Manuscript database

There are very few entomophagous species so maladapted as to rely on prey as their sole nutritional resource. Although a rich source of nutrients, prey/host availability to predators and parasitoids is restricted temporally by ephemeral population dynamics, spatial differences in microclimate, struc...

Single nucleotide polymorphisms in the Mycobacterium bovis genome resolve phylogenetic relationships

USDA-ARS?s Scientific Manuscript database

Mycobacterium bovis isolates carry restricted allelic variation yet exhibit a range of disease phenotypes and host preferences. Conventional genotyping methods target small hyper-variable regions of their genome and provide anonymous biallelic information insufficient to develop phylogeny. To resolv...

Induction of virulence factors in Giardia duodenalis independent of host attachment

PubMed Central

Emery, Samantha J.; Mirzaei, Mehdi; Vuong, Daniel; Pascovici, Dana; Chick, Joel M.; Lacey, Ernest; Haynes, Paul A.

2016-01-01

Giardia duodenalis is responsible for the majority of parasitic gastroenteritis in humans worldwide. Host-parasite interaction models in vitro provide insights into disease and virulence and help us to understand pathogenesis. Using HT-29 intestinal epithelial cells (IEC) as a model we have demonstrated that initial sensitisation by host secretions reduces proclivity for trophozoite attachment, while inducing virulence factors. Host soluble factors triggered up-regulation of membrane and secreted proteins, including Tenascins, Cathepsin-B precursor, cystatin, and numerous Variant-specific Surface Proteins (VSPs). By comparison, host-cell attached trophozoites up-regulated intracellular pathways for ubiquitination, reactive oxygen species (ROS) detoxification and production of pyridoxal phosphate (PLP). We reason that these results demonstrate early pathogenesis in Giardia involves two independent host-parasite interactions. Motile trophozoites respond to soluble secreted signals, which deter attachment and induce expression of virulence factors. Trophozoites attached to host cells, in contrast, respond by up-regulating intracellular pathways involved in clearance of ROS, thus anticipating the host defence response. PMID:26867958

Genome and transcriptome adaptation accompanying emergence of the definitive type 2 host-restricted Salmonella enterica serovar Typhimurium pathovar.

PubMed

Kingsley, Robert A; Kay, Sally; Connor, Thomas; Barquist, Lars; Sait, Leanne; Holt, Kathryn E; Sivaraman, Karthi; Wileman, Thomas; Goulding, David; Clare, Simon; Hale, Christine; Seshasayee, Aswin; Harris, Simon; Thomson, Nicholas R; Gardner, Paul; Rabsch, Wolfgang; Wigley, Paul; Humphrey, Tom; Parkhill, Julian; Dougan, Gordon

2013-08-27

Salmonella enterica serovar Typhimurium definitive type 2 (DT2) is host restricted to Columba livia (rock or feral pigeon) but is also closely related to S. Typhimurium isolates that circulate in livestock and cause a zoonosis characterized by gastroenteritis in humans. DT2 isolates formed a distinct phylogenetic cluster within S. Typhimurium based on whole-genome-sequence polymorphisms. Comparative genome analysis of DT2 94-213 and S. Typhimurium SL1344, DT104, and D23580 identified few differences in gene content with the exception of variations within prophages. However, DT2 94-213 harbored 22 pseudogenes that were intact in other closely related S. Typhimurium strains. We report a novel in silico approach to identify single amino acid substitutions in proteins that have a high probability of a functional impact. One polymorphism identified using this method, a single-residue deletion in the Tar protein, abrogated chemotaxis to aspartate in vitro. DT2 94-213 also exhibited an altered transcriptional profile in response to culture at 42°C compared to that of SL1344. Such differentially regulated genes included a number involved in flagellum biosynthesis and motility. IMPORTANCE Whereas Salmonella enterica serovar Typhimurium can infect a wide range of animal species, some variants within this serovar exhibit a more limited host range and altered disease potential. Phylogenetic analysis based on whole-genome sequences can identify lineages associated with specific virulence traits, including host adaptation. This study represents one of the first to link pathogen-specific genetic signatures, including coding capacity, genome degradation, and transcriptional responses to host adaptation within a Salmonella serovar. We performed comparative genome analysis of reference and pigeon-adapted definitive type 2 (DT2) S. Typhimurium isolates alongside phenotypic and transcriptome analyses, to identify genetic signatures linked to host adaptation within the DT2 lineage.

Assessment of Attention to Clothing and Impact of Its Restrictive Factors in Iranian Patients with Traumatic Spinal Cord Injury (ACIRF-SCI): Introduction of a New Questionnaire.

PubMed

Laleh, Leila; Latifi, Sahar; Koushki, Davood; Matin, Marzieh; Javidan, Abbas Norouzi; Yekaninejad, Mir Saeed

2015-01-01

Patients with spinal cord injury (SCI) deal with various restrictive factors regarding their clothing, such as disability and difficulty with access to shopping centers. We designed a questionnaire to assess attention to clothing and impact of its restrictive factors among Iranian patients with SCI (ACIRF-SCI). The ACIRF-SCI has 5 domains: functional, medical, attitude, aesthetic, and emotional. The first 3 domains reflect the impact of restrictive factors (factors that restrict attention to clothing), and the last 2 domains reflect attention to clothing and fashion. Functional restrictive factors include disability and dependence. Medical restrictive factors include existence of specific medical conditions that interfere with clothing choice. Construct validity was assessed by factorial analysis, and reliability was expressed by Cronbach's alpha. A total of 100 patients (75 men and 25 women) entered this study. Patients with a lower injury level had a higher total score (P < .0001), and similarly, patients with paraplegia had higher scores than those with tetraplegia (P < .0001), which illustrates an admissible discriminant validity. Postinjury duration was positively associated with total scores (r = 0.21, P = .04). Construct validity was 0.97, and Cronbach's alpha was 0.61. Iranian patients with SCI who have greater ability and independence experience a lower impact of restrictive factors related to clothing. The ACIRF-SCI reveals that this assumption is statistically significant, which shows its admissible discriminant validity. The measured construct validity (0.97) and reliability (internal consistency expressed by alpha = 0.61) are acceptable.

Assessment of Attention to Clothing and Impact of Its Restrictive Factors in Iranian Patients with Traumatic Spinal Cord Injury (ACIRF-SCI): Introduction of a New Questionnaire

PubMed Central

Laleh, Leila; Koushki, Davood; Matin, Marzieh; Javidan, Abbas Norouzi; Yekaninejad, Mir Saeed

2015-01-01

Background: Patients with spinal cord injury (SCI) deal with various restrictive factors regarding their clothing, such as disability and difficulty with access to shopping centers. Objectives: We designed a questionnaire to assess attention to clothing and impact of its restrictive factors among Iranian patients with SCI (ACIRF-SCI). Methods: The ACIRF-SCI has 5 domains: functional, medical, attitude, aesthetic, and emotional. The first 3 domains reflect the impact of restrictive factors (factors that restrict attention to clothing), and the last 2 domains reflect attention to clothing and fashion. Functional restrictive factors include disability and dependence. Medical restrictive factors include existence of specific medical conditions that interfere with clothing choice. Construct validity was assessed by factorial analysis, and reliability was expressed by Cronbach’s alpha. Results: A total of 100 patients (75 men and 25 women) entered this study. Patients with a lower injury level had a higher total score (P < .0001), and similarly, patients with paraplegia had higher scores than those with tetraplegia (P < .0001), which illustrates an admissible discriminant validity. Postinjury duration was positively associated with total scores (r = 0.21, P = .04). Construct validity was 0.97, and Cronbach’s alpha was 0.61. Conclusion: Iranian patients with SCI who have greater ability and independence experience a lower impact of restrictive factors related to clothing. The ACIRF-SCI reveals that this assumption is statistically significant, which shows its admissible discriminant validity. The measured construct validity (0.97) and reliability (internal consistency expressed by alpha = 0.61) are acceptable. PMID:26363593

Dispersal in patchy environments: effect on the prevalence of small mammal ectoparasites.

PubMed

Lundqvist, L; Edler, A

1987-01-01

Part-time ectoparasites on small mammals disperse via the habitat, while full-time parasites spread throughout the host population by direct contacts between host animals. It is therefore supposed that the effect of the natural environment is different for the two groups. This was studied as differences between observed and expected prevalence, the percentage of the infested host population, during different environmental conditions. Two possible mechanisms of such an effect were analysed, i.e. a) host selection and its change with host frequency and b) parasite migration and reproduction rates as reflected by the frequency distribution patterns on the hosts. As expected the prevalence of full-time ectoparasites (Anoplura and subfamily Laelapinae) could be predicted on the basis of host species frequencies during different environmental conditions, with the exception of one louse species (Hoplopleura acanthopus), because of its restricted distribution. Prediction was not possible for part-time ectoparasites (subfamily Hameogamasinae). Species of the subfamily Haemogamasinae were more catholic in host selection than species of Anoplura and subfamily Laelapinae. The haemogamasin mites changed host species to a greater extent than did Anoplura and Laelapinae. All haemogamasin mites had short-tailed frequency distribution patterns and all Anoplura and Laelapinae, except Hyperlaelaps microti, had long-tailed frequency distributions.

Has Sarcocystis neurona Dubey et al., 1991 (Sporozoa: Apicomplexa: Sarcocystidae) cospeciated with its intermediate hosts?

PubMed

Elsheikha, Hany M

2009-08-26

The question of how Sarcocystis neurona is able to overcome species barrier and adapt to new hosts is central to the understanding of both the evolutionary origin of S. neurona and the prediction of its field host range. Therefore, it is worth reviewing current knowledge on S. neurona host specificity. The available host range data for S. neurona are discussed in relation to a subject of evolutionary importance-specialist or generalist and its implications to understand the strategies of host adaptation. Current evidences demonstrate that a wide range of hosts exists for S. neurona. This parasite tends to be highly specific for its definitive host but much less so for its intermediate host (I.H.). The unique specificity of S. neurona for its definitive host may be mediated by a probable long coevolutionary relationship of the parasite and carnivores in a restricted ecological niche 'New World'. This might be taken as evidence that carnivores are the 'original' host group for S. neurona. Rather, the capacity of S. neurona to exploit an unusually large number of I.H. species probably indicates that S. neurona maintains non-specificity to its I.H. as an adaptive response to insure the survival of the parasite in areas in which the 'preferred' host is not available. This review concludes with the view that adaptation of S. neurona to a new host is a complex interplay that involves a large number of determinants.

CRISPR/Cas9 knockout of USP18 enhances type I IFN responsiveness and restricts HIV-1 infection in macrophages.

PubMed

Taylor, Jared P; Cash, Melanie N; Santostefano, Katherine E; Nakanishi, Mahito; Terada, Naohiro; Wallet, Mark A

2018-02-13

The IFN-stimulated gene ubiquitin-specific proteinase 18 (USP18) encodes a protein that negatively regulates T1 IFN signaling via stearic inhibition of JAK1 recruitment to the IFN-α receptor 2 subunit (IFNAR2). Here, we demonstrate that USP18 expression is induced by HIV-1 in a T1 IFN-dependent manner. Experimental depletion of USP18 by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing results in a significant restriction of HIV-1 replication in an induced pluripotent stem cell (iPSC)-derived macrophage model. In the absence of USP18, macrophages have increased responsiveness to stimulation with T1 IFNs with prolonged phosphorylation of STAT1 and STAT2 and increased expression of IFN-stimulated genes that are key for antiviral responses. Interestingly, HIV-1 requires some signaling through the T1 IFN receptor to replicate efficiently because a neutralizing antibody that inhibits T1 IFN activity reduces HIV-1 replication rate in monocyte-derived macrophages. USP18 induction by HIV-1 tunes the IFN response to optimal levels allowing for efficient transcription from the HIV-1 LTR promoter while minimizing the T1 IFN-induced antiviral response that would otherwise restrict viral replication and spread. Finally, iPSC and CRISPR/Cas9 gene targeting offer a powerful tool to study host factors that regulate innate immune responses. ©2018 Society for Leukocyte Biology.

Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at the Level of Virus Entry and at a Late Stage in the Virus Life Cycle

PubMed Central

Londrigan, Sarah L.; Short, Kirsty R.; Ma, Joel; Gillespie, Leah; Rockman, Steven P.; Brooks, Andrew G.

2015-01-01

ABSTRACT Airway epithelial cells are susceptible to infection with seasonal influenza A viruses (IAV), resulting in productive virus replication and release. Macrophages (MΦ) are also permissive to IAV infection; however, virus replication is abortive. Currently, it is unclear how productive infection of MΦ is impaired or the extent to which seasonal IAV replicate in MΦ. Herein, we compared mouse MΦ and epithelial cells for their ability to support genomic replication and transcription, synthesis of viral proteins, assembly of virions, and release of infectious progeny following exposure to genetically defined IAV. We confirm that seasonal IAV differ in their ability to utilize cell surface receptors for infectious entry and that this represents one level of virus restriction. Following virus entry, we demonstrate synthesis of all eight segments of genomic viral RNA (vRNA) and mRNA, as well as seven distinct IAV proteins, in IAV-infected mouse MΦ. Although newly synthesized hemagglutinin (HA) and neuraminidase (NA) glycoproteins are incorporated into the plasma membrane and expressed at the cell surface, electron microscopy confirmed that virus assembly was defective in IAV-infected MΦ, defining a second level of restriction late in the virus life cycle. IMPORTANCE Seasonal influenza A viruses (IAV) and highly pathogenic avian influenza viruses (HPAI) infect macrophages, but only HPAI replicate productively in these cells. Herein, we demonstrate that impaired virus uptake into macrophages represents one level of restriction limiting infection by seasonal IAV. Following uptake, seasonal IAV do not complete productive replication in macrophages, representing a second level of restriction. Using murine macrophages, we demonstrate that productive infection is blocked late in the virus life cycle, such that virus assembly is defective and newly synthesized virions are not released. These studies represent an important step toward identifying host-encoded factors that block replication of seasonal IAV, but not HPAI, in macrophages. PMID:26423941

Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at the Level of Virus Entry and at a Late Stage in the Virus Life Cycle.

PubMed

Londrigan, Sarah L; Short, Kirsty R; Ma, Joel; Gillespie, Leah; Rockman, Steven P; Brooks, Andrew G; Reading, Patrick C

2015-12-01

Airway epithelial cells are susceptible to infection with seasonal influenza A viruses (IAV), resulting in productive virus replication and release. Macrophages (MΦ) are also permissive to IAV infection; however, virus replication is abortive. Currently, it is unclear how productive infection of MΦ is impaired or the extent to which seasonal IAV replicate in MΦ. Herein, we compared mouse MΦ and epithelial cells for their ability to support genomic replication and transcription, synthesis of viral proteins, assembly of virions, and release of infectious progeny following exposure to genetically defined IAV. We confirm that seasonal IAV differ in their ability to utilize cell surface receptors for infectious entry and that this represents one level of virus restriction. Following virus entry, we demonstrate synthesis of all eight segments of genomic viral RNA (vRNA) and mRNA, as well as seven distinct IAV proteins, in IAV-infected mouse MΦ. Although newly synthesized hemagglutinin (HA) and neuraminidase (NA) glycoproteins are incorporated into the plasma membrane and expressed at the cell surface, electron microscopy confirmed that virus assembly was defective in IAV-infected MΦ, defining a second level of restriction late in the virus life cycle. Seasonal influenza A viruses (IAV) and highly pathogenic avian influenza viruses (HPAI) infect macrophages, but only HPAI replicate productively in these cells. Herein, we demonstrate that impaired virus uptake into macrophages represents one level of restriction limiting infection by seasonal IAV. Following uptake, seasonal IAV do not complete productive replication in macrophages, representing a second level of restriction. Using murine macrophages, we demonstrate that productive infection is blocked late in the virus life cycle, such that virus assembly is defective and newly synthesized virions are not released. These studies represent an important step toward identifying host-encoded factors that block replication of seasonal IAV, but not HPAI, in macrophages. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Restriction of Retrotransposon Mobilization in Schizosaccharomyces pombe by Transcriptional Silencing and Higher-Order Chromatin Organization

PubMed Central

Murton, Heather E.; Grady, Patrick J. R.; Chan, Tsun Ho; Cam, Hugh P.; Whitehall, Simon K.

2016-01-01

Uncontrolled propagation of retrotransposons is potentially detrimental to host genome integrity. Therefore, cells have evolved surveillance mechanisms to restrict the mobility of these elements. In Schizosaccharomyces pombe the Tf2 LTR retrotransposons are transcriptionally silenced and are also clustered in the nucleus into structures termed Tf bodies. Here we describe the impact of silencing and clustering on the mobility of an endogenous Tf2 element. Deletion of genes such as set1+ (histone H3 lysine 4 methyltransferase) or abp1+ (CENP-B homolog) that both alleviate silencing and clustering, result in a corresponding increase in mobilization. Furthermore, expression of constitutively active Sre1, a transcriptional activator of Tf2 elements, also alleviates clustering and induces mobilization. In contrast, clustering is not disrupted by loss of the HIRA histone chaperone, despite high levels of expression, and in this background, mobilization frequency is only marginally increased. Thus, mutations that compromise transcriptional silencing but not Tf bodies are insufficient to drive mobilization. Furthermore, analyses of mutant alleles that separate the transcriptional repression and clustering functions of Set1 are consistent with control of Tf2 propagation via a combination of silencing and spatial organization. Our results indicate that host surveillance mechanisms operate at multiple levels to restrict Tf2 retrotransposon mobilization. PMID:27343236

Cloning vector

DOEpatents

Guilfoyle, Richard A.; Smith, Lloyd M.

1994-01-01

A vector comprising a filamentous phage sequence containing a first copy of filamentous phage gene X and other sequences necessary for the phage to propagate is disclosed. The vector also contains a second copy of filamentous phage gene X downstream from a promoter capable of promoting transcription in a bacterial host. In a preferred form of the present invention, the filamentous phage is M13 and the vector additionally includes a restriction endonuclease site located in such a manner as to substantially inactivate the second gene X when a DNA sequence is inserted into the restriction site.

Cloning vector

DOEpatents

Guilfoyle, R.A.; Smith, L.M.

1994-12-27

A vector comprising a filamentous phage sequence containing a first copy of filamentous phage gene X and other sequences necessary for the phage to propagate is disclosed. The vector also contains a second copy of filamentous phage gene X downstream from a promoter capable of promoting transcription in a bacterial host. In a preferred form of the present invention, the filamentous phage is M13 and the vector additionally includes a restriction endonuclease site located in such a manner as to substantially inactivate the second gene X when a DNA sequence is inserted into the restriction site. 2 figures.

Dietary Carbohydrates and Childhood Functional Abdominal Pain.

PubMed

Chumpitazi, Bruno P; Shulman, Robert J

2016-01-01

Childhood functional gastrointestinal disorders (FGIDs) affect a large number of children throughout the world. Carbohydrates (which provide the majority of calories consumed in the Western diet) have been implicated both as culprits for the etiology of symptoms and as potential therapeutic agents (e.g., fiber) in childhood FGIDs. In this review, we detail how carbohydrate malabsorption may cause gastrointestinal symptoms (e.g., bloating) via the physiologic effects of both increased osmotic activity and increased gas production from bacterial fermentation. Several factors may play a role, including: (1) the amount of carbohydrate ingested; (2) whether ingestion is accompanied by a meal or other food; (3) the rate of gastric emptying (how quickly the meal enters the small intestine); (4) small intestinal transit time (the time it takes for a meal to enter the large intestine after first entering the small intestine); (5) whether the meal contains bacteria with enzymes capable of breaking down the carbohydrate; (6) colonic bacterial adaptation to one's diet, and (7) host factors such as the presence or absence of visceral hypersensitivity. By detailing controlled and uncontrolled trials, we describe how there is a general lack of strong evidence supporting restriction of individual carbohydrates (e.g., lactose, fructose) for childhood FGIDs. We review emerging evidence suggesting that a more comprehensive restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) may be effective. Finally, we review how soluble fiber (a complex carbohydrate) supplementation via randomized controlled intervention trials in childhood functional gastrointestinal disorders has demonstrated efficacy. © 2016 S. Karger AG, Basel.

Environment-related and host-related factors affecting the occurrence of lice on rodents in Central Europe.

PubMed

Stanko, Michal; Fričová, Jana; Miklisová, Dana; Khokhlova, Irina S; Krasnov, Boris R

2015-06-01

We studied the effects of environment- (habitat, season) and host-related (sex, body mass) factors on the occurrence of four species of lice (Insecta:Phthiraptera:Anoplura) on six rodent species (Rodentia:Muridae). We asked how these factors influence the occurrence of lice on an individual host and whether different rodent-louse associations demonstrate consistent trends in these effects. We found significant effects of at least one environment-related and at least one host-related factor on the louse occurrence in five of six host-louse associations. The effect of habitat was significant in two associations with the occurrence of lice being more frequent in lowland than in mountain habitats. The effect of season was significant in five associations with a higher occurrence of infestation during the warm season in four associations and the cold season in one association. Host sex affected significantly the infestation by lice in three associations with a higher frequency of infestation in males. Host body mass affected the occurrence of lice in all five associations, being negative in wood mice and positive in voles. In conclusion, lice were influenced not only by the host- but also by environment-related factors. The effects of the latter could be mediated via life history parameters of a host.

Comparative genomic analysis of Helicobacter pylori from Malaysia identifies three distinct lineages suggestive of differential evolution

PubMed Central

Kumar, Narender; Mariappan, Vanitha; Baddam, Ramani; Lankapalli, Aditya K.; Shaik, Sabiha; Goh, Khean-Lee; Loke, Mun Fai; Perkins, Tim; Benghezal, Mohammed; Hasnain, Seyed E.; Vadivelu, Jamuna; Marshall, Barry J.; Ahmed, Niyaz

2015-01-01

The discordant prevalence of Helicobacter pylori and its related diseases, for a long time, fostered certain enigmatic situations observed in the countries of the southern world. Variation in H. pylori infection rates and disease outcomes among different populations in multi-ethnic Malaysia provides a unique opportunity to understand dynamics of host–pathogen interaction and genome evolution. In this study, we extensively analyzed and compared genomes of 27 Malaysian H. pylori isolates and identified three major phylogeographic lineages: hspEastAsia, hpEurope and hpSouthIndia. The analysis of the virulence genes within the core genome, however, revealed a comparable pathogenic potential of the strains. In addition, we identified four genes limited to strains of East-Asian lineage. Our analyses identified a few strain-specific genes encoding restriction modification systems and outlined 311 core genes possibly under differential evolutionary constraints, among the strains representing different ethnic groups. The cagA and vacA genes also showed variations in accordance with the host genetic background of the strains. Moreover, restriction modification genes were found to be significantly enriched in East-Asian strains. An understanding of these variations in the genome content would provide significant insights into various adaptive and host modulation strategies harnessed by H. pylori to effectively persist in a host-specific manner. PMID:25452339

A Comparison of Epitope Repertoires Associated with Myasthenia Gravis in Humans and Nonhuman Hosts

PubMed Central

Vaughan, Kerrie; Kim, Yohan; Sette, Alessandro

2012-01-01

Here we analyzed the molecular targets associated with myasthenia gravis (MG) immune responses, enabled by an immune epitope database (IEDB) inventory of approximately 600 MG-related epitopes derived from 175 references. The vast majority of epitopes were derived from the α-subunit of human AChR suggesting that other MG-associated autoantigens should be investigated further. Human α-AChR was mostly characterized in humans, whereas reactivity primarily to T. californica AChR was examined in animal models. While the fine specificity of T-cell response was similar in the two systems, substantial antibody reactivity to the C-terminus was detected in the nonhuman system, but not in humans. Further analysis showed that the reactivity of nonhuman hosts to the C-terminus was eliminated when data were restricted to hosts tested in the context of autoimmune disease (spontaneous or induced), demonstrating that the epitopes recognized in humans and animals were shared when disease was present. Finally, we provided data subsets relevant to particular applications, including those associated with HLA typing or restriction, sets of epitopes recognized by monoclonal antibodies, and epitopes associated with modulation of immunity or disease. In conclusion, this analysis highlights gaps, differences, and similarities in the epitope repertoires of humans and animal models. PMID:23243503

NF-κB and enhancer-binding CREB protein scaffolded by CREB-binding protein (CBP)/p300 proteins regulate CD59 protein expression to protect cells from complement attack.

PubMed

Du, Yiqun; Teng, Xiaoyan; Wang, Na; Zhang, Xin; Chen, Jianfeng; Ding, Peipei; Qiao, Qian; Wang, Qingkai; Zhang, Long; Yang, Chaoqun; Yang, Zhangmin; Chu, Yiwei; Du, Xiang; Zhou, Xuhui; Hu, Weiguo

2014-01-31

The complement system can be activated spontaneously for immune surveillance or induced to clear invading pathogens, in which the membrane attack complex (MAC, C5b-9) plays a critical role. CD59 is the sole membrane complement regulatory protein (mCRP) that restricts MAC assembly. CD59, therefore, protects innocent host cells from attacks by the complement system, and host cells require the constitutive and inducible expression of CD59 to protect themselves from deleterious destruction by complement. However, the mechanisms that underlie CD59 regulation remain largely unknown. In this study we demonstrate that the widely expressed transcription factor Sp1 may regulate the constitutive expression of CD59, whereas CREB-binding protein (CBP)/p300 bridge NF-κB and CREB, which surprisingly functions as an enhancer-binding protein to induce the up-regulation of CD59 during in lipopolysaccharide (LPS)-triggered complement activation, thus conferring host defense against further MAC-mediated destruction. Moreover, individual treatment with LPS, TNF-α, and the complement activation products (sublytic MAC (SC5b-9) and C5a) could increase the expression of CD59 mainly by activating NF-κB and CREB signaling pathways. Together, our findings identify a novel gene regulation mechanism involving CBP/p300, NF-κB, and CREB; this mechanism suggests potential drug targets for controlling various complement-related human diseases.

Host and Bacterial Proteins That Repress Recruitment of LC3 to Shigella Early during Infection

PubMed Central

Baxt, Leigh A.; Goldberg, Marcia B.

2014-01-01

Shigella spp. are intracytosolic gram-negative pathogens that cause disease by invasion and spread through the colonic mucosa, utilizing host cytoskeletal components to form propulsive actin tails. We have previously identified the host factor Toca-1 as being recruited to intracellular S. flexneri and being required for efficient bacterial actin tail formation. We show that at early times during infection (40 min.), the type three-secreted effector protein IcsB recruits Toca-1 to intracellular bacteria and that recruitment of Toca-1 is associated with repression of recruitment of LC3, as well as with repression of recruitment of the autophagy marker NDP52, around these intracellular bacteria. LC3 is best characterized as a marker of autophagosomes, but also marks phagosomal membranes in the process LC3-associated phagocytosis. IcsB has previously been demonstrated to be required for S. flexneri evasion of autophagy at late times during infection (4–6 hr) by inhibiting binding of the autophagy protein Atg5 to the Shigella surface protein IcsA (VirG). Our results suggest that IcsB and Toca-1 modulation of LC3 recruitment restricts LC3-associated phagocytosis and/or LC3 recruitment to vacuolar membrane remnants. Together with published results, our findings suggest that IcsB inhibits innate immune responses in two distinct ways, first, by inhibiting LC3-associated phagocytosis and/or LC3 recruitment to vacuolar membrane remnants early during infection, and second, by inhibiting autophagy late during infection. PMID:24722587

Assessing the role of host traits as drivers of the abundance of long-lived parasites in fish-stock assessment studies.

PubMed

Braicovich, P E; Ieno, E N; Sáez, M; Despos, J; Timi, J T

2016-11-01

In order to identify the best tools for stock assessment studies using fish parasites as biological indicators, different host traits (size, mass and age and their interaction with sex) were evaluated as descriptors of cumulative patterns of both parasite abundance and infracommunity species richness. The effect of such variables was analysed for a sample of 265 specimens of Percophis brasiliensis caught in the Argentine Sea. The abundances and species richness were modelled using generalized linear mixed models (GLMMs) with negative binomial and Poisson distribution respectively. Due to collinearity, separate models were fitted for each of the three main explanatory variables (length, mass and age) to identify the optimal set of factors determining the parasite burdens. Optimal GLMMs were selected on the basis of the lowest Akaike information criteria, residual information and simulation studies based on 10 000 iterations. Results indicated that the covariates length and sex consistently appeared in the most parsimonious models suggesting that fish length seems to be a slightly better predictor than age or mass. The biological causes of these patterns are discussed. It is recommended to use fish length as a measure of growth and to restrict comparisons with fish of similar length or to incorporate length as covariate when comparing parasite burdens. Host sex should be also taken into account for those species sexually dimorphic in terms of morphology, behaviour or growth rates. © 2016 The Fisheries Society of the British Isles.

Transition metals at the host–pathogen interface: How Neisseria exploit human metalloproteins for acquiring iron and zinc

PubMed Central

Neumann, Wilma; Hadley, Rose C.; Nolan, Elizabeth M.

2017-01-01

Transition metals are essential nutrients for all organisms and important players in the host-microbe interaction. During bacterial infection, a tug-of-war between the host and microbe for nutrient metals occurs: the host innate immune system responds to the pathogen by reducing metal availability and the pathogen tries to outmaneuver this response. The outcome of this competition, which involves metal-sequestering host-defense proteins and microbial metal acquisition machinery, is an important variable for whether infection occurs. One strategy bacterial pathogens employ to overcome metal restriction involves hijacking abundant host metalloproteins. The obligate human pathogens Neisseria spp. express TonB-dependent transport systems that capture human metalloproteins, extract the bound metal ions, and deliver these nutrients into the bacterial cell. This Essay highlights structural and mechanistic investigations that provide insights into how Neisseria acquire iron from the Fe(III)-transport protein transferrin, the Fe(III)-chelating host-defense protein lactoferrin, and the oxygen-transport protein hemoglobin, and obtain zinc from the metal-sequestering antimicrobial protein calprotectin. PMID:28487398

Concomitant Lethal Mutagenesis of Human Immunodeficiency Virus Type 1

PubMed Central

Dapp, Michael J.; Holtz, Colleen M.; Mansky, Louis M.

2012-01-01

RNA virus population dynamics is complex, and sophisticated approaches are needed in many cases for therapeutic intervention. One such approach, termed lethal mutagenesis, is directed at targeting the virus population structure for extinction or error catastrophe. Previous studies have demonstrated the concept of this approach with human immunodeficiency virus type 1 (HIV-1) by use of chemical mutagens (i.e., 5-azacytidine) as well as by host factors with mutagenic properties (i.e., APOBEC3G). In this study, these two unrelated mutagenic agents were used concomitantly to investigate the interplay of these distinct mutagenic mechanisms. Specifically, an HIV-1 was produced from APOBEC3G (A3G)-expressing cells and used to infect permissive target cells treated with 5-azacytidine (5-AZC). Reduced viral infectivity and increased viral mutagenesis was observed with both the viral mutagen (i.e., G-to-C mutations) and the host restriction factor (i.e., G-to-A mutations); however, when combined, had complex interactions. Intriguingly, nucleotide sequence analysis revealed that concomitant HIV-1 exposure to both 5-AZC and A3G resulted in an increase of G-to-A viral mutagenesis at the expense of G-to-C mutagenesis. A3G catalytic activity was required for the diminution in G-to-C mutagenesis. Taken together, our findings provide the first demonstration for potentiation of the mutagenic effect of a cytosine analog by A3G expression, resulting in concomitant HIV-1 lethal mutagenesis. PMID:22426127

Molecular survey of the occurrence of Legionella spp., Mycobacterium spp., Pseudomonas aeruginosa, and amoeba hosts in two chloraminated drinking water distribution systems.

PubMed

Wang, Hong; Edwards, Marc; Falkinham, Joseph O; Pruden, Amy

2012-09-01

The spread of opportunistic pathogens via public water systems is of growing concern. The purpose of this study was to identify patterns of occurrence among three opportunistic pathogens (Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa) relative to biotic and abiotic factors in two representative chloraminated drinking water distribution systems using culture-independent methods. Generally, a high occurrence of Legionella (≥69.0%) and mycobacteria (100%), lower occurrence of L. pneumophila (≤20%) and M. avium (≤33.3%), and rare detection of Pseudomonas aeruginosa (≤13.3%) were observed in both systems according to quantitative PCR. Also, Hartmanella vermiformis was more prevalent than Acanthamoeba, both of which are known hosts for opportunistic pathogen amplification, the latter itself containing pathogenic members. Three-minute flushing served to distinguish distribution system water from plumbing in buildings (i.e., premise plumbing water) and resulted in reduced numbers of copies of Legionella, mycobacteria, H. vermiformis, and 16S rRNA genes (P < 0.05) while yielding distinct terminal restriction fragment polymorphism (T-RFLP) profiles of 16S rRNA genes. Within certain subgroups of samples, some positive correlations, including correlations of numbers of mycobacteria and total bacteria (16S rRNA genes), H. vermiformis and total bacteria, mycobacteria and H. vermiformis, and Legionella and H. vermiformis, were noted, emphasizing potential microbial ecological relationships. Overall, the results provide insight into factors that may aid in controlling opportunistic pathogen proliferation in real-world water systems.

Molecular Survey of the Occurrence of Legionella spp., Mycobacterium spp., Pseudomonas aeruginosa, and Amoeba Hosts in Two Chloraminated Drinking Water Distribution Systems

PubMed Central

Wang, Hong; Edwards, Marc; Falkinham, Joseph O.

2012-01-01

The spread of opportunistic pathogens via public water systems is of growing concern. The purpose of this study was to identify patterns of occurrence among three opportunistic pathogens (Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa) relative to biotic and abiotic factors in two representative chloraminated drinking water distribution systems using culture-independent methods. Generally, a high occurrence of Legionella (≥69.0%) and mycobacteria (100%), lower occurrence of L. pneumophila (≤20%) and M. avium (≤33.3%), and rare detection of Pseudomonas aeruginosa (≤13.3%) were observed in both systems according to quantitative PCR. Also, Hartmanella vermiformis was more prevalent than Acanthamoeba, both of which are known hosts for opportunistic pathogen amplification, the latter itself containing pathogenic members. Three-minute flushing served to distinguish distribution system water from plumbing in buildings (i.e., premise plumbing water) and resulted in reduced numbers of copies of Legionella, mycobacteria, H. vermiformis, and 16S rRNA genes (P < 0.05) while yielding distinct terminal restriction fragment polymorphism (T-RFLP) profiles of 16S rRNA genes. Within certain subgroups of samples, some positive correlations, including correlations of numbers of mycobacteria and total bacteria (16S rRNA genes), H. vermiformis and total bacteria, mycobacteria and H. vermiformis, and Legionella and H. vermiformis, were noted, emphasizing potential microbial ecological relationships. Overall, the results provide insight into factors that may aid in controlling opportunistic pathogen proliferation in real-world water systems. PMID:22752174

Pore water colloid properties in argillaceous sedimentary rocks.

PubMed

Degueldre, Claude; Cloet, Veerle

2016-11-01

The focus of this work is to evaluate the colloid nature, concentration and size distribution in the pore water of Opalinus Clay and other sedimentary host rocks identified for a potential radioactive waste repository in Switzerland. Because colloids could not be measured in representative undisturbed porewater of these host rocks, predictive modelling based on data from field and laboratory studies is applied. This approach allowed estimating the nature, concentration and size distributions of the colloids in the pore water of these host rocks. As a result of field campaigns, groundwater colloid concentrations are investigated on the basis of their size distribution quantified experimentally using single particle counting techniques. The colloid properties are estimated considering data gained from analogue hydrogeochemical systems ranging from mylonite features in crystalline fissures to sedimentary formations. The colloid concentrations were analysed as a function of the alkaline and alkaline earth element concentrations. Laboratory batch results on clay colloid generation from compacted pellets in quasi-stagnant water are also reported. Experiments with colloids in batch containers indicate that the size distribution of a colloidal suspension evolves toward a common particle size distribution independently of initial conditions. The final suspension size distribution was found to be a function of the attachment factor of the colloids. Finally, calculations were performed using a novel colloid distribution model based on colloid generation, aggregation and sedimentation rates to predict under in-situ conditions what makes colloid concentrations and size distributions batch- or fracture-size dependent. The data presented so far are compared with the field and laboratory data. The colloid occurrence, stability and mobility have been evaluated for the water of the considered potential host rocks. In the pore water of the considered sedimentary host rocks, the clay colloid concentration is expected to be very low (<1ppb, for 10-100nm) which restricts their relevance for radionuclide transport. Copyright © 2016. Published by Elsevier B.V.

Development of Animal Models Against Emerging Coronaviruses: From SARS to MERS coronavirus

PubMed Central

Sutton, Troy C; Subbarao, Kanta

2016-01-01

Two novel coronaviruses have emerged to cause severe disease in humans. While bats may be the primary reservoir for both viruses, SARS coronavirus (SARS-CoV) likely crossed into humans from civets in China, and MERS coronavirus (MERS-CoV) has been transmitted from camels in the Middle East. Unlike SARS-CoV that resolved within a year, continued introductions of MERS-CoV present an on-going public health threat. Animal models are needed to evaluate countermeasures against emerging viruses. With SARS-CoV, several animal species were permissive to infection. In contrast, most laboratory animals are refractory or only semi-permissive to infection with MERS-CoV. This host-range restriction is largely determined by sequence heterogeneity in the MERS-CoV receptor. We describe animal models developed to study coronaviruses, with a focus on host-range restriction at the level of the viral receptor and discuss approaches to consider in developing a model to evaluate countermeasures against MERS-CoV. PMID:25791336

Development of animal models against emerging coronaviruses: From SARS to MERS coronavirus.

PubMed

Sutton, Troy C; Subbarao, Kanta

2015-05-01

Two novel coronaviruses have emerged to cause severe disease in humans. While bats may be the primary reservoir for both viruses, SARS coronavirus (SARS-CoV) likely crossed into humans from civets in China, and MERS coronavirus (MERS-CoV) has been transmitted from camels in the Middle East. Unlike SARS-CoV that resolved within a year, continued introductions of MERS-CoV present an on-going public health threat. Animal models are needed to evaluate countermeasures against emerging viruses. With SARS-CoV, several animal species were permissive to infection. In contrast, most laboratory animals are refractory or only semi-permissive to infection with MERS-CoV. This host-range restriction is largely determined by sequence heterogeneity in the MERS-CoV receptor. We describe animal models developed to study coronaviruses, with a focus on host-range restriction at the level of the viral receptor and discuss approaches to consider in developing a model to evaluate countermeasures against MERS-CoV. Copyright © 2015. Published by Elsevier Inc.

Infection with hepatitis C virus depends on TACSTD2, a regulator of claudin-1 and occludin highly downregulated in hepatocellular carcinoma

PubMed Central

Alayli, Farah; Melis, Marta; Kabat, Juraj; Pomerenke, Anna; Altan-Bonnet, Nihal; Zamboni, Fausto; Emerson, Suzanne U.

2018-01-01

Entry of hepatitis C virus (HCV) into hepatocytes is a complex process that involves numerous cellular factors, including the scavenger receptor class B type 1 (SR-B1), the tetraspanin CD81, and the tight junction (TJ) proteins claudin-1 (CLDN1) and occludin (OCLN). Despite expression of all known HCV-entry factors, in vitro models based on hepatoma cell lines do not fully reproduce the in vivo susceptibility of liver cells to primary HCV isolates, implying the existence of additional host factors which are critical for HCV entry and/or replication. Likewise, HCV replication is severely impaired within hepatocellular carcinoma (HCC) tissue in vivo, but the mechanisms responsible for this restriction are presently unknown. Here, we identify tumor-associated calcium signal transducer 2 (TACSTD2), one of the most downregulated genes in primary HCC tissue, as a host factor that interacts with CLDN1 and OCLN and regulates their cellular localization. TACSTD2 gene silencing disrupts the typical linear distribution of CLDN1 and OCLN along the cellular membrane in both hepatoma cells and primary human hepatocytes, recapitulating the pattern observed in vivo in primary HCC tissue. Mechanistic studies suggest that TACSTD2 is involved in the phosphorylation of CLDN1 and OCLN, which is required for their proper cellular localization. Silencing of TACSTD2 dramatically inhibits HCV infection with a pan-genotype effect that occurs at the level of viral entry. Our study identifies TACSTD2 as a novel regulator of two major HCV-entry factors, CLDN1 and OCLN, which is strongly downregulated in malignant hepatocytes. These results provide new insights into the complex process of HCV entry into hepatocytes and may assist in the development of more efficient cellular systems for HCV propagation in vitro. PMID:29538454

Attraction of the cutaneous leishmaniasis vector Nyssomyia neivai (Diptera: Psychodidae) to host odour components in a wind tunnel

PubMed Central

2012-01-01

Background Laboratory studies of host-seeking olfactory behaviour in sandflies have largely been restricted to the American visceral leishmaniasis vector Lutzomyia longipalpis. In comparison, almost nothing is known about the chemical ecology of related species, which transmit American cutaneous leishmaniasis (ACL), due in part to difficulties in raising these insects in the laboratory. Understanding how ACL vectors locate their hosts will be essential to developing new vector control strategies to combat this debilitating disease. Methods This study examined host-odour seeking behaviour of the ACL vector Nyssomyia neivai (Pinto) (=Lutzomyia neivai) using a wind tunnel olfactometer. The primary aim was to determine whether field-collected female N. neivai would respond to host odours in the laboratory, thereby eliminating the need to maintain colonies of these insects for behavioural experiments. Responses to two key host odour components, 1-octen-3-ol and lactic acid, and a commercially-available mosquito lure (BG-Lure™) were assessed and compared relative to an air control. We also tested whether trials could be conducted outside of the normal evening activity period of N. neivai without impacting on fly behaviour, and whether the same flies could be used to assess baseline responses to air without affecting responses to octenol, thereby reducing the number of flies required for experiments. Results Octenol was found to both activate host-seeking behaviour and attract female N. neivai in the wind tunnel, while lactic acid elicited weaker responses of activation and attractiveness under identical conditions. The BG-Lure did not activate or attract N. neivai under test conditions. Further experiments showed that sandfly behaviour in the wind tunnel was not affected by time of day, such that experiments need not be restricted to nocturnal hours. Moreover, using the same flies to measure both baseline responses to air and attraction to test compounds did not affect odour-seeking behaviour. Conclusions The results of this study demonstrate that N. neivai taken from the field are suitable for use in laboratory olfactometer experiments. It is hoped this work will facilitate further research into chemical ecology of this species, and other ACL vectors. PMID:23009099

Attraction of the cutaneous leishmaniasis vector Nyssomyia neivai (Diptera: Psychodidae) to host odour components in a wind tunnel.

PubMed

Pinto, Mara C; Bray, Daniel P; Eiras, Alvaro E; Carvalheira, Henrique P; Puertas, Camila P

2012-09-25

Laboratory studies of host-seeking olfactory behaviour in sandflies have largely been restricted to the American visceral leishmaniasis vector Lutzomyia longipalpis. In comparison, almost nothing is known about the chemical ecology of related species, which transmit American cutaneous leishmaniasis (ACL), due in part to difficulties in raising these insects in the laboratory. Understanding how ACL vectors locate their hosts will be essential to developing new vector control strategies to combat this debilitating disease. This study examined host-odour seeking behaviour of the ACL vector Nyssomyia neivai (Pinto) (=Lutzomyia neivai) using a wind tunnel olfactometer. The primary aim was to determine whether field-collected female N. neivai would respond to host odours in the laboratory, thereby eliminating the need to maintain colonies of these insects for behavioural experiments. Responses to two key host odour components, 1-octen-3-ol and lactic acid, and a commercially-available mosquito lure (BG-Lure™) were assessed and compared relative to an air control. We also tested whether trials could be conducted outside of the normal evening activity period of N. neivai without impacting on fly behaviour, and whether the same flies could be used to assess baseline responses to air without affecting responses to octenol, thereby reducing the number of flies required for experiments. Octenol was found to both activate host-seeking behaviour and attract female N. neivai in the wind tunnel, while lactic acid elicited weaker responses of activation and attractiveness under identical conditions. The BG-Lure did not activate or attract N. neivai under test conditions. Further experiments showed that sandfly behaviour in the wind tunnel was not affected by time of day, such that experiments need not be restricted to nocturnal hours. Moreover, using the same flies to measure both baseline responses to air and attraction to test compounds did not affect odour-seeking behaviour. The results of this study demonstrate that N. neivai taken from the field are suitable for use in laboratory olfactometer experiments. It is hoped this work will facilitate further research into chemical ecology of this species, and other ACL vectors.

Phylogenetics of Australasian gall flies (Diptera: Fergusoninidae): Evolutionary patterns of host-shifting and gall morphology.

PubMed

Scheffer, S J; Davies, K A; Taylor, G S; Thornhill, A H; Lewis, M L; Winkler, I S; Yeates, D K; Purcell, M F; Makinson, J; Giblin-Davis, R M

2017-10-01

This study investigated host-specificity and phylogenetic relationships in Australian galling flies, Fergusonina Malloch (Diptera: Fergusoninidae), in order to assess diversity and explore the evolutionary history of host plant affiliation and gall morphology. A DNA barcoding approach using COI data from 203 Fergusonina specimens from 5gall types on 56 host plant species indicated 85 presumptive fly species. These exhibited a high degree of host specificity; of the 40 species with multiple representatives, each fed only on a single host genus, 29 (72.5%) were strictly monophagous, and 11 (27.5%) were reared from multiple closely related hosts. COI variation within species was not correlated with either sample size or geographic distance. However variation was greater within oligophagous species, consistent with expectations of the initial stages of host-associated divergence during speciation. Phylogenetic analysis using both nuclear and mitochondrial genes revealed host genus-restricted clades but also clear evidence of multiple colonizations of both host plant genus and host species. With the exception of unilocular peagalls, evolution of gall type was somewhat constrained, but to a lesser degree than host plant association. Unilocular peagalls arose more often than any other gall type, were primarily located at the tips of the phylogeny, and did not form clades comprising more than a few species. For ecological reasons, species of this gall type are predicted to harbor substantially less genetic variation than others, possibly reducing evolutionary flexibility resulting in reduced diversification in unilocular gallers. Published by Elsevier Inc.

Familial Associations of Intense Preoccupations, an Empirical Factor of the Restricted, Repetitive Behaviors and Interests Domain of Autism

ERIC Educational Resources Information Center

Smith, Christopher J.; Lang, Colleen M.; Kryzak, Lauren; Reichenberg, Abraham; Hollander, Eric; Silverman, Jeremy M.

2009-01-01

Background: Clinical heterogeneity of autism likely hinders efforts to find genes associated with this complex psychiatric disorder. Some studies have produced promising results by restricting the sample according to the expression of specific familial factors or components of autism. Previous factor analyses of the restricted, repetitive…

Host Status of Five Weed Species and Their Effects on Pratylenchus zeae Infestation of Maize.

PubMed

Jordaan, E M; De Waele, D

1988-10-01

The host suitability of five of the most common weed species occurring in maize (Zea mays L.) fields in South Africa to Pratylenchus zeae was tested. Based on the number of nematodes per root unit, mealie crotalaria (Crotalaria sphaerocarpa) was a good host; goose grass (Eleusine indica), common pigweed (Amaranthus hybridus), and thorn apple (Datura stramonium) were moderate hosts; and khaki weed (Tagetes minuta) was a poor host. Only the root residues of khaki weed suppressed the P. zeae infestation of subsequently grown maize. When goose grass, khaki weed, and mealie crotalaria were grown in association with maize in soil infested with P. zeae, goose grass and khaki weed severely suppressed maize root development; this resulted in a low number of nematodes per maize root system and a high number of nematodes per maize root unit. Mealie crotalaria did not restrict maize root growth and did not affect nematode densities per maize root system or maize root unit. Special attention should be given to the control of mealie crotalaria, which is a good host for P. zeae, and goose grass, which, in addition to its ability to compete with maize, is also a suitable host for P. zeae.

Host Status of Five Weed Species and Their Effects on Pratylenchus zeae Infestation of Maize

PubMed Central

Jordaan, Elizabeth M.; De Waele, D.

1988-01-01

The host suitability of five of the most common weed species occurring in maize (Zea mays L.) fields in South Africa to Pratylenchus zeae was tested. Based on the number of nematodes per root unit, mealie crotalaria (Crotalaria sphaerocarpa) was a good host; goose grass (Eleusine indica), common pigweed (Amaranthus hybridus), and thorn apple (Datura stramonium) were moderate hosts; and khaki weed (Tagetes minuta) was a poor host. Only the root residues of khaki weed suppressed the P. zeae infestation of subsequently grown maize. When goose grass, khaki weed, and mealie crotalaria were grown in association with maize in soil infested with P. zeae, goose grass and khaki weed severely suppressed maize root development; this resulted in a low number of nematodes per maize root system and a high number of nematodes per maize root unit. Mealie crotalaria did not restrict maize root growth and did not affect nematode densities per maize root system or maize root unit. Special attention should be given to the control of mealie crotalaria, which is a good host for P. zeae, and goose grass, which, in addition to its ability to compete with maize, is also a suitable host for P. zeae. PMID:19290263

Clinical Features and Treatment of Ocular Toxoplasmosis

PubMed Central

Park, Young-Hoon

2013-01-01

Ocular toxoplasmosis is a disease caused by the infection with Toxoplasma gondii through congenital or acquired routes. Once the parasite reaches the retina, it proliferates within host cells followed by rupture of the host cells and invasion into neighboring cells to make primary lesions. Sometimes the restricted parasite by the host immunity in the first scar is activated to infect another lesion nearby the scar. Blurred vision is the main complaint of ocular toxoplasmic patients and can be diagnosed by detection of antibodies or parasite DNA. Ocular toxoplasmosis needs therapy with several combinations of drugs to eliminate the parasite and accompanying inflammation; if not treated it sometimes leads to loss of vision. We describe here clinical features and currently available chemotherapy of ocular toxoplasmosis. PMID:24039281

Clinical features and treatment of ocular toxoplasmosis.

PubMed

Park, Young-Hoon; Nam, Ho-Woo

2013-08-01

Ocular toxoplasmosis is a disease caused by the infection with Toxoplasma gondii through congenital or acquired routes. Once the parasite reaches the retina, it proliferates within host cells followed by rupture of the host cells and invasion into neighboring cells to make primary lesions. Sometimes the restricted parasite by the host immunity in the first scar is activated to infect another lesion nearby the scar. Blurred vision is the main complaint of ocular toxoplasmic patients and can be diagnosed by detection of antibodies or parasite DNA. Ocular toxoplasmosis needs therapy with several combinations of drugs to eliminate the parasite and accompanying inflammation; if not treated it sometimes leads to loss of vision. We describe here clinical features and currently available chemotherapy of ocular toxoplasmosis.

Experimental Adaptation of Burkholderia cenocepacia to Onion Medium Reduces Host Range ▿ † ‡

PubMed Central

Ellis, Crystal N.; Cooper, Vaughn S.

2010-01-01

It is unclear whether adaptation to a new host typically broadens or compromises host range, yet the answer bears on the fate of emergent pathogens and symbionts. We investigated this dynamic using a soil isolate of Burkholderia cenocepacia, a species that normally inhabits the rhizosphere, is related to the onion pathogen B. cepacia, and can infect the lungs of cystic fibrosis patients. We hypothesized that adaptation of B. cenocepacia to a novel host would compromise fitness and virulence in alternative hosts. We modeled adaptation to a specific host by experimentally evolving 12 populations of B. cenocepacia in liquid medium composed of macerated onion tissue for 1,000 generations. The mean fitness of all populations increased by 78% relative to the ancestor, but significant variation among lines was observed. Populations also varied in several phenotypes related to host association, including motility, biofilm formation, and quorum-sensing function. Together, these results suggest that each population adapted by fixing different sets of adaptive mutations. However, this adaptation was consistently accompanied by a loss of pathogenicity to the nematode Caenorhabditis elegans; by 500 generations most populations became unable to kill nematodes. In conclusion, we observed a narrowing of host range as a consequence of prolonged adaptation to an environment simulating a specific host, and we suggest that emergent pathogens may face similar consequences if they become host-restricted. PMID:20154121

Intersections between immune responses and morphological regulation in plants.

PubMed

Uchida, Naoyuki; Tasaka, Masao

2010-06-01

Successful plant pathogens have developed strategies to interfere with the defence mechanisms of their host plants through evolution. Conversely, host plants have evolved systems to counteract pathogen attack. Some pathogens induce pathogenic symptoms on plants that include morphological changes in addition to interference with plant growth. Recent studies, based on molecular biology and genetics using Arabidopsis thaliana, have revealed that factors derived from pathogens can modulate host systems and/or host factors that play important roles in the morphological regulation of host plants. Other reports, meanwhile, have shown that factors known to have roles in plant morphology also function in plant immune responses. Evolutionary conservation of these factors and systems implies that host-pathogen interactions and the evolution they drive have yielded tight links between morphological processes and immune responses. In this review, recent findings about these topics are introduced and discussed.

Looking within the zebrafish to understand the tuberculous granuloma.

PubMed

Ramakrishnan, Lalita

2013-01-01

Tuberculosis is characterized by the formation of complex immune cell aggregates called granulomas, which for nearly a century have been viewed as critical host-beneficial structures to restrict bacterial growth and spread. A different view has now emerged from real-time visualization of granuloma formation and its consequences in the optically transparent and genetically tractable zebrafish larva. Pathogenic mycobacteria have developed mechanisms to use host granulomas for their expansion and dissemination, at least during the innate phases of infection. Host processes that are intended to be beneficial-death of infected macrophages and their subsequent phagocytosis by macrophages that are newly recruited to the growing granuloma-are harnessed by mycobacteria for their own benefit. Mycobacteria can also render the granuloma a safe-haven in the more advanced stages of infection. An understanding of the host and bacterial pathways involved in tuberculous granuloma formation may suggest new ways to combat mycobacterial infection.

What Limits the Distribution of Liriomyza huidobrensis and Its Congener Liriomyza sativae in Their Native Niche: When Temperature and Competition Affect Species' Distribution Range in Guatemala.

PubMed

Rodríguez-Castañeda, G; MacVean, C; Cardona, C; Hof, A R

2017-07-01

Factors limiting distribution range for most species are generally unknown regardless of whether they are native or invasive. We studied factors that could enable or restrict the distribution of two cosmopolitan invasive leafminer fly species, Liriomyza huidobrensis (Blanchard) and Liriomyza sativae (Blanchard) in their native niche. In order to test which ecological and environmental factors affect leafminer distribution we conducted thermal tolerance assays, sampled along elevation gradients and modeled species distribution. Findings from the field and rearing chambers showed a physiological restriction due to high temperatures for L. huidobrensis at 28-29 °C, above which adult emergence is compromised. We also found that maximum temperatures below 22 °C, typical of tropical highlands, favored L. huidobrensis. L. sativae was found across a wider temperature range (i.e., from 21 to 36 °C) in Guatemala. Our finding of a physiological threshold in temperature for L. huidobrensis may enable us to predict its invasive risk when combined with the environmental conditions at horticultural ports of entry and the global agricultural landscape. Further, it strengthens our predictions on shifts in distribution of the leafminer fly under future climate. We also found a temperature mediated competitive exclusion interaction between the two herbivore species, where L. sativae occurred at temperatures < 22 °C only in the absence of L. huidobrensis. We show that parasitoids had a negative effect on the leafminer flies, which varied with host plant. Finally, we show the importance of taking a multiaspect approach when investigating what limits distribution and invasiveness of a species. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America.

Evolutionary genomics and HIV restriction factors.

PubMed

Pyndiah, Nitisha; Telenti, Amalio; Rausell, Antonio

2015-03-01

To provide updated insights into innate antiviral immunity and highlight prototypical evolutionary features of well characterized HIV restriction factors. Recently, a new HIV restriction factor, Myxovirus resistance 2, has been discovered and the region/residue responsible for its activity identified using an evolutionary approach. Furthermore, IFI16, an innate immunity protein known to sense several viruses, has been shown to contribute to the defense to HIV-1 by causing cell death upon sensing HIV-1 DNA. Restriction factors against HIV show characteristic signatures of positive selection. Different patterns of accelerated sequence evolution can distinguish antiviral strategies--offense or defence--as well as the level of specificity of the antiviral properties. Sequence analysis of primate orthologs of restriction factors serves to localize functional domains and sites responsible for antiviral action. We use recent discoveries to illustrate how evolutionary genomic analyses help identify new antiviral genes and their mechanisms of action.

Establishment of the onset of host specificity in four phyllobothriid tapeworm species (Cestoda: Tetraphyllidea) using a molecular approach.

PubMed

Randhawa, H S; Saunders, G W; Burt, M D B

2007-08-01

A parasitological survey in the Bay of Fundy, Canada, resulted in the recovery of mature specimens from 5 species of phyllobothriid tapeworms (Cestoda: Tetraphyllidea) from 4 rajid skates: Echeneibothrium canadensis and E. dubium abyssorum specimens from Amblyraja radiata; E. vernetae and Pseudanthobothrium n.sp. from Leucoraja erinacea and L. ocellata; and P. hanseni from A. radiata and Malacoraja senta. Partial sequence data of a variable region (D2) from the large subunit ribosomal DNA (LSU) were used here to determine the host distribution of immature specimens for 4 of these 5 species (E. d. abyssorum was not included in the analyses). Immature specimens from both Pseudanthobothrium spp. were identified in the same hosts as recorded previously for mature specimens, thus suggesting that there are mechanisms that prevent the attachment of the parasite in an 'unsuitable' host species. Immature E. canadensis specimens were recovered exclusively from A. radiata, whereas immature E. vernetae specimens were recovered from L. erinacea and A. radiata, despite the latter host species not harbouring mature E. vernetae specimens. Their presence in the latter host species may be explained by host restriction or resistance, which allows the attachment of the parasites in the 'wrong' host species, but not establishment or development.

Human Urinary Composition Controls Antibacterial Activity of Siderocalin* ♦

PubMed Central

Shields-Cutler, Robin R.; Crowley, Jan R.; Hung, Chia S.; Stapleton, Ann E.; Aldrich, Courtney C.; Marschall, Jonas; Henderson, Jeffrey P.

2015-01-01

During Escherichia coli urinary tract infections, cells in the human urinary tract release the antimicrobial protein siderocalin (SCN; also known as lipocalin 2, neutrophil gelatinase-associated lipocalin/NGAL, or 24p3). SCN can interfere with E. coli iron acquisition by sequestering ferric iron complexes with enterobactin, the conserved E. coli siderophore. Here, we find that human urinary constituents can reverse this relationship, instead making enterobactin critical for overcoming SCN-mediated growth restriction. Urinary control of SCN activity exhibits wide ranging individual differences. We used these differences to identify elevated urinary pH and aryl metabolites as key biochemical host factors controlling urinary SCN activity. These aryl metabolites are well known products of intestinal microbial metabolism. Together, these results identify an innate antibacterial immune interaction that is critically dependent upon individualistic chemical features of human urine. PMID:25861985

Consequences of genomic diversity in Mycobacterium tuberculosis

PubMed Central

Coscolla, Mireia; Gagneux, Sebastien

2014-01-01

The causative agent of human tuberculosis, Mycobacterium tuberculosis complex (MTBC), comprises seven phylogenetically distinct lineages associated with different geographical regions. Here we review the latest findings on the nature and amount of genomic diversity within and between MTBC lineages. We then review recent evidence for the effect of this genomic diversity on mycobacterial phenotypes measured experimentally and in clinical settings. We conclude that overall, the most geographically widespread Lineage 2 (includes Beijing) and Lineage 4 (also known as Euro-American) are more virulent than other lineages that are more geographically restricted. This increased virulence is associated with delayed or reduced pro-inflammatory host immune responses, greater severity of disease, and enhanced transmission. Future work should focus on the interaction between MTBC and human genetic diversity, as well as on the environmental factors that modulate these interactions. PMID:25453224

Expression of von Willebrand factor and caldesmon in the placental tissues of pregnancies complicated with intrauterine growth restriction.

PubMed

Göksever Çelik, Hale; Uhri, Mehmet; Yildirim, Gökhan

2017-11-02

The decreased placental perfusion is the underlying reason for intrauterine growth restriction that in turn leads to reduced placental perfusion and ischemia. However, there are several issues to be understood in the pathophysiology of intrauterine growth restriction. We aimed to study whether any compensatory response in placental vascular bed occur in pregnancies complicated with intrauterine growth restriction by the immunohistochemical staining of von Willebrand factor and caldesmon in placental tissues. A total of 103 pregnant women was enrolled in the study including 50 patients who were complicated with IUGR and 50 uncomplicated control patients. The study was designed in a prospective manner. All placentas were also stained with von Willebrand factor and caldesmon monoclonal kits. The immunohistochemical staining of von Willebrand factor and caldesmon expressions in placental tissues were different between normal and intrauterine growth restriction group. The percentages of 2+ and 3+ von Willebrand factor expression were higher in the intrauterine growth restriction group comparing with the normal group, although the difference was not statistically significant. The intensity of caldesmon expression was significantly lower in the intrauterine growth restriction group in comparison with the normal group (p < .001). Angiogenesis occurs as a placental response to intrauterine growth restriction which is a hypoxic condition. But newly formed vessels are immature and not strong enough. Our study is important to clarify the pathophysiology and placental compensatory responses in intrauterine growth restriction.

The family context of low-income parents who restrict child screen time.

PubMed

Lampard, Amy M; Jurkowski, Janine M; Davison, Kirsten K

2013-10-01

The American Academy of Pediatrics recommends that parents restrict child screen time to two hours per day, but many preschool-aged children exceed this viewing recommendation. Modifying children's viewing habits will require collaborating with parents, but little is known about the factors that influence parents' capacity for effective screen-related parenting. This study aimed to identify the demographic, family and community contextual factors associated with low-income parents' restriction of child screen time. Parents (N=146) of children (age 2-5 years) attending Head Start centers in the United States completed a self-report survey in 2010 assessing parent and child screen use (television, DVD, video, video games, and leisure-time computer use), parent restriction of child screen time, and family (parent stress, social support, and life pressures) and community (neighborhood safety and social capital) factors. Children were more likely to meet the American Academy of Pediatrics screen time recommendation if their parent reported high restriction of child screen time. Parent and child demographic characteristics were not associated with parents' restriction of child screen time. In multivariate analysis, less parent screen time, fewer parent life pressures, and greater social support were associated with parents' high restriction of screen time. Family contextual factors may play an important role in enabling low-income parents to restrict their children's screen time. When counseling low-income parents about the importance of restricting child screen time, practitioners should be sensitive to family contextual factors that may influence parents' capacity to implement this behavior change.

48 CFR 236.602-70 - Restriction on award of overseas architect-engineer contracts to foreign firms.

Code of Federal Regulations, 2011 CFR

2011-10-01

... countries bordering the Arabian Gulf, shall be awarded only to United States firms or to joint ventures of United States and host nation firms. [62 FR 2858, Jan. 17, 1997, as amended at 76 FR 58155, Sept. 20...

48 CFR 236.602-70 - Restriction on award of overseas architect-engineer contracts to foreign firms.

Code of Federal Regulations, 2012 CFR

2012-10-01

... countries bordering the Arabian Gulf, shall be awarded only to United States firms or to joint ventures of United States and host nation firms. [62 FR 2858, Jan. 17, 1997, as amended at 76 FR 58155, Sept. 20...

48 CFR 236.602-70 - Restriction on award of overseas architect-engineer contracts to foreign firms.

Code of Federal Regulations, 2013 CFR

2013-10-01

... countries bordering the Arabian Gulf, shall be awarded only to United States firms or to joint ventures of United States and host nation firms. [62 FR 2858, Jan. 17, 1997, as amended at 76 FR 58155, Sept. 20...

Weed hosts Globodera pallida from Idaho

USDA-ARS?s Scientific Manuscript database

The potato cyst nematode, Globodera pallida (PCN), a restricted pest in the USA, was first reported in Bingham and Bonneville counties of Idaho in 2006. The US government and Idaho State Department of Agriculture hope to eradicate it from infested fields. Eradicating PCN will require depriving the n...

Does the Host Contribute to Modulation of Mycotoxin Production by Fruit Pathogens?

PubMed Central

Kumar, Dilip; Barad, Shiri; Sionov, Edward; Prusky, Dov B.

2017-01-01

Storage of freshly harvested fruit is a key factor in modulating their supply for several months after harvest; however, their quality can be reduced by pathogen attack. Fruit pathogens may infect their host through damaged surfaces, such as mechanical injuries occurring during growing, harvesting, and packing, leading to increased colonization as the fruit ripens. Of particular concern are fungal pathogens that not only macerate the host tissue but also secrete significant amounts of mycotoxins. Many studies have described the importance of physiological factors, including stage of fruit development, biochemical factors (ripening, C and N content), and environmental factors (humidity, temperature, water deficit) on the occurrence of mycotoxins. However, those factors usually show a correlative effect on fungal growth and mycotoxin accumulation. Recent reports have suggested that host factors can induce fungal metabolism, leading to the synthesis and accumulation of mycotoxins. This review describes the new vision of host-factor impact on the regulation of mycotoxin biosynthetic gene clusters underlying the complex regulation of mycotoxin accumulation in ripening fruit. PMID:28895896

Tumour-associated and non-tumour-associated microbiota in colorectal cancer

PubMed Central

Flemer, Burkhardt; Lynch, Denise B; Brown, Jillian M R; Jeffery, Ian B; Ryan, Feargal J; Claesson, Marcus J; O'Riordain, Micheal; Shanahan, Fergus; O'Toole, Paul W

2017-01-01

Objective A signature that unifies the colorectal cancer (CRC) microbiota across multiple studies has not been identified. In addition to methodological variance, heterogeneity may be caused by both microbial and host response differences, which was addressed in this study. Design We prospectively studied the colonic microbiota and the expression of specific host response genes using faecal and mucosal samples (‘ON’ and ‘OFF’ the tumour, proximal and distal) from 59 patients undergoing surgery for CRC, 21 individuals with polyps and 56 healthy controls. Microbiota composition was determined by 16S rRNA amplicon sequencing; expression of host genes involved in CRC progression and immune response was quantified by real-time quantitative PCR. Results The microbiota of patients with CRC differed from that of controls, but alterations were not restricted to the cancerous tissue. Differences between distal and proximal cancers were detected and faecal microbiota only partially reflected mucosal microbiota in CRC. Patients with CRC can be stratified based on higher level structures of mucosal-associated bacterial co-abundance groups (CAGs) that resemble the previously formulated concept of enterotypes. Of these, Bacteroidetes Cluster 1 and Firmicutes Cluster 1 were in decreased abundance in CRC mucosa, whereas Bacteroidetes Cluster 2, Firmicutes Cluster 2, Pathogen Cluster and Prevotella Cluster showed increased abundance in CRC mucosa. CRC-associated CAGs were differentially correlated with the expression of host immunoinflammatory response genes. Conclusions CRC-associated microbiota profiles differ from those in healthy subjects and are linked with distinct mucosal gene-expression profiles. Compositional alterations in the microbiota are not restricted to cancerous tissue and differ between distal and proximal cancers. PMID:26992426

The host-interacting proteins Tp0750 and Pallilysin; conservation among treponemes and restriction of proteolytic capacity to Treponema pallidum

USDA-ARS?s Scientific Manuscript database

The spirochete Treponema pallidum is the causative agent of syphilis, a chronic, sexually transmitted bacterial infection characterized by multiple symptomatic and asymptomatic stages. Treponema pallidum is significantly more invasive than other treponemal species, being able to cross both the blood...

76 FR 52541 - Asian Longhorned Beetle; Quarantined Areas and Regulated Articles

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-23

.... APHIS-2010-0128] Asian Longhorned Beetle; Quarantined Areas and Regulated Articles AGENCY: Animal and... interstate movement of regulated articles from those areas will be restricted. We are also updating the list of regulated articles in order to reflect new information concerning host plants. These actions are...

75 FR 34320 - Asian Longhorned Beetle; Quarantined Area and Regulated Articles

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-17

.... APHIS-2010-0004] Asian Longhorned Beetle; Quarantined Area and Regulated Articles AGENCY: Animal and... of quarantined areas and restricting the interstate movement of regulated articles from that area. We are also updating the list of regulated articles in order to reflect new information concerning host...

Horizontal gene acquisitions, mobile element proliferation, and genome decay in the host-restricted plant pathogen erwinia tracheiphila

USDA-ARS?s Scientific Manuscript database

Modern industrial agriculture depends on high-density cultivation of genetically similar crop plants, creating favorable conditions for the emergence of novel pathogens with increased fitness in managed compared with ecologically intact settings. Here, we present the genome sequence of six strains o...

Novel, host-restricted genotypes of Bordetella bronchiseptica associated with phocine respiratory tract isolates

USDA-ARS?s Scientific Manuscript database

Bordetella bronchiseptica is a widespread respiratory pathogen in a variety of wild and domesticated animals. During a succession of phocine morbillivirus outbreaks occurring over the past 25 years, it was identified as a frequent secondary invader, often believed to be the cause of death. Prior a...

Contribution of host, bacterial factors and antibiotic treatment to mortality in adult patients with bacteraemic pneumococcal pneumonia.

PubMed

Naucler, Pontus; Darenberg, Jessica; Morfeldt, Eva; Ortqvist, Ake; Henriques Normark, Birgitta

2013-06-01

Host and bacterial factors as well as different treatment regimens are likely to influence the outcome in patients with bacteraemic pneumococcal pneumonia. To estimate the relative contribution of host factors as well as bacterial factors and antibiotic treatment to mortality in bacteraemic pneumococcal pneumonia. A cohort study of 1580 adult patients with community-acquired bacteraemic pneumococcal pneumonia was conducted between 2007 and 2009 in Sweden. Data on host factors and initial antibiotic treatment were collected from patient records. Antibiotic resistance and serotype were determined for bacterial isolates. Logistic regression analyses were performed to assess risk factors for 30-day mortality. Smoking, alcohol abuse, solid tumour, liver disease and renal disease attributed to 14.9%, 13.1%, 13.1%, 8.0% and 7.4% of the mortality, respectively. Age was the strongest predictor, and mortality increased exponentially from 1.3% in patients <45 years of age to 26.1% in patients aged ≥85 years. There was considerable confounding by host factors on the association between serotype and mortality. Increasing age, liver disease and serotype were associated with mortality in patients admitted to the ICU. Combined treatment with β-lactam antibiotics and macrolide/quinolone was associated with reduced mortality in patients in the ICU, although confounding could not be ruled out. Host factors appear to be more important than the specific serotype as determinants of mortality in patients with bacteraemic pneumococcal pneumonia. Several host factors were identified that contribute to mortality, which is important for prognosis and to guide targeted prevention strategies.

Using host-pathogen protein interactions to identify and characterize Francisella tularensis virulence factors.

PubMed

Wallqvist, Anders; Memišević, Vesna; Zavaljevski, Nela; Pieper, Rembert; Rajagopala, Seesandra V; Kwon, Keehwan; Yu, Chenggang; Hoover, Timothy A; Reifman, Jaques

2015-12-29

Francisella tularensis is a select bio-threat agent and one of the most virulent intracellular pathogens known, requiring just a few organisms to establish an infection. Although several virulence factors are known, we lack an understanding of virulence factors that act through host-pathogen protein interactions to promote infection. To address these issues in the highly infectious F. tularensis subsp. tularensis Schu S4 strain, we deployed a combined in silico, in vitro, and in vivo analysis to identify virulence factors and their interactions with host proteins to characterize bacterial infection mechanisms. We initially used comparative genomics and literature to identify and select a set of 49 putative and known virulence factors for analysis. Each protein was then subjected to proteome-scale yeast two-hybrid (Y2H) screens with human and murine cDNA libraries to identify potential host-pathogen protein-protein interactions. Based on the bacterial protein interaction profile with both hosts, we selected seven novel putative virulence factors for mutant construction and animal validation experiments. We were able to create five transposon insertion mutants and used them in an intranasal BALB/c mouse challenge model to establish 50 % lethal dose estimates. Three of these, ΔFTT0482c, ΔFTT1538c, and ΔFTT1597, showed attenuation in lethality and can thus be considered novel F. tularensis virulence factors. The analysis of the accompanying Y2H data identified intracellular protein trafficking between the early endosome to the late endosome as an important component in virulence attenuation for these virulence factors. Furthermore, we also used the Y2H data to investigate host protein binding of two known virulence factors, showing that direct protein binding was a component in the modulation of the inflammatory response via activation of mitogen-activated protein kinases and in the oxidative stress response. Direct interactions with specific host proteins and the ability to influence interactions among host proteins are important components for F. tularensis to avoid host-cell defense mechanisms and successfully establish an infection. Although direct host-pathogen protein-protein binding is only one aspect of Francisella virulence, it is a critical component in directly manipulating and interfering with cellular processes in the host cell.

Proliferation of epithelial cell rests, formation of apical cysts, and regression of apical cysts after periapical wound healing.

PubMed

Lin, Louis M; Huang, George T-J; Rosenberg, Paul A

2007-08-01

There is continuing controversy regarding the potential for inflammatory apical cysts to heal after nonsurgical endodontic therapy. Molecular cell biology may provide answers to a series of related questions. How are the epithelial cell rests of Malassez stimulated to proliferate? How are the apical cysts formed? How does the lining epithelium of apical cysts regress after endodontic therapy? Epithelial cell rests are induced to divide and proliferate by inflammatory mediators, proinflammatory cytokines, and growth factors released from host cells during periradicular inflammation. Quiescent epithelial cell rests can behave like restricted-potential stem cells if stimulated to proliferate. Formation of apical cysts is most likely caused by the merging of proliferating epithelial strands from all directions to form a three-dimensional ball mass. After endodontic therapy, epithelial cells in epithelial strands of periapical granulomas and the lining epithelium of apical cysts may stop proliferating because of a reduction in inflammatory mediators, proinflammatory cytokines, and growth factors. Epithelial cells will also regress because of activation of apoptosis or programmed cell death through deprivation of survival factors or by receiving death signals during periapical wound healing.

Structure of the Epiphyte Community in a Tropical Montane Forest in SW China

PubMed Central

Zhao, Mingxu; Geekiyanage, Nalaka; Xu, Jianchu; Khin, Myo Myo; Nurdiana, Dian Ridwan; Paudel, Ekananda; Harrison, Rhett Daniel

2015-01-01

Vascular epiphytes are an understudied and particularly important component of tropical forest ecosystems. However, owing to the difficulties of access, little is known about the properties of epiphyte-host tree communities and the factors structuring them, especially in Asia. We investigated factors structuring the vascular epiphyte-host community and its network properties in a tropical montane forest in Xishuangbanna, SW China. Vascular epiphytes were surveyed in six plots located in mature forests. Six host and four micro-site environmental factors were investigated. Epiphyte diversity was strongly correlated with host size (DBH, diameter at breast height), while within hosts the highest epiphyte diversity was in the middle canopy and epiphyte diversity was significantly higher in sites with canopy soil or a moss mat than on bare bark. DBH, elevation and stem height explained 22% of the total variation in the epiphyte species assemblage among hosts, and DBH was the most important factor which alone explained 6% of the variation. Within hosts, 51% of the variation in epiphyte assemblage composition was explained by canopy position and substrate, and the most important single factor was substrate which accounted for 16% of the variation. Analysis of network properties indicated that the epiphyte host community was highly nested, with a low level of epiphyte specialization, and an almost even interaction strength between epiphytes and host trees. Together, these results indicate that large trees harbor a substantial proportion of the epiphyte community in this forest. PMID:25856457

Hypoxia promotes Mycobacterium tuberculosis-specific up-regulation of granulysin in human T cells.

PubMed

Zenk, Sebastian F; Vollmer, Michael; Schercher, Esra; Kallert, Stephanie; Kubis, Jan; Stenger, Steffen

2016-06-01

Oxygen tension affects local immune responses in inflammation and infection. In tuberculosis mycobacteria avoid hypoxic areas and preferentially persist and reactivate in the oxygen-rich apex of the lung. Oxygen restriction activates antimicrobial effector mechanisms in macrophages and restricts growth of intracellular Mycobacterium tuberculosis (M.Tb). The effect of oxygen restriction on T cell-mediated antimicrobial effector mechanisms is unknown. Therefore we determined the influence of hypoxia on the expression of granulysin, an antimicrobial peptide of lymphocytes. Hypoxia increased the antigen-specific up-regulation of granulysin mRNA and protein in human CD4(+) and CD8(+) T lymphocytes. This observation was functionally relevant, because oxygen restriction supported the growth-limiting effect of antigen-specific T cells against virulent M.Tb residing in primary human macrophages. Our results provide evidence that oxygen restriction promotes the expression of granulysin and suggest that this effect-in conjunction with additional T cell-mediated immune responses-supports protection against mycobacteria. The therapeutic modulation of oxygen availability may offer a new strategy for the host-directed therapy of infectious diseases with intracellular pathogens.

A revision of Plasmopara penniseti, with implications for the host range of the downy mildews with pyriform haustoria.

PubMed

Thines, Marco; Göker, Markus; Oberwinkler, Franz; Spring, Otmar

2007-12-01

Plasmopara penniseti is the sole member of the genus Plasmopara parasitic to Poaceae, after the genus Viennotia had been described to accommodate Plasmopara oplismeni. Morphological, ultrastructural, and molecular phylogenetic data indicate that Plasmopara penniseti is not closely related to the generic type, and it is, therefore, transferred to the newly described genus Poakatesthia. The view that the genera of downy mildews with pyriform to vesicular haustoria (Basidiophora, Benua, Bremia, Paraperonospora, Plasmopara, Plasmoverna, and Protobremia) include species parasitic to Poaceae has to be discarded. All of these genera are apparently restricted to dicotyledonous hosts.

Resolving the infection process reveals striking differences in the contribution of environment, genetics and phylogeny to host-parasite interactions.

PubMed

Duneau, David; Luijckx, Pepijn; Ben-Ami, Frida; Laforsch, Christian; Ebert, Dieter

2011-02-22

Infection processes consist of a sequence of steps, each critical for the interaction between host and parasite. Studies of host-parasite interactions rarely take into account the fact that different steps might be influenced by different factors and might, therefore, make different contributions to shaping coevolution. We designed a new method using the Daphnia magna - Pasteuria ramosa system, one of the rare examples where coevolution has been documented, in order to resolve the steps of the infection and analyse the factors that influence each of them. Using the transparent Daphnia hosts and fluorescently-labelled spores of the bacterium P. ramosa, we identified a sequence of infection steps: encounter between parasite and host; activation of parasite dormant spores; attachment of spores to the host; and parasite proliferation inside the host. The chances of encounter had been shown to depend on host genotype and environment. We tested the role of genetic and environmental factors in the newly described activation and attachment steps. Hosts of different genotypes, gender and species were all able to activate endospores of all parasite clones tested in different environments; suggesting that the activation cue is phylogenetically conserved. We next established that parasite attachment occurs onto the host oesophagus independently of host species, gender and environmental conditions. In contrast to spore activation, attachment depended strongly on the combination of host and parasite genotypes. Our results show that different steps are influenced by different factors. Host-type-independent spore activation suggests that this step can be ruled out as a major factor in Daphnia-Pasteuria coevolution. On the other hand, we show that the attachment step is crucial for the pronounced genetic specificities of this system. We suggest that this one step can explain host population structure and could be a key force behind coevolutionary cycles. We discuss how different steps can explain different aspects of the coevolutionary dynamics of the system: the properties of the attachment step, explaining the rapid evolution of infectivity and the properties of later parasite proliferation explaining the evolution of virulence. Our study underlines the importance of resolving the infection process in order to better understand host-parasite interactions.

Arabidopsis thaliana is a susceptible host plant for the holoparasite Cuscuta spec.

PubMed

Birschwilks, Mandy; Sauer, Norbert; Scheel, Dierk; Neumann, Stefanie

2007-10-01

Arabidopsis thaliana and Cuscuta spec. represent a compatible host-parasite combination. Cuscuta produces a haustorium that penetrates the host tissue. In early stages of development the searching hyphae on the tip of the haustorial cone are connected to the host tissue by interspecific plasmodesmata. Ten days after infection, translocation of the fluorescent dyes, Texas Red (TR) and 5,6-carboxyfluorescein (CF), demonstrates the existence of a continuous connection between xylem and phloem of the host and parasite. Cuscuta becomes the dominant sink in this host-parasite system. Transgenic Arabidopsis plants expressing genes encoding the green fluorescent protein (GFP; 27 kDa) or a GFP-ubiquitin fusion (36 kDa), respectively, under the companion cell (CC)-specific AtSUC2 promoter were used to monitor the transfer of these proteins from the host sieve elements to those of Cuscuta. Although GFP is transferred unimpedly to the parasite, the GFP-ubiquitin fusion could not be detected in Cuscuta. A translocation of the GFP-ubiquitin fusion protein was found to be restricted to the phloem of the host, although a functional symplastic pathway exists between the host and parasite, as demonstrated by the transport of CF. These results indicate a peripheral size exclusion limit (SEL) between 27 and 36 kDa for the symplastic connections between host and Cuscuta sieve elements. Forty-six accessions of A. thaliana covering the entire range of its genetic diversity, as well as Arabidopsis halleri, were found to be susceptible towards Cuscuta reflexa.

Posthodiplostomum cuticola (Digenea: Diplostomatidae) in intermediate fish hosts: factors contributing to the parasite infection and prey selection by the definitive bird host.

PubMed

Ondracková, M; Simková, A; Gelnar, M; Jurajda, P

2004-12-01

Infection parameters of Posthodiplostomum cuticola, a digenean parasite with a complex life-cycle, were investigated in fish (the second intermediate host) from 6 floodplain water bodies over 2 years. A broad range of factors related to abiotic characteristics of localities, density of the first intermediate (planorbid snails) and definitive (wading birds) hosts and fish community structure were tested for their effects on P. cuticola infection in juvenile and adult fish. Characters of the littoral zone and flood duration were found to be important factors for the presence of the first intermediate and definitive hosts. Visitation time of definitive bird hosts was also related to adult fish host density. Localities with P. cuticola infected fish were visited by a higher number of bird species. Infection of P. cuticola in fish and similarities in infection among fish host assemblages were correlated with fish host density and fish species composition. Parasite infection in both adult and juvenile fishes was associated with the slope of the bank and the bottom type, in particular in juvenile fish assemblages with snail host density. We conclude that habitat characteristics, snail host density and fish community structure contribute significantly to P. cuticola infection in fish hosts.

Near-infrared properties of quasar and Seyfert host galaxies

NASA Astrophysics Data System (ADS)

McLeod, Kim Katris

1994-01-01

We present near-infrared images of nearly 100 host galaxies of Active Galactic Nuclei (AGN). Our quasar sample is comprised of the 50 quasars from the Palomar Green Bright Quasar Survey with redshifts z less than or equal to 0.3. We have restricted the redshift range to ensure adequate spatial resolution, galaxy detectability, and minimal distance-dependent effects, while still giving a large sample of objects. For lower-luminosity AGN we have chosen to image the CfA Seyfert sample. This sample is composed of 48 Seyferts, roughly equally divided among types 1, 1.5-1.9, and 2. This sample was spectroscopically selected, and, therefore, is not biased towards Seyferts with significant star formation. Taken together, these samples allow a statistical look at the continuity of host galaxy properties over a factor of 10,000 in nuclear luminosity. We find the near-infrared light to be a good tracer of luminous mass in these galaxies. The Seyferts are found in galaxies of type SO to Sc. The radio quiet quasars live in similar kinds of galaxies spanning the same range of mass centered around L(*). However, for the most luminous quasars, there is a correlation between the minimum host galaxy mass and the luminosity of the active nucleus. Radio-loud quasars are generally found in hosts more massive than an L(*) galaxy. We also detect a population of low mass host galaxies with very low luminosity Seyfert nuclei. The low luminosity quasars and the Seyferts both tend to lie in host galaxies seen preferentially face-on, which suggests there is a substantial amount of obscuration coplanar with the galaxian disk. The obscuration must be geometrically thick (thickness-to-radius approximately 1) and must cover a significant fraction of the narrow line region (r greater than 100 pc). We have examined our images for signs of perturbations that could drive fuel toward the galaxy nucleus, but there are none we can identify at a significant level. The critical element for fueling is evidently not reflected clearly in the large scale distribution of luminous mass in the galaxy. We also present an infrared image of the jet of SC 273 and compare it to optical and radio images from the literature.

Near-Infrared Properties of Quasar and Seyfert Host Galaxies

NASA Astrophysics Data System (ADS)

McLeod, Kim Katris

1995-01-01

We present near-infrared images of nearly 100 host galaxies of Active Galactic Nuclei (AGN). Our quasar sample is comprised of the 50 quasars from the Palomar Green Bright Quasar Survey with redshifts z\\<= 0.3. We have restricted the redshift range to ensure adequate spatial resolution, galaxy detectability, and minimal distance-dependent effects, while still giving a large sample of objects. For lower-luminosity AGN we have chosen to image the CfA Seyfert sample. This sample is composed of 48 Seyferts, roughly equally divided among types 1, 1.5-1.9, and 2. This sample was spectroscopically selected, and, therefore, is not biased towards Seyferts with significant star formation. Taken together, these samples allow a statistical look at the continuity of host-galaxy properties over a factor of 10,000 in nuclear luminosity. We find the near-infrared light to be a good tracer of luminous mass in these galaxies. The Seyferts are found in galaxies of type S0 to Sc. The radio quiet quasars live in similar kinds of galaxies spanning the same range of mass centered around L*. However, for the most luminous quasars, there is a correlation between the minimum host-galaxy mass and the luminosity of the active nucleus. Radio-loud quasars are generally found in hosts more massive than an L* galaxy. We also detect a population of low-mass host galaxies with very low-luminosity Seyfert nuclei. The low luminosity quasars and the Seyferts both tend to lie in host galaxies seen preferentially face-on, which suggests there is a substantial amount of obscuration coplanar with the galaxian disk. The obscuration must be geometrically thick (thickness-to-radius ~1) and must cover a significant fraction of the narrow line region (r>100 pc). We have examined our images for signs of perturbations that could drive fuel toward the galaxy nucleus, but there are none we can identify at a significant level. The critical element for fueling is evidently not reflected clearly in the large scale distribution of luminous mass in the galaxy. We also present an infrared image of the jet of 3C 273 and compare it to visible and radio images from the literature. (SECTION: Dissertation Summaries)

Host specificity and the probability of discovering species of helminth parasites.

PubMed

Poulin, R; Mouillot, D

2005-06-01

Different animal species have different probabilities of being discovered and described by scientists, and these probabilities are determined to a large extent by the biological characteristics of these species. For instance, species with broader geographical ranges are more likely to be encountered by collectors than species with restricted distributions; indeed, the size of the geographical range is often the best predictor of a species' date of description. For parasitic organisms, host specificity may be similarly linked to the probability of a species being found. Here, using data on 170 helminth species parasitic in freshwater fishes, we show that host specificity is associated with the year in which the helminths were described. Helminths that exploit more host species, and to a lesser degree those that exploit a broader taxonomic range of host species, tend to be discovered earlier than the more host-specific helminths. This pattern was observed across all helminth species, as well as within the different helminth taxa (trematodes, cestodes, nematodes and acanthocephalans). Our results demonstrate that the parasite species known at any given point in time are not a random subset of existing species, but rather a biased subset with respect to the parasites' biological properties.

CD8+ TCR repertoire formation is guided primarily by the peptide component of the antigenic complex.

PubMed

Koning, Dan; Costa, Ana I; Hoof, Ilka; Miles, John J; Nanlohy, Nening M; Ladell, Kristin; Matthews, Katherine K; Venturi, Vanessa; Schellens, Ingrid M M; Borghans, Jose A M; Kesmir, Can; Price, David A; van Baarle, Debbie

2013-02-01

CD8(+) T cells recognize infected or dysregulated cells via the clonotypically expressed αβ TCR, which engages Ag in the form of peptide bound to MHC class I (MHC I) on the target cell surface. Previous studies have indicated that a diverse Ag-specific TCR repertoire can be beneficial to the host, yet the determinants of clonotypic diversity are poorly defined. To better understand the factors that govern TCR repertoire formation, we conducted a comprehensive clonotypic analysis of CD8(+) T cell populations directed against epitopes derived from EBV and CMV. Neither pathogen source nor the restricting MHC I molecule were linked with TCR diversity; indeed, both HLA-A and HLA-B molecules were observed to interact with an overlapping repertoire of expressed TRBV genes. Peptide specificity, however, markedly impacted TCR diversity. In addition, distinct peptides sharing HLA restriction and viral origin mobilized TCR repertoires with distinct patterns of TRBV gene usage. Notably, no relationship was observed between immunodominance and TCR diversity. These findings provide new insights into the forces that shape the Ag-specific TCR repertoire in vivo and highlight a determinative role for the peptide component of the peptide-MHC I complex on the molecular frontline of CD8(+) T cell-mediated immune surveillance.

Staphylococcus aureus genomics and the impact of horizontal gene transfer.

PubMed

Lindsay, Jodi A

2014-03-01

Whole genome sequencing and microarrays have revealed the population structure of Staphylococcus aureus, and identified epidemiological shifts, transmission routes, and adaptation of major clones. S. aureus genomes are highly diverse. This is partly due to a population structure of conserved lineages, each with unique combinations of genes encoding surface proteins, regulators, immune evasion and virulence pathways. Even more variable are the mobile genetic elements (MGE), which encode key proteins for antibiotic resistance, virulence and host-adaptation. MGEs can transfer at high frequency between isolates of the same lineage by horizontal gene transfer (HGT). There is increasing evidence that HGT is key to bacterial adaptation and success. Recent studies have shed light on new mechanisms of DNA transfer such as transformation, the identification of receptors for transduction, on integration of DNA pathways, mechanisms blocking transfer including CRISPR and new restriction systems, strategies for evasion of restriction barriers, as well as factors influencing MGE selection and stability. These studies have also lead to new tools enabling construction of genetically modified clinical S. aureus isolates. This review will focus on HGT mechanisms and their importance in shaping the evolution of new clones adapted to antibiotic resistance, healthcare, communities and livestock. Copyright © 2013 Elsevier GmbH. All rights reserved.

Common themes in microbial pathogenicity revisited.

PubMed Central

Finlay, B B; Falkow, S

1997-01-01

Bacterial pathogens employ a number of genetic strategies to cause infection and, occasionally, disease in their hosts. Many of these virulence factors and their regulatory elements can be divided into a smaller number of groups based on the conservation of similar mechanisms. These common themes are found throughout bacterial virulence factors. For example, there are only a few general types of toxins, despite a large number of host targets. Similarly, there are only a few conserved ways to build the bacterial pilus and nonpilus adhesins used by pathogens to adhere to host substrates. Bacterial entry into host cells (invasion) is a complex mechanism. However, several common invasion themes exist in diverse microorganisms. Similarly, once inside a host cell, pathogens have a limited number of ways to ensure their survival, whether remaining within a host vacuole or by escaping into the cytoplasm. Avoidance of the host immune defenses is key to the success of a pathogen. Several common themes again are employed, including antigenic variation, camouflage by binding host molecules, and enzymatic degradation of host immune components. Most virulence factors are found on the bacterial surface or secreted into their immediate environment, yet virulence factors operate through a relatively small number of microbial secretion systems. The expression of bacterial pathogenicity is dependent upon complex regulatory circuits. However, pathogens use only a small number of biochemical families to express distinct functional factors at the appropriate time that causes infection. Finally, virulence factors maintained on mobile genetic elements and pathogenicity islands ensure that new strains of pathogens evolve constantly. Comprehension of these common themes in microbial pathogenicity is critical to the understanding and study of bacterial virulence mechanisms and to the development of new "anti-virulence" agents, which are so desperately needed to replace antibiotics. PMID:9184008

Ebola Virus Glycoprotein Promotes Enhanced Viral Egress by Preventing Ebola VP40 From Associating With the Host Restriction Factor BST2/Tetherin.

PubMed

Gustin, Jean K; Bai, Ying; Moses, Ashlee V; Douglas, Janet L

2015-10-01

BST2/tetherin is an innate immune molecule with the unique ability to restrict the egress of human immunodeficiency virus (HIV) and other enveloped viruses, including Ebola virus (EBOV). Coincident with this discovery was the finding that the HIV Vpu protein down-regulates BST2 from the cell surface, thereby promoting viral release. Evidence suggests that the EBOV envelope glycoprotein (GP) also counteracts BST2, although the mechanism is unclear. We find that total levels of BST2 remain unchanged in the presence of GP, whereas surface BST2 is significantly reduced. GP is known to sterically mask surface receptors via its mucin domain. Our evaluation of mutant GP molecules indicate that masking of BST2 by GP is probably responsible for the apparent surface BST2 down-regulation; however, this masking does not explain the observed virus-like particle egress enhancement. We discovered that VP40 coimmunoprecipitates and colocalizes with BST2 in the absence but not in the presence of GP. These results suggest that GP may overcome the BST2 restriction by blocking an interaction between VP40 and BST2. Furthermore, we have observed that GP may enhance BST2 incorporation into virus-like particles. Understanding this novel EBOV immune evasion strategy will provide valuable insights into the pathogenicity of this deadly pathogen. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

AMP-activated Protein Kinase As a Target For Pathogens: Friends Or Foes?

PubMed

Moreira, Diana; Silvestre, Ricardo; Cordeiro-da-Silva, Anabela; Estaquier, Jérôme; Foretz, Marc; Viollet, Benoit

2016-01-01

Intracellular pathogens are known to manipulate host cell regulatory pathways to establish an optimal environment for their growth and survival. Pathogens employ active mechanisms to hijack host cell metabolism and acquire existing nutrient and energy store. The role of the cellular energy sensor AMP-activated protein kinase (AMPK) in the regulation of cellular energy homeostasis is well documented. Here, we highlight recent advances showing the importance of AMPK signaling in pathogen-host interactions. Pathogens interact with AMPK by a variety of mechanisms aimed at reprogramming host cell metabolism to their own benefit. Stimulation of AMPK activity provides an efficient process to rapidly adapt pathogen metabolism to the major nutritional changes often encountered during the different phases of infection. However, inhibition of AMPK is also used by pathogens to manipulate innate host response, indicating that AMPK appears relevant to restriction of pathogen infection. We also document the effects of pharmacological AMPK modulators on pathogen proliferation and survival. This review illustrates intricate pathogen-AMPK interactions that may be exploited to the development of novel anti-pathogen therapies.

AMP-activated protein kinase as a target for pathogens: friends or foes?

PubMed Central

Moreira, Diana; Silvestre, Ricardo; Cordeiro-Da-Silva, Anabela; Estaquier, Jérôme; Foretz, Marc; Viollet, Benoit

2016-01-01

Intracellular pathogens are known to manipulate host cell regulatory pathways to establish an optimal environment for their growth and survival. Pathogens employ active mechanisms to hijack host cell metabolism and acquire existing nutrient and energy store. The role of the cellular energy sensor AMP-activated protein kinase (AMPK) in the regulation of cellular energy homeostasis is well documented. Here, we highlight recent advances showing the importance of AMPK signaling in pathogen-host interactions. Pathogens interact with AMPK by a variety of mechanisms aimed at reprogramming host cell metabolism to their own benefit. Stimulation of AMPK activity provides an efficient process to rapidly adapt pathogen metabolism to the major nutritional changes often encountered during the different phases of infection. However, inhibition of AMPK is also used by pathogens to manipulate innate host response, indicating that AMPK appears relevant to restriction of pathogen infection. We also document the effects of pharmacological AMPK modulators on pathogen proliferation and survival. This review illustrates intricate pathogen-AMPK interactions that maybe exploited to the development of novel anti-pathogen therapies. PMID:25882224

Immune response of T cells during herpes simplex virus type 1 (HSV-1) infection.

PubMed

Zhang, Jie; Liu, Huan; Wei, Bin

Herpes simplex virus type 1 (HSV-1), a neurotropic member of the alphaherpes virus family, is among the most prevalent and successful human pathogens. HSV-1 can cause serious diseases at every stage of life including fatal disseminated disease in newborns, cold sores, eye disease, and fatal encephalitis in adults. HSV-1 infection can trigger rapid immune responses, and efficient inhibition and clearance of HSV-1 infection rely on both the innate and adaptive immune responses of the host. Multiple strategies have been used to restrict host innate immune responses by HSV-1 to facilitate its infection in host cells. The adaptive immunity of the host plays an important role in inhibiting HSV-1 infections. The activation and regulation of T cells are the important aspects of the adaptive immunity. They play a crucial role in host-mediated immunity and are important for clearing HSV-1. In this review, we examine the findings on T cell immune responses during HSV-1 infection, which hold promise in the design of new vaccine candidates for HSV-1.

Immune response of T cells during herpes simplex virus type 1 (HSV-1) infection*

PubMed Central

Zhang, Jie; Liu, Huan; Wei, Bin

2017-01-01

Herpes simplex virus type 1 (HSV-1), a neurotropic member of the alphaherpes virus family, is among the most prevalent and successful human pathogens. HSV-1 can cause serious diseases at every stage of life including fatal disseminated disease in newborns, cold sores, eye disease, and fatal encephalitis in adults. HSV-1 infection can trigger rapid immune responses, and efficient inhibition and clearance of HSV-1 infection rely on both the innate and adaptive immune responses of the host. Multiple strategies have been used to restrict host innate immune responses by HSV-1 to facilitate its infection in host cells. The adaptive immunity of the host plays an important role in inhibiting HSV-1 infections. The activation and regulation of T cells are the important aspects of the adaptive immunity. They play a crucial role in host-mediated immunity and are important for clearing HSV-1. In this review, we examine the findings on T cell immune responses during HSV-1 infection, which hold promise in the design of new vaccine candidates for HSV-1. PMID:28378566

Controlled transition dipole alignment of energy donor and energy acceptor molecules in doped organic crystals, and the effect on intermolecular Förster energy transfer.

PubMed

Wang, Huan; Yue, Bailing; Xie, Zengqi; Gao, Bingrong; Xu, Yuanxiang; Liu, Linlin; Sun, Hongbo; Ma, Yuguang

2013-03-14

The orientation factor κ(2) ranging from 0 to 4, which depends on the relative orientation of the transition dipoles of the energy donor (D) and the energy acceptor (A) in space, is one of the pivotal factors deciding the efficiency and directionality of resonance energy transfer (RET) in a D-A molecular system. In this work, tetracene (Tc) and pentacene (Pc) are successfully doped in a trans-1,4-distyrylbenzene (DSB) crystalline lattice to form definite D-A mutually perpendicular transition dipole orientations. The cross D-A dipole arrangement results in an extremely small orientation factor, which is about two orders smaller than that in the disordered films. The energy transfer properties from the host (DSB) to the guest (Tc/Pc) were investigated in detail by steady-state as well as time-resolved fluorescence spectroscopy. Our experimental research results show that the small value of κ(2) allows less or partial energy transfer from the host (DSB) to the guest (Tc) in a wide range of guest concentration, with the Förster distance of around 1.5 nm. By controlling the doping concentrations in the Tc and Pc doubly doped DSB crystals, we demonstrate, as an example, for the first time the application of the restricted energy transfer by D-A cross transition dipole arrangement for preparation of a large-size, white-emissive organic crystal with the CIE coordinates of (0.36, 0.37) approaching an ideal white light. In contrast, Tc is also doped in an anthracene crystalline lattice to form head-to-tail D-A transition dipole alignment, which is proved to be highly effective to promote the intermolecular energy transfer. In this doped system, the orientation factor is relatively large and the Förster distance is around 7 nm.

Trojan Horse Transit Contributes to Blood-Brain Barrier Crossing of a Eukaryotic Pathogen

PubMed Central

Santiago-Tirado, Felipe H.; Onken, Michael D.; Cooper, John A.; Klein, Robyn S.

2017-01-01

ABSTRACT The blood-brain barrier (BBB) protects the central nervous system (CNS) by restricting the passage of molecules and microorganisms. Despite this barrier, however, the fungal pathogen Cryptococcus neoformans invades the brain, causing a meningoencephalitis that is estimated to kill over 600,000 people annually. Cryptococcal infection begins in the lung, and experimental evidence suggests that host phagocytes play a role in subsequent dissemination, although this role remains ill defined. Additionally, the disparate experimental approaches that have been used to probe various potential routes of BBB transit make it impossible to assess their relative contributions, confounding any integrated understanding of cryptococcal brain entry. Here we used an in vitro model BBB to show that a “Trojan horse” mechanism contributes significantly to fungal barrier crossing and that host factors regulate this process independently of free fungal transit. We also, for the first time, directly imaged C. neoformans-containing phagocytes crossing the BBB, showing that they do so via transendothelial pores. Finally, we found that Trojan horse crossing enables CNS entry of fungal mutants that cannot otherwise traverse the BBB, and we demonstrate additional intercellular interactions that may contribute to brain entry. Our work elucidates the mechanism of cryptococcal brain invasion and offers approaches to study other neuropathogens. PMID:28143979

Human Retroviruses: Methods and Protocols

PubMed Central

Zhao, Gongpu; Zhang, Peijun

2015-01-01

Summary After virus fusion with a target cell, the viral core is released into the host cell cytoplasm and undergoes a controlled disassembly process, termed uncoating, before or as reverse transcription takes place. The cellular protein TRIM5α is a host cell restriction factor that blocks HIV-1 infection in rhesus macaque cells by targeting the viral capsid and inducing premature uncoating. The molecular mechanism of the interaction between capsid and TRIM5α remains unclear. Here, we describe an approach that utilizes cryo-electron microscopy (cryoEM) to examine the structural changes exerted on HIV-1 capsid (CA) assembly by TRIM5α binding. The TRIM5α interaction sites on CA assembly were further dissected by combining cryoEM with pair-wise cysteine mutations that crosslink CA either within a CA hexamer or between CA hexamers. Based on the structural information from cryoEM and crosslinking results from in vitro CA assemblies and purified intact HIV-1 cores, we demonstrate that direct binding of TRIM5α CC-SPRY domains to the viral capsid results in disruption and fragmentation of the surface lattice of HIV-1 capsid, specifically at inter-hexamer interfaces. The method described here can be easily adopted to study other important interactions in multi-protein complexes. PMID:24158810

A Legume Genetic Framework Controls Infection of Nodules by Symbiotic and Endophytic Bacteria

PubMed Central

Zgadzaj, Rafal; James, Euan K.; Kelly, Simon; Kawaharada, Yasuyuki; de Jonge, Nadieh; Jensen, Dorthe B.; Madsen, Lene H.; Radutoiu, Simona

2015-01-01

Legumes have an intrinsic capacity to accommodate both symbiotic and endophytic bacteria within root nodules. For the symbionts, a complex genetic mechanism that allows mutual recognition and plant infection has emerged from genetic studies under axenic conditions. In contrast, little is known about the mechanisms controlling the endophytic infection. Here we investigate the contribution of both the host and the symbiotic microbe to endophyte infection and development of mixed colonised nodules in Lotus japonicus. We found that infection threads initiated by Mesorhizobium loti, the natural symbiont of Lotus, can selectively guide endophytic bacteria towards nodule primordia, where competent strains multiply and colonise the nodule together with the nitrogen-fixing symbiotic partner. Further co-inoculation studies with the competent coloniser, Rhizobium mesosinicum strain KAW12, show that endophytic nodule infection depends on functional and efficient M. loti-driven Nod factor signalling. KAW12 exopolysaccharide (EPS) enabled endophyte nodule infection whilst compatible M. loti EPS restricted it. Analysis of plant mutants that control different stages of the symbiotic infection showed that both symbiont and endophyte accommodation within nodules is under host genetic control. This demonstrates that when legume plants are exposed to complex communities they selectively regulate access and accommodation of bacteria occupying this specialized environmental niche, the root nodule. PMID:26042417

Latent Tuberculosis Infection: Myths, Models, and Molecular Mechanisms

PubMed Central

Dutta, Noton K.

2014-01-01

SUMMARY The aim of this review is to present the current state of knowledge on human latent tuberculosis infection (LTBI) based on clinical studies and observations, as well as experimental in vitro and animal models. Several key terms are defined, including “latency,” “persistence,” “dormancy,” and “antibiotic tolerance.” Dogmas prevalent in the field are critically examined based on available clinical and experimental data, including the long-held beliefs that infection is either latent or active, that LTBI represents a small population of nonreplicating, “dormant” bacilli, and that caseous granulomas are the haven for LTBI. The role of host factors, such as CD4+ and CD8+ T cells, T regulatory cells, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ), in controlling TB infection is discussed. We also highlight microbial regulatory and metabolic pathways implicated in bacillary growth restriction and antibiotic tolerance under various physiologically relevant conditions. Finally, we pose several clinically important questions, which remain unanswered and will serve to stimulate future research on LTBI. PMID:25184558

Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck

PubMed Central

Zaraket, Hassan; Baranovich, Tatiana; Kaplan, Bryan S.; Carter, Robert; Song, Min-Suk; Paulson, James C.; Rehg, Jerold E.; Bahl, Justin; Crumpton, Jeri C.; Seiler, Jon; Edmonson, Michael; Wu, Gang; Karlsson, Erik; Fabrizio, Thomas; Zhu, Huachen; Guan, Yi; Husain, Matloob; Schultz-Cherry, Stacey; Krauss, Scott; McBride, Ryan; Webster, Robert G.; Govorkova, Elena A.; Zhang, Jinghui; Russell, Charles J.; Webby, Richard J.

2015-01-01

Human infection with avian influenza A(H7N9) virus is associated mainly with the exposure to infected poultry. The factors that allow interspecies transmission but limit human-to-human transmission are unknown. Here we show that A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. In contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form. Airborne transmission in ferrets is accompanied by the mutations in PB1, NP and NA genes that reduce viral polymerase and neuraminidase activity. Therefore, while A(H7N9) virus can infect mammals, further adaptation appears to incur a fitness cost. Our results reveal that a tight genetic bottleneck during avian-to-mammalian transmission is a limiting factor in A(H7N9) influenza virus adaptation to mammals. This previously unrecognized biological mechanism limiting species jumps provides a measure of adaptive potential and may serve as a risk assessment tool for pandemic preparedness. PMID:25850788

Establishment of an intermittent cold stress model using Tupaia belangeri and evaluation of compound C737 targeting neuron-restrictive silencer factor

PubMed Central

Hai-Ying, Chi; Nagano, Kiori; Ezzikouri, Sayeh; Yamaguchi, Chiho; Kayesh, Mohammad Enamul Hoque; Rebbani, Khadija; Kitab, Bouchra; Nakano, Hirohumi; Kouji, Hiroyuki; Kohara, Michinori; Tsukiyama-Kohara, Kyoko

2016-01-01

Previous studies have shown that intermittent cold stress (ICS) induces depression-like behaviors in mammals. Tupaia belangeri (the tree shrew) is the only experimental animal other than the chimpanzee that has been shown to be susceptible to infection by hepatitis B and C viruses. Moreover, full genome sequence analysis has revealed strong homology between host proteins in Tupaia and in humans and other primates. Tupaia neuromodulator receptor proteins are also known to have a high degree of homology with their corresponding primate proteins. Based on these similarities, we hypothesized that induction of ICS in Tupaia would provide a useful animal model of stress responses. We exposed young adult Tupaia to ICS and observed decreases in body temperature and body weight in both female and male Tupaia, suggesting that Tupaia are an appropriate animal model for ICS studies. We further examined the efficacy of a new small-molecule compound, C737, against the effects of ICS. C737 mimics the helical structure of neuron-restrictive silencer factor (NRSF/REST), which regulates a wide range of target genes involved in neuronal function and pain modulation. Treatment with C737 significantly reduced stress-induced weight loss in female Tupaia; these effects were stronger than those elicited by the antidepressant agomelatine. These results suggest that Tupaia represents a useful non-rodent ICS model. Our data also provide new insights into the function of NRSF/REST in stress-induced depression and other disorders with epigenetic influences or those with high prevalence in women. PMID:27041457

Geographically structured host specificity is caused by the range expansions and host shifts of a symbiotic fungus.

PubMed

Wolfe, Benjamin E; Pringle, Anne

2012-04-01

The inability to associate with local species may constrain the spread of mutualists arriving to new habitats, but the fates of introduced, microbial mutualists are largely unknown. The deadly poisonous ectomycorrhizal fungus Amanita phalloides (the death cap) is native to Europe and introduced to the East and West Coasts of North America. By cataloging host associations across the two continents, we record dramatic changes in specificity among the three ranges. On the East Coast, where the fungus is restricted in its distribution, it associates almost exclusively with pines, which are rarely hosts of A. phalloides in its native range. In California, where the fungus is widespread and locally abundant, it associates almost exclusively with oaks, mirroring the host associations observed in Europe. The most common host of the death cap in California is the endemic coast live oak (Quercus agrifolia), and the current distribution of A. phalloides appears constrained within the distribution of Q. agrifolia. In California, host shifts to native plants are also associated with a near doubling in the resources allocated to sexual reproduction and a prolonged fruiting period; mushrooms are twice as large as they are elsewhere and mushrooms are found throughout the year. Host and niche shifts are likely to shape the continuing range expansion of A. phalloides and other ectomycorrhizal fungi introduced across the world.

The hidden life of integrative and conjugative elements

PubMed Central

Delavat, François; Miyazaki, Ryo; Carraro, Nicolas; Pradervand, Nicolas

2017-01-01

Abstract Integrative and conjugative elements (ICEs) are widespread mobile DNA that transmit both vertically, in a host-integrated state, and horizontally, through excision and transfer to new recipients. Different families of ICEs have been discovered with more or less restricted host ranges, which operate by similar mechanisms but differ in regulatory networks, evolutionary origin and the types of variable genes they contribute to the host. Based on reviewing recent experimental data, we propose a general model of ICE life style that explains the transition between vertical and horizontal transmission as a result of a bistable decision in the ICE–host partnership. In the large majority of cells, the ICE remains silent and integrated, but hidden at low to very low frequencies in the population specialized host cells appear in which the ICE starts its process of horizontal transmission. This bistable process leads to host cell differentiation, ICE excision and transfer, when suitable recipients are present. The ratio of ICE bistability (i.e. ratio of horizontal to vertical transmission) is the outcome of a balance between fitness costs imposed by the ICE horizontal transmission process on the host cell, and selection for ICE distribution (i.e. ICE ‘fitness’). From this emerges a picture of ICEs as elements that have adapted to a mostly confined life style within their host, but with a very effective and dynamic transfer from a subpopulation of dedicated cells. PMID:28369623

Geographically structured host specificity is caused by the range expansions and host shifts of a symbiotic fungus

PubMed Central

Wolfe, Benjamin E; Pringle, Anne

2012-01-01

The inability to associate with local species may constrain the spread of mutualists arriving to new habitats, but the fates of introduced, microbial mutualists are largely unknown. The deadly poisonous ectomycorrhizal fungus Amanita phalloides (the death cap) is native to Europe and introduced to the East and West Coasts of North America. By cataloging host associations across the two continents, we record dramatic changes in specificity among the three ranges. On the East Coast, where the fungus is restricted in its distribution, it associates almost exclusively with pines, which are rarely hosts of A. phalloides in its native range. In California, where the fungus is widespread and locally abundant, it associates almost exclusively with oaks, mirroring the host associations observed in Europe. The most common host of the death cap in California is the endemic coast live oak (Quercus agrifolia), and the current distribution of A. phalloides appears constrained within the distribution of Q. agrifolia. In California, host shifts to native plants are also associated with a near doubling in the resources allocated to sexual reproduction and a prolonged fruiting period; mushrooms are twice as large as they are elsewhere and mushrooms are found throughout the year. Host and niche shifts are likely to shape the continuing range expansion of A. phalloides and other ectomycorrhizal fungi introduced across the world. PMID:22134645

Epistatic interactions between Fc (GM) and FcγR genes and the host control of human immunodeficiency virus replication.

PubMed

Deepe, Raymond N; Kistner-Griffin, Emily; Martin, Jeffrey N; Deeks, Steven G; Pandey, Janardan P

2012-03-01

Host genetic factors are thought to contribute to the interindividual differences in the control of human immunodeficiency virus (HIV) replication. The aim of the present investigation was to determine whether genes encoding GM and KM allotypes-genetic markers of immunoglobulin γ and κ chains, respectively-and those encoding Fcγ receptor (FcγR) IIa and IIIa are associated with the host control of HIV replication. A case-control design was employed among HIV-infected subjects, with a group that spontaneously controlled HIV replication ("controllers") as cases (n = 73) and those who did not control replication as controls (n = 100). Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism, direct DNA sequencing, and TaqMan genotyping assays. In Caucasian Americans, certain combinations of FcγR and GM genotypes were differentially distributed between controllers and noncontrollers. Among the noncarriers of the FcγRIIa arginine allele, GM21 noncarriers had over 7-fold greater odds of being controllers than the carriers of this allele (odds ratio [OR] = 7.47). These GM determinants also interacted with FcγRIIIa alleles. Among the carriers of the FcγRIIIa valine allele, GM21 noncarriers had over 3-fold greater odds of being controllers than the carriers of this allele (OR = 3.26). These results demonstrate epistatic interactions of genes on chromosomes 14 (GM) and 1 (FcγR) in influencing the control of HIV replication. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Transcriptome Analysis of Green Peach Aphid (Myzus persicae): Insight into Developmental Regulation and Inter-Species Divergence

PubMed Central

Ji, Rui; Wang, Yujun; Cheng, Yanbin; Zhang, Meiping; Zhang, Hong-Bin; Zhu, Li; Fang, Jichao; Zhu-Salzman, Keyan

2016-01-01

Green peach aphid (Myzus persicae) and pea aphid (Acyrthosiphon pisum) are two phylogenetically closely related agricultural pests. While pea aphid is restricted to Fabaceae, green peach aphid feeds on hundreds of plant species from more than 40 families. Transcriptome comparison could shed light on the genetic factors underlying the difference in host range between the two species. Furthermore, a large scale study contrasting gene expression between immature nymphs and fully developed adult aphids would fill a previous knowledge gap. Here, we obtained transcriptomic sequences of green peach aphid nymphs and adults, respectively, using Illumina sequencing technology. A total of 2244 genes were found to be differentially expressed between the two developmental stages, many of which were associated with detoxification, hormone production, cuticle formation, metabolism, food digestion, and absorption. When searched against publically available pea aphid mRNA sequences, 13,752 unigenes were found to have no homologous counterparts. Interestingly, many of these unigenes that could be annotated in other databases were involved in the “xenobiotics biodegradation and metabolism” pathway, suggesting the two aphids differ in their adaptation to secondary metabolites of host plants. Conversely, 3989 orthologous gene pairs between the two species were subjected to calculations of synonymous and nonsynonymous substitutions, and 148 of the genes potentially evolved in response to positive selection. Some of these genes were predicted to be associated with insect-plant interactions. Our study has revealed certain molecular events related to aphid development, and provided some insight into biological variations in two aphid species, possibly as a result of host plant adaptation. PMID:27812361

The development of pathogen resistance in Daphnia magna: implications for disease spread in age-structured populations.

PubMed

Garbutt, Jennie S; O'Donoghue, Anna J P; McTaggart, Seanna J; Wilson, Philip J; Little, Tom J

2014-11-01

Immunity in vertebrates is well established to develop with time, but the ontogeny of defence in invertebrates is markedly less studied. Yet, age-specific capacity for defence against pathogens, coupled with age structure in populations, has widespread implications for disease spread. Thus, we sought to determine the susceptibility of hosts of different ages in an experimental invertebrate host-pathogen system. In a series of experiments, we show that the ability of Daphnia magna to resist its natural bacterial pathogen Pasteuria ramosa changes with host age. Clonal differences make it difficult to draw general conclusions, but the majority of observations indicate that resistance increases early in the life of D. magna, consistent with the idea that the defence system develops with time. Immediately following this, at about the time when a daphnid would be most heavily investing in reproduction, resistance tends to decline. Because many ecological factors influence the age structure of Daphnia populations, our results highlight a broad mechanism by which ecological context can affect disease epidemiology. We also show that a previously observed protective effect of restricted maternal food persists throughout the entire juvenile period, and that the protective effect of prior treatment with a small dose of the pathogen ('priming') persists for 7 days, observations that reinforce the idea that immunity in D. magna can change over time. Together, our experiments lead us to conclude that invertebrate defence capabilities have an ontogeny that merits consideration with respect to both their immune systems and the epidemic spread of infection. © 2014. Published by The Company of Biologists Ltd.

The dermatophytes.

PubMed Central

Weitzman, I; Summerbell, R C

1995-01-01

The etiologic agents of the dermatophytoses (ringworm) are classified in three anamorphic (asexual or imperfect) genera, Epidermophyton, Microsporum, and Trichophyton. Species capable of reproducing sexually belong in the teleomorphic genus, Arthroderma, of the Ascomycota. On the basis of primary habitat association, they may be grouped as geophilic (soil associated), zoophilic, and anthropophilic. Adaptation to growth on humans by most geophilic species resulted in diminished loss of sporulation, sexuality, and other soil-associated characteristics. The dermatophytes have the ability to invade keratinized tissue (skin, hair, and nails) but are usually restricted to the nonliving cornified layer of the epidermis because of their inability to penetrate viable tissue of an immunocompetent host. However, invasion does elicit a host response ranging from mild to severe. Acid proteinases, elastase, keratinases, and other proteinases reportedly act as virulence factors. The development of cell-mediated immunity correlated with delayed hypersensitivity and an inflammatory response is associated with clinical cure, whereas the lack of or a defective cell-mediated immunity predisposes the host to chronic or recurrent dermatophyte infection. Chronic dermatophytosis is mostly caused by Trichophyton rubrum, and there is some evidence that mannan produced by this fungus suppresses or diminishes the inflammatory response. Since dermatophytes cause a communicable disease, modes of transmission and control are discussed as well as a survey of recent trends in therapy. Collection of specimens, culture media, and tests for identification are also presented. Genetic studies have led to an understanding of incompatibility mechanisms, pleomorphism and variation, resistance to griseofulvin, and virulence. Molecular biology has contributed to our knowledge of the taxonomy and phylogenetic relationships of dermatophytes. PMID:7621400

Lipid A’s Structure Mediates Neisseria gonorrhoeae Fitness during Experimental Infection of Mice and Men

PubMed Central

Hobbs, Marcia M.; Anderson, James E.; Balthazar, Jacqueline T.; Kandler, Justin L.; Carlson, Russell W.; Ganguly, Jhuma; Begum, Afrin A.; Duncan, Joseph A.; Lin, Jessica T.; Sparling, P. Frederick; Jerse, Ann E.; Shafer, William M.

2013-01-01

ABSTRACT Phosphoethanolamine (PEA) on Neisseria gonorrhoeae lipid A influences gonococcal inflammatory signaling and susceptibility to innate host defenses in in vitro models. Here, we evaluated the role of PEA-decorated gonococcal lipid A in competitive infections in female mice and in male volunteers. We inoculated mice and men with mixtures of wild-type N. gonorrhoeae and an isogenic mutant that lacks the PEA transferase, LptA. LptA production conferred a marked survival advantage for wild-type gonococci in the murine female genital tract and in the human male urethra. Our studies translate results from test tube to animal model and into the human host and demonstrate the utility of the mouse model for studies of virulence factors of the human-specific pathogen N. gonorrhoeae that interact with non-host-restricted elements of innate immunity. These results validate the use of gonococcal LptA as a potential target for development of novel immunoprophylactic strategies or antimicrobial treatments. IMPORTANCE Gonorrhea is one of the most common bacterial sexually transmitted infections, and increasing antibiotic resistance threatens the use of currently available antimicrobial therapies. In this work, encompassing in vitro studies and in vivo studies of animal and human models of experimental genital tract infection, we document the importance of lipid A’s structure, mediated by a single bacterial enzyme, LptA, in enhancing the fitness of Neisseria gonorrhoeae. The results of these studies suggest that novel agents targeting LptA may offer urgently needed prevention or treatment strategies for gonorrhea. PMID:24255126

The biological and practical significance of antigenic variability in protective T cell responses against Theileria parva.

PubMed

Morrison, W I

2007-08-19

The evolution of antigenically distinct pathogen strains that fail to cross-protect is well documented for pathogens controlled primarily by humoral immune responses. Unlike antibodies, which recognise native proteins, protective T cells can potentially recognise epitopes in a variety of proteins that are not necessarily displayed on the pathogen surface. Moreover, individual hosts of different MHC genotypes generally respond to different sets of epitopes. It is therefore less easy to envisage how strain restricted immunity can arise for pathogens controlled by T cell responses, particularly in antigenically complex parasites. Nevertheless, strain restricted immunity is clearly a feature of a number of parasitic infections, where immunity is known to be mediated by T cell responses. One such parasite is Theileria parva which induces potent CD8 T cell responses that play an important role in immunity. CD8 T cells specific for parasitized lymphoblasts exhibit strain specificity, which appears to correlate with the ability of parasite strains to cross-protect. Studies using recently identified T. parva antigens recognised by CD8 T cells have shown that the strain restricted nature of immunity is a consequence of the CD8 T cell response in individual animals being focused on a limited number of dominant polymorphic antigenic determinants. Responses in animals of different MHC genotypes are often directed to different parasite antigens, indicating that, at the host population level, a larger number of parasite proteins can serve as targets for the protective T cell response. Nevertheless, the finding that parasite strains show overlapping antigenic profiles, probably as a consequence of sexual recombination, suggests that induction of responses to an extended but limited set of antigens in individual animals may overcome the strain restricted nature of immunity.

CRISPR–Cas9 Genetic Analysis of Virus–Host Interactions

PubMed Central

Gebre, Makda; Nomburg, Jason L.; Gewurz, Benjamin E.

2018-01-01

Clustered regularly interspaced short palindromic repeats (CRISPR) has greatly expanded the ability to genetically probe virus–host interactions. CRISPR systems enable focused or systematic, genomewide studies of nearly all aspects of a virus lifecycle. Combined with its relative ease of use and high reproducibility, CRISPR is becoming an essential tool in studies of the host factors important for viral pathogenesis. Here, we review the use of CRISPR–Cas9 for the loss-of-function analysis of host dependency factors. We focus on the use of CRISPR-pooled screens for the systematic identification of host dependency factors, particularly in Epstein–Barr virus-transformed B cells. We also discuss the use of CRISPR interference (CRISPRi) and gain-of-function CRISPR activation (CRISPRa) approaches to probe virus–host interactions. Finally, we comment on the future directions enabled by combinatorial CRISPR screens. PMID:29385696

CRISPR-Cas9 Genetic Analysis of Virus-Host Interactions.

PubMed

Gebre, Makda; Nomburg, Jason L; Gewurz, Benjamin E

2018-01-30

Clustered regularly interspaced short palindromic repeats (CRISPR) has greatly expanded the ability to genetically probe virus-host interactions. CRISPR systems enable focused or systematic, genomewide studies of nearly all aspects of a virus lifecycle. Combined with its relative ease of use and high reproducibility, CRISPR is becoming an essential tool in studies of the host factors important for viral pathogenesis. Here, we review the use of CRISPR-Cas9 for the loss-of-function analysis of host dependency factors. We focus on the use of CRISPR-pooled screens for the systematic identification of host dependency factors, particularly in Epstein-Barr virus-transformed B cells. We also discuss the use of CRISPR interference (CRISPRi) and gain-of-function CRISPR activation (CRISPRa) approaches to probe virus-host interactions. Finally, we comment on the future directions enabled by combinatorial CRISPR screens.

Aspergillosis and stem cell transplantation: An overview of experimental pathogenesis studies.

PubMed

Al-Bader, Nadia; Sheppard, Donald C

2016-11-16

Invasive aspergillosis is a life-threatening infection caused by the opportunistic filamentous fungus Aspergillus fumigatus. Patients undergoing haematopoietic stem cell transplant (HSCT) for the treatment of hematological malignancy are at particularly high risk of developing this fatal infection. The susceptibility of HSCT patients to infection with A. fumigatus is a consequence of a complex interplay of both fungal and host factors. Here we review our understanding of the host-pathogen interactions underlying the susceptibility of the immunocompromised host to infection with A. fumigatus with a focus on the experimental validation of fungal and host factors relevant to HSCT patients. These include fungal factors such as secondary metabolites, cell wall constituents, and metabolic adaptations that facilitate immune evasion and survival within the host microenvironment, as well as the innate and adaptive immune responses involved in host defense against A. fumigatus.

Nuclear Ribosomal DNA Variation and Pathogenic Specialization in Alternaria Fungi Known To Produce Host-Specific Toxins †

PubMed Central

Kusaba, Motoaki; Tsuge, Takashi

1994-01-01

A total of 99 strains of 11 Alternaria species, including 68 strains of seven fungi known to produce host-specific toxins, were subjected to analysis of restriction fragment length polymorphism (RFLP) in nuclear ribosomal DNA (rDNA). Total DNA was digested with XbaI, and the Southern blots were probed with a nuclear rDNA clone of Alternaria kikuchiana. The hybridization gave 17 different RFLPs from the 99 strains. On the basis of these RFLPs, populations of host-specific toxin-producing fungi could not be differentiated from one another nor from nonpathogenic A. alternata. Each population of the toxin-producing fungi carried rDNA variants. Nine different types, named A1 to A6 and B1 to B3, were detected among the toxin-producing fungi and nonpathogenic A. alternata. All of the populations contained the type A4 variant, and the other rDNA types were also shared by different toxin-producing fungi and A. alternata. In contrast, Alternaria species that are morphologically distinguishable from A. alternata could be differentiated from A. alternata on the basis of the rDNA RFLPs. Polymorphisms in rDNA digested with HaeIII and MspI were also evaluated in 61 Alternaria strains. These restriction enzymes produced 31 variations among all of the samples. The seven toxin-producing fungi and nonpathogenic A. alternata could not be resolved by phylogenetic analysis based on the RFLPs, although they could be differentiated from the other Alternaria species studied. These results provide support for the hypothesis that Alternaria fungi known to produce host-specific toxins are intraspecific variants of A. alternata specialized in pathogenicity. Images PMID:16349367

A limited innate immune response is induced by a replication-defective herpes simplex virus vector following delivery to the murine central nervous system

PubMed Central

Zeier, Zane; Aguilar, J Santiago; Lopez, Cecilia M; Devi-Rao, G B; Watson, Zachary L; Baker, Henry V; Wagner, Edward K; Bloom, David C

2010-01-01

Herpes simplex virus type 1 (HSV-1)–based vectors readily transduce neurons and have a large payload capacity, making them particularly amenable to gene therapy applications within the central nervous system (CNS). Because aspects of the host responses to HSV-1 vectors in the CNS are largely unknown, we compared the host response of a nonreplicating HSV-1 vector to that of a replication-competent HSV-1 virus using microarray analysis. In parallel, HSV-1 gene expression was tracked using HSV-specific oligonucleotide-based arrays in order to correlate viral gene expression with observed changes in host response. Microarray analysis was performed following stereotactic injection into the right hippocampal formation of mice with either a replication-competent HSV-1 or a nonreplicating recombinant of HSV-1, lacking the ICP4 gene (ICP4−). Genes that demonstrated a significant change (P < .001) in expression in response to the replicating HSV-1 outnumbered those that changed in response to mock or nonreplicating vector by approximately 3-fold. Pathway analysis revealed that both the replicating and nonreplicating vectors induced robust antigen presentation but only mild interferon, chemokine, and cytokine signaling responses. The ICP4− vector was restricted in several of the Toll-like receptor-signaling pathways, indicating reduced stimulation of the innate immune response. These array analyses suggest that although the nonreplicating vector induces detectable activation of immune response pathways, the number and magnitude of the induced response is dramatically restricted compared to the replicating vector, and with the exception of antigen presentation, host gene expression induced by the non-replicating vector largely resembles mock infection. PMID:20095947

Soybean mosaic virus: A successful potyvirus with a wide distribution but restricted natural host range

USDA-ARS?s Scientific Manuscript database

Soybean mosaic virus (SMV) is a species within the genus Potyvirus, family Potyviridae. The family includes eight genera and almost a quarter of all known plant RNA viruses affecting agriculturally important plants. The Potyvirus genus is the largest with 160 species. The SMV genome consists of a si...

Avian coccidiosis as a prototype intestinal disease: Recent advances in host protective immunity and novel disease control strategies

USDA-ARS?s Scientific Manuscript database

Poultry meat consumption has increased globally by 50% since 2000, accounting for greater than 100 million tons in 2012. Multiple challenges confront the rising demand for poultry food products, including governmental restrictions on the use of antibiotic growth promoters and novel feedstuffs, high-...

Recent advances in host protective immunity and novel disease control strategies against intestinal protozoan infections in commercial poultry

USDA-ARS?s Scientific Manuscript database

Poultry meat consumption has increased globally by 50% since 2000, accounting for greater than 100 million tons in 2012. Multiple challenges confront the rising demand for poultry food products, including governmental restrictions on the use of antibiotic growth promoters and novel feedstuffs, high-...

Single inclusion piezobarometry confirms high-temperature decompression path for Variscan granulites

NASA Astrophysics Data System (ADS)

Angel, Ross; Alvaro, Matteo; Mazzucchelli, Mattia; Nimis, Paolo; Nestola, Fabrizio

2016-04-01

The identification and chemistry of inclusions trapped in host minerals during growth of the host phase have long been used to infer P-T points on metamorphic paths. The determination of the remnant pressure on the inclusion, e.g., using data from X-ray diffractometry, birefringence analysis or Raman spectroscopy, provides an alternative method of barometry using elasticity theory. A remnant pressure in an inclusion is developed because the inclusion and the host have different thermal expansion and compressibilities, and the inclusion does not expand in response to P and T as would a free crystal. Instead it is restricted to expand only as much as the host mineral, and this constriction in volume can result in inclusions exhibiting over-pressures when the host is studied at room conditions. This concept has been known for a long time, but satisfactory quantitative modelling of inclusion-host systems based on non-linear elasticity theory and precise thermal-pressure euqations of state has only recently come available (Angel et al., 2014, 2015), even though it is still restricted to elastically isotropic minerals. No mineral is elastically isotropic, but garnets and diamond are almost so. Calculations show that diamonds trapped as inclusions in host silicates at P and T within the stability field of diamond should exhibit zero pressure when the samples are recovered to room conditions. However, some diamond inclusions in garnets in granulites are reported to exhibit significant residual overpressures (e.g., Kotková et al., 2011). This indicates that the inclusion was elastically re-equilibrated (e.g., by plastic flow in the garnet host) at high temperatures and lower pressures in the stability field of graphite, consistent also with the observed partial inversion of diamond to graphite. In this case, the elastic analysis of the diamond-in-garnet inclusions provides qualitative independent evidence that the Variscan granulites underwent pressure reduction at high temperatures. The extension of single inclusion piezobarometry to elastically anisotropic minerals will allow quantitative analysis of diamonds trapped in other minerals such as kyanite. This work was supported by ERC starting grant 307322 to Fabrizio Nestola and by the MIUR-SIR grant "MILE DEEp" (RBSI140351) to M. Alvaro. Angel R.J., Mazzucchelli M.L., Alvaro M., Nimis P. & Nestola F. (2014) Geobarometry from host-inclusion systems: the role of elastic relaxation. Am. Mineral., 99, 2146-2149. Angel R.J., Nimis P., Mazzucchelli M.L., Alvaro M. & Nestola F. (2015) How large are departures from lithostatic pressure? Constraints from host-inclusion elasticity. J. Metamorphic Geol., 33, 801-813. Kotková J, O'Brien P.J & Ziemann M.A. (2011)Diamond and coesite discovered in Saxony-type granulite: Solution to the Variscan garnet peridotite enigma. Geology, 39, 667-670.

Characterization of Erwinia chrysanthemi by pectinolytic isozyme polymorphism and restriction fragment length polymorphism analysis of PCR-amplified fragments of pel genes.

PubMed Central

Nassar, A; Darrasse, A; Lemattre, M; Kotoujansky, A; Dervin, C; Vedel, R; Bertheau, Y

1996-01-01

Conserved regions about 420 bp long of the pelADE cluster specific to Erwinia chrysanthemi were amplified by PCR and used to differentiate 78 strains of E. chrysanthemi that were obtained from different hosts and geographical areas. No PCR products were obtained from DNA samples extracted from other pectinolytic and nonpectinolytic species and genera. The pel fragments amplified from the E. chrysanthemi strains studied were compared by performing a restriction fragment length polymorphism (RFLP) analysis. On the basis of similarity coefficients derived from the RFLP analysis, the strains were separated into 16 PCR RFLP patterns grouped in six clusters, These clusters appeared to be correlated with other infraspecific levels of E. chrysanthemi classification, such as pathovar and biovar, and occasionally with geographical origin. Moreover, the clusters correlated well with the polymorphism of pectate lyase and pectin methylesterase isoenzymes. While the pectin methylesterase profiles correlated with host monocot-dicot classification, the pectate lyase polymorphism might reflect the cell wall microdomains of the plants belonging to these classes. PMID:8779560

Implications of climate change (global warming) for the healthcare system.

PubMed

Raffa, R B; Eltoukhy, N S; Raffa, K F

2012-10-01

Temperature-sensitive pathogenic species and their vectors and hosts are emerging in previously colder regions as a consequence of several factors, including global warming. As a result, an increasing number of people will be exposed to pathogens against which they have not previously needed defences. We illustrate this with a specific example of recent emergence of Cryptococcus gattii infections in more temperate climates. The outbreaks in more temperate climates of the highly virulent--but usually tropically restricted--C. gattii is illustrative of an anticipated growing challenge for the healthcare system. There is a need for preparedness by healthcare professionals in anticipation and for management of such outbreaks, including other infections whose recent increased prevalence in temperate climates can be at least partly associated with global warming. (Re)emergence of temperature-sensitive pathogenic species in more temperate climates will present new challenges for healthcare systems. Preparation for outbreaks should precede their occurrence. © 2012 Blackwell Publishing Ltd.

Transmembrane mucins as novel therapeutic targets.

PubMed

Constantinou, Pamela E; Danysh, Brian P; Dharmaraj, Neeraja; Carson, Daniel D

2011-11-01

Membrane-tethered mucin glycoproteins are abundantly expressed at the apical surfaces of simple epithelia, where they play important roles in lubricating and protecting tissues from pathogens and enzymatic attack. Notable examples of these mucins are MUC1, MUC4 and MUC16 (also known as cancer antigen 125). In adenocarcinomas, apical mucin restriction is lost and overall expression is often highly increased. High-level mucin expression protects tumors from killing by the host immune system, as well as by chemotherapeutic agents, and affords protection from apoptosis. Mucin expression can increase as the result of gene duplication and/or in response to hormones, cytokines and growth factors prevalent in the tumor milieu. Rises in the normally low levels of mucin fragments in serum have been used as markers of disease, such as tumor burden, for many years. Currently, several approaches are being examined that target mucins for immunization or nanomedicine using mucin-specific antibodies.

Indigenous and Invasive Fruit Fly Diversity along an Altitudinal Transect in Eastern Central Tanzania

PubMed Central

Geurts, Katrien; Mwatawala, Maulid; De Meyer, Marc

2012-01-01

The relative abundance of indigenous and invasive frugivorous fruit flies (Diptera: Tephritidae) was evaluated spatially and temporally along an altitudinal transect between 581–1650 m in the Uluguru Mountains near Morogoro, Tanzania. The polyphagous invasive fruit fly Bactrocera invadens Drew, Tsuruta, and White and the indigenous fruit fly Ceratitis rosa Karsch show a similar temporal pattern, but are largely separated spatially, with B. invadens being abundant at lower elevation and C. rosa predominant at higher elevation. The polyphagous indigenous C. cosyra (Walker) coincides with B. invadens but shows an inverse temporal pattern. The cucurbit feeders B. cucurbitae (Coquillett) and Dacus bivittatus (Bigot) show a similar temporal pattern, but the former is restricted to lower elevations. Host availability and climatic differences seem to be the determining factors to explain the differences in occurrence and abundance in time and space. PMID:22935017

Neutropenia during HIV Infection: Adverse Consequences and Remedies

PubMed Central

Shi, Xin; Sims, Matthew D; Hanna, Michel M; Xie, Ming; Gulick, Peter G; Zheng, Yong-Hui; Basson, Marc D; Zhang, Ping

2016-01-01

Neutropenia frequently occurs in patients with Human immunodeficiency virus (HIV) infection. Causes for neutropenia during HIV infection are multifactoral, including the viral toxicity to hematopoietic tissue, the use of myelotoxic agents for treatment, complication with secondary infections and malignancies, as well as the patient’s association with confounding factors which impair myelopoiesis. An increased prevalence and severity of neutropenia is commonly seen in advanced stages of HIV disease. Decline of neutrophil phagocytic defense in combination with the failure of adaptive immunity renders the host highly susceptible to developing fatal secondary infections. Neutropenia and myelosuppression also restrict the use of many antimicrobial agents for treatment of infections caused by HIV and opportunistic pathogens. In recent years, HIV infection has increasingly become a chronic disease because of progress in antiretroviral therapy (ART). Prevention and treatment of severe neutropenia becomes critical for improving the survival of HIV-infected patients. PMID:24654626

New Hepatitis B Virus of Cranes That Has an Unexpected Broad Host Range

PubMed Central

Prassolov, Alexej; Hohenberg, Heinz; Kalinina, Tatyana; Schneider, Carola; Cova, Lucyna; Krone, Oliver; Frölich, Kai; Will, Hans; Sirma, Hüseyin

2003-01-01

All hepadnaviruses known so far have a very limited host range, restricted to their natural hosts and a few closely related species. This is thought to be due mainly to sequence divergence in the large envelope protein and species-specific differences in host components essential for virus propagation. Here we report an infection of cranes with a novel hepadnavirus, designated CHBV, that has an unexpectedly broad host range and is only distantly evolutionarily related to avihepadnaviruses of related hosts. Direct DNA sequencing of amplified CHBV DNA as well a sequencing of cloned viral genomes revealed that CHBV is most closely related to, although distinct from, Ross' goose hepatitis B virus (RGHBV) and slightly less closely related to duck hepatitis B virus (DHBV). Phylogenetically, cranes are very distant from geese and ducks and are most closely related to herons and storks. Naturally occurring hepadnaviruses in the last two species are highly divergent in sequence from RGHBV and DHBV and do not infect ducks or do so only marginally. In contrast, CHBV from crane sera and recombinant CHBV produced from LMH cells infected primary duck hepatocytes almost as efficiently as DHBV did. This is the first report of a rather broad host range of an avihepadnavirus. Our data imply either usage of similar or identical entry pathways and receptors by DHBV and CHBV, unusual host and virus adaptation mechanisms, or divergent evolution of the host genomes and cellular components required for virus propagation. PMID:12525630

New hepatitis B virus of cranes that has an unexpected broad host range.

PubMed

Prassolov, Alexej; Hohenberg, Heinz; Kalinina, Tatyana; Schneider, Carola; Cova, Lucyna; Krone, Oliver; Frölich, Kai; Will, Hans; Sirma, Hüseyin

2003-02-01

All hepadnaviruses known so far have a very limited host range, restricted to their natural hosts and a few closely related species. This is thought to be due mainly to sequence divergence in the large envelope protein and species-specific differences in host components essential for virus propagation. Here we report an infection of cranes with a novel hepadnavirus, designated CHBV, that has an unexpectedly broad host range and is only distantly evolutionarily related to avihepadnaviruses of related hosts. Direct DNA sequencing of amplified CHBV DNA as well a sequencing of cloned viral genomes revealed that CHBV is most closely related to, although distinct from, Ross' goose hepatitis B virus (RGHBV) and slightly less closely related to duck hepatitis B virus (DHBV). Phylogenetically, cranes are very distant from geese and ducks and are most closely related to herons and storks. Naturally occurring hepadnaviruses in the last two species are highly divergent in sequence from RGHBV and DHBV and do not infect ducks or do so only marginally. In contrast, CHBV from crane sera and recombinant CHBV produced from LMH cells infected primary duck hepatocytes almost as efficiently as DHBV did. This is the first report of a rather broad host range of an avihepadnavirus. Our data imply either usage of similar or identical entry pathways and receptors by DHBV and CHBV, unusual host and virus adaptation mechanisms, or divergent evolution of the host genomes and cellular components required for virus propagation.

Depth and type of substrate influence the ability of Nasonia vitripennis to locate a host

PubMed Central

Frederickx, Christine; Dekeirsschieter, Jessica; Verheggen, François J.; Haubruge, Eric

2014-01-01

Abstract The foraging behaviour of a parasitoid insect species includes the host’s habitat and subsequent location of the host. Habitats substrate, substrate moisture, and light levels can affect the host searching of different species of parasitoids. However, the depth at which parasitoids concentrate their search effort is another important ecological characteristic and plays an important role in locating a host. Here, we investigated the ability of a pupal parasitoid, Nasonia vitripennis Walker (Hymenoptera: Pteromalidae), to penetrate and kill fly pupae located at different depths of the substrate. Three different types of substrate were tested: loam soil, compost, and vermiculite substrate. In both loam soil and compost, all of the parasitism activity was restricted to pupae placed directly on the surface. Parasitism activity in vermiculite showed that the average number of pupae parasitized decreased with depth of substrate. These results suggest that fly pupae situated deeper in the substrate are less subjected to parasitism by N. vitripennis . PMID:25373205

Evolutionary assembly of the milkweed fauna: cytochrome oxidase I and the age of Tetraopes beetles.

PubMed

Farrell, B D

2001-03-01

The insects that feed on the related plant families Apocynaceae and Asclepiadaceae (here collectively termed "milkweeds") comprise a "component community" of highly specialized, distinctive lineages of species that frequently sequester toxic cardiac glycosides from their host plants for defense against predators and are thus often aposematic, advertising their consequent unpalatability. Such sets of specialized lineages provide opportunities for comparative studies of the rate of adaptation, diversification, and habitat-related effects on molecular evolution. The cerambycid genus Tetraopes is the most diverse of the new world milkweed herbivores and the species are generally host specific, being restricted to single, different species of Asclepias, more often so than most other milkweed insects. Previous work revealed correspondence between the phylogeny of these beetles and that of their hosts. The present study provides analyses of near-complete DNA sequences for Tetraopes and relatives that are used to establish a molecular clock and temporal framework for Tetraopes evolution with their milkweed hosts. Copyright 2001 Academic Press.

Agrobacterium tumefaciens recognizes its host environment using ChvE to bind diverse plant sugars as virulence signals

PubMed Central

Hu, Xiaozhen; Zhao, Jinlei; DeGrado, William F.; Binns, Andrew N.

2013-01-01

Agrobacterium tumefaciens is a broad host range plant pathogen that combinatorially recognizes diverse host molecules including phenolics, low pH, and aldose monosaccharides to activate its pathogenic pathways. Chromosomal virulence gene E (chvE) encodes a periplasmic-binding protein that binds several neutral sugars and sugar acids, and subsequently interacts with the VirA/VirG regulatory system to stimulate virulence (vir) gene expression. Here, a combination of genetics, X-ray crystallography, and isothermal calorimetry reveals how ChvE binds the different monosaccharides and also shows that binding of sugar acids is pH dependent. Moreover, the potency of a sugar for vir gene expression is modulated by a transport system that also relies on ChvE. These two circuits tune the overall system to respond to sugar concentrations encountered in vivo. Finally, using chvE mutants with restricted sugar specificities, we show that there is host variation in regard to the types of sugars that are limiting for vir induction. PMID:23267119

Truncated CPSF6 Forms Higher-Order Complexes That Bind and Disrupt HIV-1 Capsid.

PubMed

Ning, Jiying; Zhong, Zhou; Fischer, Douglas K; Harris, Gemma; Watkins, Simon C; Ambrose, Zandrea; Zhang, Peijun

2018-07-01

Cleavage and polyadenylation specificity factor 6 (CPSF6) is a human protein that binds HIV-1 capsid and mediates nuclear transport and integration targeting of HIV-1 preintegration complexes. Truncation of the protein at its C-terminal nuclear-targeting arginine/serine-rich (RS) domain produces a protein, CPSF6-358, that potently inhibits HIV-1 infection by targeting the capsid and inhibiting nuclear entry. To understand the molecular mechanism behind this restriction, the interaction between CPSF6-358 and HIV-1 capsid was characterized using in vitro and in vivo assays. Purified CPSF6-358 protein formed oligomers and bound in vitro -assembled wild-type (WT) capsid protein (CA) tubes, but not CA tubes containing a mutation in the putative binding site of CPSF6. Intriguingly, binding of CPSF6-358 oligomers to WT CA tubes physically disrupted the tubular assemblies into small fragments. Furthermore, fixed- and live-cell imaging showed that stably expressed CPSF6-358 forms cytoplasmic puncta upon WT HIV-1 infection and leads to capsid permeabilization. These events did not occur when the HIV-1 capsid contained a mutation known to prevent CPSF6 binding, nor did they occur in the presence of a small-molecule inhibitor of capsid binding to CPSF6-358. Together, our in vitro biochemical and transmission electron microscopy data and in vivo intracellular imaging results provide the first direct evidence for an oligomeric nature of CPSF6-358 and suggest a plausible mechanism for restriction of HIV-1 infection by CPSF6-358. IMPORTANCE After entry into cells, the HIV-1 capsid, which contains the viral genome, interacts with numerous host cell factors to facilitate crucial events required for replication, including uncoating. One such host cell factor, called CPSF6, is predominantly located in the cell nucleus and interacts with HIV-1 capsid. The interaction between CA and CPSF6 is critical during HIV-1 replication in vivo Truncation of CPSF6 leads to its localization to the cell cytoplasm and inhibition of HIV-1 infection. Here, we determined that truncated CPSF6 protein forms large higher-order complexes that bind directly to HIV-1 capsid, leading to its disruption. Truncated CPSF6 expression in cells leads to premature capsid uncoating that is detrimental to HIV-1 infection. Our study provides the first direct evidence for an oligomeric nature of truncated CPSF6 and insights into the highly regulated process of HIV-1 capsid uncoating. Copyright © 2018 American Society for Microbiology.

Occurrence of small Hsd plasmids in Salmonella typhi, Shigella boydii, and Escherichia coli.

PubMed Central

Yoshida, Y; Mise, K

1986-01-01

The natural occurrence of small Hsd (host specificity for DNA) plasmids was demonstrated in restriction endonuclease-producing strains of Salmonella typhi, Shigella boydii, and Escherichia coli. The five Hsd plasmids isolated were between 5.0 and 12.2 kilobases long. The copy number of all the Hsd plasmids was high (more than 10 copies per cell). Introduction of these small plasmids into E. coli strain 0 drastically lowered the efficiency of plating of the lambda.0 phages (the efficiency of plating was less than 5 X 10(-5) PFU-1). High restriction endonuclease activities were detected in the Hsd plasmid-positive strains because of the elevated copy numbers of the hsdR+ gene. The advantages of using E. coli strains containing the small Hsd plasmids for purification of type II restriction endonucleases are discussed. Images PMID:3003023

Ultrastructure of the replication sites of positive-strand RNA viruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harak, Christian; Lohmann, Volker, E-mail: volker_lohmann@med.uni-heidelberg.de

2015-05-15

Positive strand RNA viruses replicate in the cytoplasm of infected cells and induce intracellular membranous compartments harboring the sites of viral RNA synthesis. These replication factories are supposed to concentrate the components of the replicase and to shield replication intermediates from the host cell innate immune defense. Virus induced membrane alterations are often generated in coordination with host factors and can be grouped into different morphotypes. Recent advances in conventional and electron microscopy have contributed greatly to our understanding of their biogenesis, but still many questions remain how viral proteins capture membranes and subvert host factors for their need. Inmore » this review, we will discuss different representatives of positive strand RNA viruses and their ways of hijacking cellular membranes to establish replication complexes. We will further focus on host cell factors that are critically involved in formation of these membranes and how they contribute to viral replication. - Highlights: • Positive strand RNA viruses induce massive membrane alterations. • Despite the great diversity, replication complexes share many similarities. • Host factors play a pivotal role in replication complex biogenesis. • Use of the same host factors by several viruses hints to similar functions.« less

Ebola virus host cell entry.

PubMed

Sakurai, Yasuteru

2015-01-01

Ebola virus is an enveloped virus with filamentous structure and causes a severe hemorrhagic fever in human and nonhuman primates. Host cell entry is the first essential step in the viral life cycle, which has been extensively studied as one of the therapeutic targets. A virus factor of cell entry is a surface glycoprotein (GP), which is an only essential viral protein in the step, as well as the unique particle structure. The virus also interacts with a lot of host factors to successfully enter host cells. Ebola virus at first binds to cell surface proteins and internalizes into cells, followed by trafficking through endosomal vesicles to intracellular acidic compartments. There, host proteases process GPs, which can interact with an intracellular receptor. Then, under an appropriate circumstance, viral and endosomal membranes are fused, which is enhanced by major structural changes of GPs, to complete host cell entry. Recently the basic research of Ebola virus infection mechanism has markedly progressed, largely contributed by identification of host factors and detailed structural analyses of GPs. This article highlights the mechanism of Ebola virus host cell entry, including recent findings.

Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

PubMed Central

Kuss, Sharon K.; Mata, Miguel A.; Zhang, Liang; Fontoura, Beatriz M. A.

2013-01-01

Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA) that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses. PMID:23872491

Resolving the infection process reveals striking differences in the contribution of environment, genetics and phylogeny to host-parasite interactions

PubMed Central

2011-01-01

Background Infection processes consist of a sequence of steps, each critical for the interaction between host and parasite. Studies of host-parasite interactions rarely take into account the fact that different steps might be influenced by different factors and might, therefore, make different contributions to shaping coevolution. We designed a new method using the Daphnia magna - Pasteuria ramosa system, one of the rare examples where coevolution has been documented, in order to resolve the steps of the infection and analyse the factors that influence each of them. Results Using the transparent Daphnia hosts and fluorescently-labelled spores of the bacterium P. ramosa, we identified a sequence of infection steps: encounter between parasite and host; activation of parasite dormant spores; attachment of spores to the host; and parasite proliferation inside the host. The chances of encounter had been shown to depend on host genotype and environment. We tested the role of genetic and environmental factors in the newly described activation and attachment steps. Hosts of different genotypes, gender and species were all able to activate endospores of all parasite clones tested in different environments; suggesting that the activation cue is phylogenetically conserved. We next established that parasite attachment occurs onto the host oesophagus independently of host species, gender and environmental conditions. In contrast to spore activation, attachment depended strongly on the combination of host and parasite genotypes. Conclusions Our results show that different steps are influenced by different factors. Host-type-independent spore activation suggests that this step can be ruled out as a major factor in Daphnia-Pasteuria coevolution. On the other hand, we show that the attachment step is crucial for the pronounced genetic specificities of this system. We suggest that this one step can explain host population structure and could be a key force behind coevolutionary cycles. We discuss how different steps can explain different aspects of the coevolutionary dynamics of the system: the properties of the attachment step, explaining the rapid evolution of infectivity and the properties of later parasite proliferation explaining the evolution of virulence. Our study underlines the importance of resolving the infection process in order to better understand host-parasite interactions. PMID:21342515

Immune Ecosystem of Virus-Infected Host Tissues.

PubMed

Maarouf, Mohamed; Rai, Kul Raj; Goraya, Mohsan Ullah; Chen, Ji-Long

2018-05-06

Virus infected host cells serve as a central immune ecological niche during viral infection and replication and stimulate the host immune response via molecular signaling. The viral infection and multiplication process involves complex intracellular molecular interactions between viral components and the host factors. Various types of host cells are also involved to modulate immune factors in delicate and dynamic equilibrium to maintain a balanced immune ecosystem in an infected host tissue. Antiviral host arsenals are equipped to combat or eliminate viral invasion. However, viruses have evolved with strategies to counter against antiviral immunity or hijack cellular machinery to survive inside host tissue for their multiplication. However, host immune systems have also evolved to neutralize the infection; which, in turn, either clears the virus from the infected host or causes immune-mediated host tissue injury. A complex relationship between viral pathogenesis and host antiviral defense could define the immune ecosystem of virus-infected host tissues. Understanding of the molecular mechanism underlying this ecosystem would uncover strategies to modulate host immune function for antiviral therapeutics. This review presents past and present updates of immune-ecological components of virus infected host tissue and explains how viruses subvert the host immune surveillances.

Host and parasite life history interplay to yield divergent population genetic structures in two ectoparasites living on the same bat species.

PubMed

van Schaik, J; Dekeukeleire, D; Kerth, G

2015-05-01

Host-parasite interactions are ubiquitous in nature. However, how parasite population genetic structure is shaped by the interaction between host and parasite life history remains understudied. Studies comparing multiple parasites infecting a single host can be used to investigate how different parasite life history traits interplay with host behaviour and life history. In this study, we used 10 newly developed microsatellite loci to investigate the genetic structure of a parasitic bat fly (Basilia nana). Its host, the Bechstein's bat (Myotis bechsteinii), has a social system and roosting behaviour that restrict opportunities for parasite transmission. We compared fly genetic structure to that of the host and another parasite, the wing-mite, Spinturnix bechsteini. We found little spatial or temporal genetic structure in B. nana, suggesting a large, stable population with frequent genetic exchange between fly populations from different bat colonies. This contrasts sharply with the genetic structure of the wing-mite, which is highly substructured between the same bat colonies as well as temporally unstable. Our results suggest that although host and parasite life history interact to yield similar transmission patterns in both parasite species, the level of gene flow and eventual spatiotemporal genetic stability is differentially affected. This can be explained by the differences in generation time and winter survival between the flies and wing-mites. Our study thus exemplifies that the population genetic structure of parasites on a single host can vary strongly as a result of how their individual life history characteristics interact with host behaviour and life history traits. © 2015 John Wiley & Sons Ltd.

The severity and associated factors of participation restriction among community-dwelling frail older people: an application of the International Classification of Functioning, Disability and Health (WHO-ICF).

PubMed

Liu, Justina Yat Wa

2017-01-31

The International Classification of Functioning, Disability, and Health (WHO-ICF) describes participation restriction as one aspect of disability. Participation restriction refers to health problems that can hinder people's involvement in different life events. It is rational to believe that the prevalence of participation restriction increases among a frail population. However, information about the level of participation restriction among older people, particularly the pre-frail or frail, remains scant. The aim of this study was to identify the prevalence and underlying risk factors associated with participation restriction among community-dwelling frail and pre-frail older people. A cross-section of 299 community-dwelling frail older people with a mean age of 79.5 participated in this study. They had to have been identified as being either pre-frail or frail based on the five common characteristics of the frailty phenotype. Their level of participation restriction was assessed based on the Chinese Reintegration to Nursing Living Index (C-RNLI). All other independent variables were identified and systematically linked to different components in the WHO-ICF framework. Among all participants, 207 (69.2%) were identified as encountering participation restrictions in at least one aspect of their life, with a mean C-RNLI score of 68.3 (SD 19.43). A multivariate regression analysis showed that the participants' status of frailty, self-perceived social status, level of exhibited depressive mood, sleep quality, mobility, level of fear of falling, and physical activity levels had a significant association with participation restriction. When all of the variables, regardless of significance, were included, the factors together explained 67.1% of the variance in the participants' participation restriction. Participation restriction was prevalent among community-dwelling frail older people and was associated with factors across different components in the WHO-ICF. This finding supports the view that participation restriction is multifactorial in nature.

Restrictive vs. non-restrictive composition: a magnetoencephalography study

PubMed Central

Leffel, Timothy; Lauter, Miriam; Westerlund, Masha; Pylkkänen, Liina

2014-01-01

Recent research on the brain mechanisms underlying language processing has implicated the left anterior temporal lobe (LATL) as a central region for the composition of simple phrases. Because these studies typically present their critical stimuli without contextual information, the sensitivity of LATL responses to contextual factors is unknown. In this magnetoencephalography (MEG) study, we employed a simple question-answer paradigm to manipulate whether a prenominal adjective or determiner is interpreted restrictively, i.e., as limiting the set of entities under discussion. Our results show that the LATL is sensitive to restriction, with restrictive composition eliciting higher responses than non-restrictive composition. However, this effect was only observed when the restricting element was a determiner, adjectival stimuli showing the opposite pattern, which we hypothesise to be driven by the special pragmatic properties of non-restrictive adjectives. Overall, our results demonstrate a robust sensitivity of the LATL to high level contextual and potentially also pragmatic factors. PMID:25379512

Earmuff restricts progenitor cell potential by attenuating the competence to respond to self-renewal factors.

PubMed

Janssens, Derek H; Komori, Hideyuki; Grbac, Daniel; Chen, Keng; Koe, Chwee Tat; Wang, Hongyan; Lee, Cheng-Yu

2014-03-01

Despite expressing stem cell self-renewal factors, intermediate progenitor cells possess restricted developmental potential, which allows them to give rise exclusively to differentiated progeny rather than stem cell progeny. Failure to restrict the developmental potential can allow intermediate progenitor cells to revert into aberrant stem cells that might contribute to tumorigenesis. Insight into stable restriction of the developmental potential in intermediate progenitor cells could improve our understanding of the development and growth of tumors, but the mechanisms involved remain largely unknown. Intermediate neural progenitors (INPs), generated by type II neural stem cells (neuroblasts) in fly larval brains, provide an in vivo model for investigating the mechanisms that stably restrict the developmental potential of intermediate progenitor cells. Here, we report that the transcriptional repressor protein Earmuff (Erm) functions temporally after Brain tumor (Brat) and Numb to restrict the developmental potential of uncommitted (immature) INPs. Consistently, endogenous Erm is detected in immature INPs but undetectable in INPs. Erm-dependent restriction of the developmental potential in immature INPs leads to attenuated competence to respond to all known neuroblast self-renewal factors in INPs. We also identified that the BAP chromatin-remodeling complex probably functions cooperatively with Erm to restrict the developmental potential of immature INPs. Together, these data led us to conclude that the Erm-BAP-dependent mechanism stably restricts the developmental potential of immature INPs by attenuating their genomic responses to stem cell self-renewal factors. We propose that restriction of developmental potential by the Erm-BAP-dependent mechanism functionally distinguishes intermediate progenitor cells from stem cells, ensuring the generation of differentiated cells and preventing the formation of progenitor cell-derived tumor-initiating stem cells.

Fasting or caloric restriction for healthy aging.

PubMed

Anton, Stephen; Leeuwenburgh, Christiaan

2013-10-01

Aging is associated with a host of biological changes that contribute to a progressive decline in cognitive and physical function, ultimately leading to a loss of independence, and increased risk of mortality. To date, prolonged caloric restriction (i.e., a reduction in caloric intake without malnutrition) is the only non-genetic intervention that has consistently been found to extend both mean and maximal life span across a variety of species. Most individuals have difficulty sustaining prolonged caloric restriction, which has led to a search for alternative approaches that can produce similar to benefits as caloric restriction. A growing body of evidence indicates that fasting periods and intermittent fasting regimens in particular can trigger similar biological pathways as caloric restriction. For this reason, there is increasing scientific interest in further exploring the biological and metabolic effects of intermittent fasting periods, as well as whether long-term compliance may be improved by this type of dietary approach. This special will highlight the latest scientific findings related to the effects of both caloric restriction and intermittent fasting across various species including yeast, fruit flies, worms, rodents, primates, and humans. A specific emphasis is placed on translational research with findings from basic bench to bedside reviewed and practical clinical implications discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

HLA-B*27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T cell epitope.

PubMed

Nitschke, Katja; Barriga, Alejandro; Schmidt, Julia; Timm, Jörg; Viazov, Sergei; Kuntzen, Thomas; Kim, Arthur Y; Lauer, Georg M; Allen, Todd M; Gaudieri, Silvana; Rauch, Andri; Lange, Christian M; Sarrazin, Christoph; Eiermann, Thomas; Sidney, John; Sette, Alessandro; Thimme, Robert; López, Daniel; Neumann-Haefelin, Christoph

2014-01-01

HLA-B*27 is associated with spontaneous HCV genotype 1 clearance. HLA-B*27-restricted CD8+ T cells target three NS5B epitopes. Two of these epitopes are dominantly targeted in the majority of HLA-B*27+ patients. In chronic infection, viral escape occurs consistently in these two epitopes. The third epitope (NS5B2820) was dominantly targeted in an acutely infected patient. This was in contrast, however, to the lack of recognition and viral escape in the large majority of HLA-B*27+ patients. Here, we set out to determine the host factors contributing to selective targeting of this epitope. Four-digit HLA class I typing and viral sequence analyses were performed in 78 HLA-B*27+ patients with chronic HCV genotype 1 infection. CD8+ T cell analyses were performed in a subset of patients. In addition, HLA/peptide affinity was compared for HLA-B*27:02 and 05. The NS5B2820 epitope is only restricted by the HLA-B*27 subtype HLA-B*27:02 (that is frequent in Mediterranean populations), but not by the prototype HLA-B*27 subtype B*27:05. Indeed, the epitope is very dominant in HLA-B*27:02+ patients and is associated with viral escape mutations at the anchor position for HLA-binding in 12 out of 13 HLA-B*27:02+ chronically infected patients. The NS5B2820 epitope is immunodominant in the context of HLA-B*27:02, but is not restricted by other HLA-B*27 subtypes. This finding suggests an important role of HLA subtypes in the restriction of HCV-specific CD8+ responses. With minor HLA subtypes covering up to 39% of specific populations, these findings may have important implications for the selection of epitopes for global vaccines. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Fitness Impact of Obligate Intranuclear Bacterial Symbionts Depends on Host Growth Phase

PubMed Central

Bella, Chiara; Koehler, Lars; Grosser, Katrin; Berendonk, Thomas U.; Petroni, Giulio; Schrallhammer, Martina

2016-01-01

According to text book definition, parasites reduce the fitness of their hosts whereas mutualists provide benefits. But biotic and abiotic factors influence symbiotic interactions, thus under certain circumstances parasites can provide benefits and mutualists can harm their host. Here we addressed the question which intrinsic biotic factors shape a symbiosis and are crucial for the outcome of the interaction between the obligate intranuclear bacterium Holospora caryophila (Alphaproteobacteria; Rickettsiales) and its unicellular eukaryotic host Paramecium biaurelia (Alveolata; Ciliophora). The virulence of H. caryophila, i.e., the negative fitness effect on host division and cell number, was determined by growth assays of several P. biaurelia strains. The performances of genetically identical lines either infected with H. caryophila or symbiont-free were compared. Following factors were considered as potentially influencing the outcome of the interaction: (1) host strain, (2) parasite strain, and (3) growth phases of the host. All three factors revealed a strong effect on the symbiosis. In presence of H. caryophila, the Paramecium density in the stationary growth phase decreased. Conversely, a positive effect of the bacteria during the exponential phase was observed for several host × parasite combinations resulting in an increased growth rate of infected P. biaurelia. Furthermore, the fitness impact of the tested endosymbionts on different P. biaurelia lines was not only dependent on one of the two involved strains but distinct for the specific combination. Depending on the current host growth phase, the presence of H. caryophila can be harmful or advantageous for P. biaurelia. Thus, under the tested experimental conditions, the symbionts can switch from the provision of benefits to the exploitation of host resources within the same host population and a time-span of less than 6 days. PMID:28066397

Mechanisms involved in parasitic castration: in vitro effects of the trematode Prosorhynchus squamatus on the gametogenesis and the nutrient storage metabolism of the marine bivalve mollusc Mytilus edulis.

PubMed

Coustau, C; Renaud, F; Delay, B; Robbins, I; Mathieu, M

1991-07-01

The mechanisms involved in the parasitic castration of the marine mussel Mytilus edulis by the trematode parasite Prosorhynchus squamatus Odhner, 1905, have been investigated in vitro with two bioassays employing dissociated host tissues. There is no conclusive evidence that P. squamatus affects the secretion of two host neuroendocrine factors, viz., gonial mitosis-stimulating factor and glycogen mobilization hormone, involved in the gametogenesis/nutrient storage cycles of the mussel. In contrast, extracts of P. squamatus sporocysts and cercariae significantly stimulated glycogen mobilization in host glycogen cells and strongly inhibited host gonial mitosis. A gonial mitosis-inhibiting factor (GMIF) was found in the hemolymph of parasitized mussels. The existence of an endogenous GMIF in mantle tissue of uninfected mussels has been demonstrated. This factor appeared to be secreted into the hemolymph during the period of sexual maturity. Whether the parasite acts directly on the host gonia, or by provoking the liberation of this endogenous GMIF, has yet to be ascertained. It would appear, however, that the parasite acts directly on host glycogen cells.

The interactions of intracellular Protista and their host cells, with special reference to heterotrophic organisms.

PubMed

Bannister, L H

1979-04-11

Intracellular genera are found in all the major groups of Protista, but are particularly common among the dinoflagellates, trypanosomatid zooflagellates and suctorian ciliates; the Sporozoa are nearly all intracellular at some stage of their life, and the Microspora entirely so. Intracellular forms can dwell in the nucleus, within phagosomal or other vacuoles or may lie free in the hyaloplasm of their host cells. Organisms tend to select their hosts from a restricted taxonomic range although there are some notable exceptions. There is also great variation in the types of host cell inhabited. There are various reasons for both host and cell selectivity including recognition phenomena at the cell surfaces. Invasion of host cells is usually preceded by surface interactions with the invader. Some organisms depend upon phagocytosis for entry, but others induce host cells to engulf them by non-phagocytic means or invade by microinjection through the host plasma membrane. Protista avoid lysosomal destruction by their resistance to enzyme attack, by surrounding themselves with lysosome-inhibiting vacuoles, by escaping from the phagosomal system into the hyaloplasm and by choosing host cells which lack lysosomes. Nutrition of intracellular heterotrophic organisms involves some degree of competition with the host cell's metabolism as well as erosion of host cell cytoplasm. In Plasmodium infections, red cells are made more permeable to required nutrients by the action of the parasite on the host cell membrane. The parasite is often dependent upon the host cell for complex nutrients which it cannot synthesize for itself. Intracellular forms often profoundly modify the structure and metabolism of the host cell or interfere with its growth and multiplication. This may result in the final lysis of the host cell at the end of the intracellular phase or before the infection of other cells. Certain types of intracellular organisms may have arisen initially as forms attached to the cell surface of digestive or other organs, but the intracellular habit appears to have arisen independently in several groups of Protista.

Variants of early-onset restrictive eating disturbances in middle childhood.

PubMed

Kurz, Susanne; van Dyck, Zoé; Dremmel, Daniela; Munsch, Simone; Hilbert, Anja

2016-01-01

This study sought to determine the factor structure of the newly developed self-report screening questionnaire Eating Disturbances in Youth-Questionnaire (EDY-Q) as well as to report the distribution of variants of early-onset restrictive eating disturbances characteristic of avoidant/restrictive food intake disorder (ARFID) in a middle childhood population sample. Using the EDY-Q, a total of 1,444 children aged 8-13 years were screened in elementary schools in Switzerland via self-report. The factor analysis of the 12 items covering ARFID related symptoms was performed using a principal component analysis (PCA). The PCA showed a four factor solution, with clear allocation to the scales covering three variants of early-onset restrictive eating disturbances and weight problems. Inadequate overall food intake was reported by 19.3% of the children, a limited accepted amount of food by 26.1%, and food avoidance based on a specific underlying fear by 5.0%. The postulated factor structure of the EDY-Q was confirmed, further supporting the existence of distinct variants of early-onset restrictive eating disturbances. Avoidant/restrictive eating behavior seems to be a common experience in middle childhood, but results have to be confirmed using validated interviews. © 2015 Wiley Periodicals, Inc.

Acting on Actin: Rac and Rho Played by Yersinia.

PubMed

Aepfelbacher, Martin; Wolters, Manuel

2017-01-01

Pathogenic bacteria of the genus Yersinia include Y. pestis-the agent of plaque-and two enteropathogens, Y. enterocolitica, and Y. pseudotuberculosis. These pathogens have developed an array of virulence factors aimed at manipulating Rho GTP-binding proteins and the actin cytoskeleton in host cells to cross the intestinal barrier and suppress the immune system. Yersinia virulence factors include outer membrane proteins triggering cell invasion by binding to integrins, effector proteins injected into host cells to manipulate Rho protein functions and a Rho protein-activating exotoxin. Here, we present an overview of how Yersinia and host factors are integrated in a regulatory network that orchestrates the subversion of host defense.

Myristoylated PreS1-domain of the hepatitis B virus L-protein mediates specific binding to differentiated hepatocytes.

PubMed

Meier, Anja; Mehrle, Stefan; Weiss, Thomas S; Mier, Walter; Urban, Stephan

2013-07-01

Chronic infection with the human hepatitis B virus (HBV) is a global health problem and a main cause of progressive liver diseases. HBV exhibits a narrow host range, replicating primarily in hepatocytes. Both host and hepatocyte specificity presumably involve specific receptor interactions on the target cell; however, direct evidence for this hypothesis is missing. Following the observation that HBV entry is specifically blocked by L-protein-derived preS1-lipopeptides, we visualized specific HBV receptor/ligand complexes on hepatic cells and quantified the turnover kinetics. Using fluorescein isothiocyanate-labeled, myristoylated HBV preS1-peptides we demonstrate (1) the presence of a highly specific HBV receptor on the plasma membrane of HBV-susceptible primary human and tupaia hepatocytes and HepaRG cells but also on hepatocytes from the nonsusceptible species mouse, rat, rabbit and dog; (2) the requirement of a differentiated state of the hepatocyte for specific preS1-binding; (3) the lack of detectable amounts of the receptor on HepG2 and HuH7 cells; (4) a slow receptor turnover at the hepatocyte membrane; and (5) an association of the receptor with actin microfilaments. The presence of the preS1-receptor in primary hepatocytes from some non-HBV-susceptible species indicates that the lack of susceptibility of these cells is owed to a postbinding step. These findings suggest that HBV hepatotropism is mediated by the highly selective expression of a yet unknown receptor* on differentiated hepatocytes, while species specificity of the HBV infection requires selective downstream events, e.g., the presence of host dependency or the absence of host restriction factors. The criteria defined here will allow narrowing down reasonable receptor candidates and provide a binding assay for HBV-receptor expression screens in hepatic cells. Copyright © 2012 American Association for the Study of Liver Diseases.

In situ Occurrence, Prevalence and Dynamics of Parvilucifera Parasitoids during Recurrent Blooms of the Toxic Dinoflagellate Alexandrium minutum

PubMed Central

Alacid, Elisabet; Reñé, Albert; Camp, Jordi; Garcés, Esther

2017-01-01

Dinoflagellate blooms are natural phenomena that often occur in coastal areas, which in addition to their large number of nutrient-rich sites are characterized by highly restricted hydrodynamics within bays, marinas, enclosed beaches, and harbors. In these areas, massive proliferations of dinoflagellates have harmful effects on humans and the ecosystem. However, the high cell density reached during blooms make them vulnerable to parasitic infections. Under laboratory conditions parasitoids are able to exterminate an entire host population. In nature, Parvilucifera parasitoids infect the toxic dinoflagellate Alexandrium minutum during bloom conditions but their prevalence and impact remain unexplored. In this study, we evaluated the in situ occurrence, prevalence, and dynamics of Parvilucifera parasitoids during recurrent blooms of A. minutum in a confined site in the NW Mediterranean Sea as well as the contribution of parasitism to bloom termination. Parvilucifera parasitoids were recurrently detected from 2009 to 2013, during seasonal outbreaks of A. minutum. Parasitic infections in surface waters occurred after the abundance of A. minutum reached 104–105 cells L−1, suggesting a density threshold beyond which Parvilucifera transmission is enhanced and the number of infected cells increases. Moreover, host and parasitoid abundances were not in phase. Instead, there was a lag between maximum A. minutum and Parvilucifera densities, indicative of a delayed density-dependent response of the parasitoid to host abundances, similar to the temporal dynamics of predator-prey interactions. The highest parasitoid prevalence was reached after a peak in host abundance and coincided with the decay phase of the bloom, when a maximum of 38% of the A. minutum population was infected. According to our estimates, Parvilucifera infections accounted for 5–18% of the total observed A. minutum mortality, which suggested that the contribution of parasitism to bloom termination is similar to that of other biological factors, such as encystment and grazing. PMID:28912757

Stage of perinatal development regulates skeletal muscle mitochondrial biogenesis and myogenic regulatory factor genes with little impact of growth restriction or cross-fostering.

PubMed

Laker, R C; Wadley, G D; McConell, G K; Wlodek, M E

2012-02-01

Foetal growth restriction impairs skeletal muscle development and adult muscle mitochondrial biogenesis. We hypothesized that key genes involved in muscle development and mitochondrial biogenesis would be altered following uteroplacental insufficiency in rat pups, and improving postnatal nutrition by cross-fostering would ameliorate these deficits. Bilateral uterine vessel ligation (Restricted) or sham (Control) surgery was performed on day 18 of gestation. Males and females were investigated at day 20 of gestation (E20), 1 (PN1), 7 (PN7) and 35 (PN35) days postnatally. A separate cohort of Control and Restricted pups were cross-fostered onto a different Control or Restricted mother and examined at PN7. In both sexes, peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), cytochrome c oxidase subunits 3 and 4 (COX III and IV) and myogenic regulatory factor 4 expression increased from late gestation to postnatal life, whereas mitochondrial transcription factor A, myogenic differentiation 1 (MyoD), myogenin and insulin-like growth factor I (IGF-I) decreased. Foetal growth restriction increased MyoD mRNA in females at PN7, whereas in males IGF-I mRNA was higher at E20 and PN1. Cross-fostering Restricted pups onto a Control mother significantly increased COX III mRNA in males and COX IV mRNA in both sexes above controls with little effect on other genes. Developmental age appears to be a major factor regulating skeletal muscle mitochondrial and developmental genes, with growth restriction and cross-fostering having only subtle effects. It therefore appears that reductions in adult mitochondrial biogenesis markers likely develop after weaning.

Toward Understanding Phage:Host Interactions in the Rumen; Complete Genome Sequences of Lytic Phages Infecting Rumen Bacteria

PubMed Central

Gilbert, Rosalind A.; Kelly, William J.; Altermann, Eric; Leahy, Sinead C.; Minchin, Catherine; Ouwerkerk, Diane; Klieve, Athol V.

2017-01-01

The rumen is known to harbor dense populations of bacteriophages (phages) predicted to be capable of infecting a diverse range of rumen bacteria. While bacterial genome sequencing projects are revealing the presence of phages which can integrate their DNA into the genome of their host to form stable, lysogenic associations, little is known of the genetics of phages which utilize lytic replication. These phages infect and replicate within the host, culminating in host lysis, and the release of progeny phage particles. While lytic phages for rumen bacteria have been previously isolated, their genomes have remained largely uncharacterized. Here we report the first complete genome sequences of lytic phage isolates specifically infecting three genera of rumen bacteria: Bacteroides, Ruminococcus, and Streptococcus. All phages were classified within the viral order Caudovirales and include two phage morphotypes, representative of the Siphoviridae and Podoviridae families. The phage genomes displayed modular organization and conserved viral genes were identified which enabled further classification and determination of closest phage relatives. Co-examination of bacterial host genomes led to the identification of several genes responsible for modulating phage:host interactions, including CRISPR/Cas elements and restriction-modification phage defense systems. These findings provide new genetic information and insights into how lytic phages may interact with bacteria of the rumen microbiome. PMID:29259581

Host and ecology both play a role in shaping distribution of digenean parasites of New Zealand whelks (Gastropoda: Buccinidae: Cominella).

PubMed

Donald, Kirsten M; Spencer, Hamish G

2016-08-01

Digenean parasites infecting four Cominella whelk species (C. glandiformis, C. adspersa, C. maculosa and C. virgata), which inhabit New Zealand's intertidal zone, were analysed using molecular techniques. Mitochondrial 16S and cytochrome oxidase 1 (COI) and nuclear rDNA ITS1 sequences were used to infer phylogenetic relationships amongst digenea. Host species were parasitized by a diverse range of digenea (Platyhelminthes, Trematoda), representing seven families: Echinostomatidae, Opecoelidae, Microphallidae, Strigeidae and three, as yet, undetermined families A, B and C. Each parasite family infected between one and three host whelk species, and infection levels were typically low (average infection rates ranged from 1·4 to 3·6%). Host specificity ranged from highly species-specific amongst the echinostomes, which were only ever observed infecting C. glandiformis, to the more generalist opecoelids and strigeids, which were capable of infecting three out of four of the Cominella species analysed. Digeneans displayed a highly variable geographic range; for example, echinostomes had a large geographic range stretching the length of New Zealand, from Northland to Otago, whereas Family B parasites were restricted to fairly small areas of the North Island. Our results add to a growing body of research identifying wide ranges in both host specificity and geographic range amongst intertidal, multi-host parasite systems.

Intestinal parasites of the Arctic fox in relation to the abundance and distribution of intermediate hosts.

PubMed

Stien, A; Voutilainen, L; Haukisalmi, V; Fuglei, E; Mørk, T; Yoccoz, N G; Ims, R A; Henttonen, H

2010-01-01

The intestinal parasite community of Arctic foxes (Vulpes lagopus) on the Svalbard archipelago in the High Arctic was investigated in relation to the abundance and distribution of intermediate hosts. Five species of cestodes (Echinococcus multilocularis, Taenia crassiceps, Taenia polyacantha, Taenia krabbei and Diphyllobothrium sp.), ascaridoid nematodes and one unidentified acanthocephalan species were found. The cestodes E. multilocularis, T. crassiceps and T. polyacantha all showed a decreasing prevalence in the fox population with increasing distance from their spatially restricted intermediate host population of sibling voles (Microtus levis). In addition, the prevalence of E. multilocularis in a sample from the vole population was directly related to the local vole abundance. The cestode T. krabbei uses reindeer as intermediate host, and its prevalence in female foxes was positively related to the density of reindeer (Rangifer tarandus platyrhyncus). Finally, the prevalence of the ascaridoid nematodes also decreased with increasing distance from the vole population, a finding that is consistent with the idea that voles are involved in transmission, most likely as paratenic hosts. The prevalence of the remaining species (Diphyllobothrium sp. and an unidentified acanthocephalan) was very low. We conclude that the distribution and abundance of intermediate host structure the gastrointestinal parasite community of the Arctic fox on the Svalbard archipelago.

Effects of diet and host access on fecundity and lifespan in two fruit fly species with different life history patterns

PubMed Central

Harwood, James F.; Chen, Kehui; Müller, Hans-Georg; Wang, Jane-Ling; Vargas, Roger I.; Carey, James R.

2013-01-01

The reproductive ability of female tephritids can be limited and prevented by denying access to host plants and restricting the dietary precursors of vitellogenesis. The mechanisms underlying the delayed egg production in each case are initiated by different physiological processes that are anticipated to have dissimilar effects on lifespan and reproductive ability later in life. The egg laying abilities of laboratory reared females of the Mediterranean fruit fly (Ceratitis capitata Wiedmann) and melon fly (Bactrocera cucurbitae Coquillett) from Hawaii are delayed or suppressed by limiting access to host fruits and dietary protein. In each case, this is expected to prevent the loss of lifespan associated with reproduction until protein or hosts are introduced. Two trends are observed in each species: Firstly, access to protein at eclosion leads to a greater probability of survival and higher reproductive ability than if it is delayed, and secondly, that delayed host access reduces lifetime reproductive ability without improving life expectancy. When host access and protein availability are delayed, the rate of reproductive senescence is reduced in the medfly, whereas the rate of reproductive senescence is generally increased in the melon fly. Overall, delaying reproduction lowers the fitness of females by constraining their fecundity for the remainder of the lifespan without extending the lifespan. PMID:23483775

Host specificity and coevolution of Flavobacteriaceae endosymbionts within the siphonous green seaweed Bryopsis.

PubMed

Hollants, Joke; Leliaert, Frederik; Verbruggen, Heroen; De Clerck, Olivier; Willems, Anne

2013-06-01

The siphonous green seaweed Bryopsis harbors complex intracellular bacterial communities. Previous studies demonstrated that certain species form close, obligate associations with Flavobacteriaceae. A predominant imprint of host evolutionary history on the presence of these bacteria suggests a highly specialized association. In this study we elaborate on previous results by expanding the taxon sampling and testing for host-symbiont coevolution Therefore, we optimized a PCR protocol to directly and specifically amplify Flavobacteriaceae endosymbiont 16S rRNA gene sequences, which allowed us to screen a large number of algal samples without the need for cultivation or surface sterilization. We analyzed 146 Bryopsis samples, and 92 additional samples belonging to the Bryopsidales and other orders within the class Ulvophyceae. Results indicate that the Flavobacteriaceae endosymbionts are restricted to Bryopsis, and only occur within specific, warm-temperate and tropical clades of the genus. Statistical analyses (AMOVA) demonstrate a significant non-random host-symbiont association. Comparison of bacterial 16S rRNA and Bryopsis rbcL phylogenies, however, reveal complex host-symbiont evolutionary associations, whereby closely related hosts predominantly harbor genetically similar endosymbionts. Bacterial genotypes are rarely confined to a single Bryopsis species and most Bryopsis species harbored several Flavobacteriaceae, obscuring a clear pattern of coevolution. Copyright © 2013 Elsevier Inc. All rights reserved.

7 CFR 319.77-4 - Conditions for the importation of regulated articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Host Material from Canada § 319.77-4 Conditions for the importation of regulated articles. (a) Trees and shrubs. 1 (1) Trees without roots (e.g., Christmas trees), trees with roots, and shrubs with roots... restriction under this subpart if they: 1 Trees and shrubs from Canada may be subject to additional...

Special Operations Forces During the Dhofar Insurgency and in Afghanistan: A Comparative Study for German Special Operations Forces

DTIC Science & Technology

2011-04-28

rebels’ communist atheism formed unity among the counterinsurgents at the tactical level. The British SOF and the host nation’s indigenous forces...government that first had to be established and now develops its legitimacy. The communist atheism and the Sultan’s restrictive Media campaign

Association of the host immune response with protection using a live attenuated African swine fever virus model

USDA-ARS?s Scientific Manuscript database

African swine fever (ASF) is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, African Swine Fever Virus (ASFV). There is no vaccine to prevent the disease and current control measures are limited to culling and restricted animal movement. Swine infected with attenuated st...

75 FR 27672 - Restrictions on Railroad Operating Employees' Use of Cellular Telephones and Other Electronic...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-18

... by any of the following methods: Federal eRulemaking Portal: Go to http://www.Regulations.gov... while driving. In addition to hosting the Summit, DOT has reviewed recent research and has decided to... conclusions with respect to the involvement of driver distraction in causing a crash. A 2008 research paper...

Can butterflies evade fire? Pupa location and heat tolerance in fire prone habitats of Florida

USDA-ARS?s Scientific Manuscript database

The imperiled frosted elfin butterfly, Callophrys irus Godart, is restricted to frequently disturbed habitats where its larval host plants, Lupinus perennis L. and Baptisia tinctoria (L.) R. Br. occur. C. irus pupae are noted to reside in both leaf litter and soil, which may allow them to escape dir...

7 CFR 319.77-4 - Conditions for the importation of regulated articles.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Host Material from Canada § 319.77-4 Conditions for the importation of regulated articles. (a) Trees and shrubs. 1 (1) Trees without roots (e.g., Christmas trees), trees with roots, and shrubs with roots... restriction under this subpart if they: 1 Trees and shrubs from Canada may be subject to additional...

7 CFR 319.77-4 - Conditions for the importation of regulated articles.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Host Material from Canada § 319.77-4 Conditions for the importation of regulated articles. (a) Trees and shrubs. 1 (1) Trees without roots (e.g., Christmas trees), trees with roots, and shrubs with roots... restriction under this subpart if they: 1 Trees and shrubs from Canada may be subject to additional...