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Sample records for pathogenic virus infection

  1. Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome

    PubMed Central

    Handley, Scott; Thackray, Larissa B.; Zhao, Guoyan; Presti, Rachel; Miller, Andrew; Droit, Lindsay; Abbink, Peter; Maxfield, Lori F.; Kambal, Amal; Duan, Erning; Stanley, Kelly; Kramer, Joshua; Macri, Sheila C.; Permar, Sallie R.; Schmitz, Joern E.; Mansfield, Keith; Brenchley, Jason M.; Veazey, Ronald S.; Stappenbeck, Thaddeus S.; Wang, David; Barouch, Dan H.; Virgin, Herbert W.

    2012-01-01

    SUMMARY Pathogenic simian immunodeficiency virus (SIV) infection is associated with enteropathy which likely contributes to AIDS progression. To identify candidate etiologies for AIDS enteropathy, we used next generation sequencing to define the enteric virome during SIV infection in nonhuman primates. Pathogenic, but not non-pathogenic, SIV infection was associated with significant expansion of the enteric virome. We identified at least 32 previously undescribed enteric viruses during pathogenic SIV infection and confirmed their presence using viral culture and PCR testing. We detected unsuspected mucosal adenovirus infection associated with enteritis as well as parvovirus viremia in animals with advanced AIDS, indicating the pathogenic potential of SIV-associated expansion of the enteric virome. No association between pathogenic SIV infection and the family-level taxonomy of enteric bacteria was detected. Thus, enteric viral infections may contribute to AIDS enteropathy and disease progression. These findings underline the importance of metagenomic analysis of the virome for understanding AIDS pathogenesis. PMID:23063120

  2. Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

    PubMed

    Greenwood, Edward J D; Schmidt, Fabian; Kondova, Ivanela; Niphuis, Henk; Hodara, Vida L; Clissold, Leah; McLay, Kirsten; Guerra, Bernadette; Redrobe, Sharon; Giavedoni, Luis D; Lanford, Robert E; Murthy, Krishna K; Rouet, François; Heeney, Jonathan L

    2015-09-01

    The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.

  3. Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections

    PubMed Central

    Greenwood, Edward J. D.; Schmidt, Fabian; Kondova, Ivanela; Niphuis, Henk; Hodara, Vida L.; Clissold, Leah; McLay, Kirsten; Guerra, Bernadette; Redrobe, Sharon; Giavedoni, Luis D.; Lanford, Robert E.; Murthy, Krishna K.; Rouet, François; Heeney, Jonathan L.

    2015-01-01

    The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in ‘natural host’ species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections. PMID:26360709

  4. High doses of highly pathogenic avian influenza virus in chicken meat are required to infect ferrets

    PubMed Central

    2014-01-01

    High pathogenicity avian influenza viruses (HPAIV) have caused fatal infections in mammals through consumption of infected bird carcasses or meat, but scarce information exists on the dose of virus required and the diversity of HPAIV subtypes involved. Ferrets were exposed to different HPAIV (H5 and H7 subtypes) through consumption of infected chicken meat. The dose of virus needed to infect ferrets through consumption was much higher than via respiratory exposure and varied with the virus strain. In addition, H5N1 HPAIV produced higher titers in the meat of infected chickens and more easily infected ferrets than the H7N3 or H7N7 HPAIV. PMID:24894438

  5. Human Infection with Highly Pathogenic A(H7N7) Avian Influenza Virus, Italy, 2013

    PubMed Central

    Rossini, Giada; Facchini, Marzia; Vaccari, Gabriele; Di Trani, Livia; Di Martino, Angela; Gaibani, Paolo; Vocale, Caterina; Cattoli, Giovanni; Bennett, Michael; McCauley, John W.; Rezza, Giovanni; Moro, Maria Luisa; Rangoni, Roberto; Finarelli, Alba Carola; Landini, Maria Paola; Castrucci, Maria Rita; Donatelli, Isabella

    2014-01-01

    During an influenza A(H7N7) virus outbreak among poultry in Italy during August–September 2013, infection with a highly pathogenic A(H7N7) avian influenza virus was diagnosed for 3 poultry workers with conjunctivitis. Genetic analyses revealed that the viruses from the humans were closely related to those from chickens on affected farms. PMID:25271444

  6. Highly Pathogenic Avian Influenza Virus Infection of Mallards with Homo- and Heterosubtypic Immunity Induced by Low Pathogenic Avian Influenza Viruses

    PubMed Central

    Fereidouni, Sasan R.; Starick, Elke; Beer, Martin; Wilking, Hendrik; Kalthoff, Donata; Grund, Christian; Häuslaigner, Rafaela; Breithaupt, Angele; Lange, Elke; Harder, Timm C.

    2009-01-01

    The potential role of wild birds as carriers of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 is still a matter of debate. Consecutive or simultaneous infections with different subtypes of influenza viruses of low pathogenicity (LPAIV) are very common in wild duck populations. To better understand the epidemiology and pathogenesis of HPAIV H5N1 infections in natural ecosystems, we investigated the influence of prior infection of mallards with homo- (H5N2) and heterosubtypic (H4N6) LPAIV on exposure to HPAIV H5N1. In mallards with homosubtypic immunity induced by LPAIV infection, clinical disease was absent and shedding of HPAIV from respiratory and intestinal tracts was grossly reduced compared to the heterosubtypic and control groups (mean GEC/100 µl at 3 dpi: 3.0×102 vs. 2.3×104 vs. 8.7×104; p<0.05). Heterosubtypic immunity induced by an H4N6 infection mediated a similar but less pronounced effect. We conclude that the epidemiology of HPAIV H5N1 in mallards and probably other aquatic wild bird species is massively influenced by interfering immunity induced by prior homo- and heterosubtypic LPAIV infections. PMID:19693268

  7. Protective and Pathogenic Responses to Chikungunya Virus Infection

    PubMed Central

    Long, Kristin M.; Heise, Mark T.

    2015-01-01

    Chikungunya virus (CHIKV) is an arbovirus responsible for causing epidemic outbreaks of human disease characterized by painful and often debilitating arthralgia. Recently CHIKV has moved into the Caribbean and the Americas resulting in massive outbreaks in naïve human populations. Given the importance of CHIKV as an emerging disease, a significant amount of effort has gone into interpreting the virus-host interactions that contribute to protection or virus-induced pathology following CHIKV infection, with the long term goal of using this information to develop new therapies or safe and effective anti-CHIKV vaccines. This work has made it clear that numerous distinct host responses are involved in the response to CHIKV infection, where some aspects of the host innate and adaptive immune response protect from or limit virus-induced disease, while other pathways actually exacerbate the virus-induced disease process. This review will discuss mechanisms that have been identified as playing a role in the host response to CHIKV infection and illustrate the importance of carefully evaluating these responses to determine whether they play a protective or pathologic role during CHIKV infection. PMID:26366337

  8. Within-Host Models of High and Low Pathogenic Influenza Virus Infections: The Role of Macrophages

    PubMed Central

    Pawelek, Kasia A.; Dor, Daniel; Salmeron, Cristian; Handel, Andreas

    2016-01-01

    The World Health Organization identifies influenza as a major public health problem. While the strains commonly circulating in humans usually do not cause severe pathogenicity in healthy adults, some strains that have infected humans, such as H5N1, can cause high morbidity and mortality. Based on the severity of the disease, influenza viruses are sometimes categorized as either being highly pathogenic (HP) or having low pathogenicity (LP). The reasons why some strains are LP and others HP are not fully understood. While there are likely multiple mechanisms of interaction between the virus and the immune response that determine LP versus HP outcomes, we focus here on one component, namely macrophages (MP). There is some evidence that MP may both help fight the infection and become productively infected with HP influenza viruses. We developed mathematical models for influenza infections which explicitly included the dynamics and action of MP. We fit these models to viral load and macrophage count data from experimental infections of mice with LP and HP strains. Our results suggest that MP may not only help fight an influenza infection but may contribute to virus production in infections with HP viruses. We also explored the impact of combination therapies with antivirals and anti-inflammatory drugs on HP infections. Our study suggests a possible mechanism of MP in determining HP versus LP outcomes, and how different interventions might affect infection dynamics. PMID:26918620

  9. Previous infection with a mesogenic strain of Newcastle disease virus affects infection with highly pathogenic avian influenza viruses in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) and Newcastle disease virus (NDV) are two of the most important viruses affecting poultry worldwide, but little is known on the interactions between these two viruses when infecting birds. In a previous study we found that infection of chickens with a mesogenic strain of...

  10. Transcriptome Analysis of Bombyx mori Larval Midgut during Persistent and Pathogenic Cytoplasmic Polyhedrosis Virus Infection

    PubMed Central

    Kolliopoulou, Anna; Van Nieuwerburgh, Filip; Stravopodis, Dimitrios J.; Deforce, Dieter; Swevers, Luc; Smagghe, Guy

    2015-01-01

    Many insects can be persistently infected with viruses but do not show any obvious adverse effects with respect to physiology, development or reproduction. Here, Bombyx mori strain Daizo, persistently infected with cytoplasmic polyhedrosis virus (BmCPV), was used to study the host’s transcriptional response after pathogenic infection with the same virus in midgut tissue of larvae persistently and pathogenically infected as 2nd and 4th instars. Next generation sequencing revealed that from 13,769 expressed genes, 167 were upregulated and 141 downregulated in both larval instars following pathogenic infection. Several genes that could possibly be involved in B. mori immune response against BmCPV or that may be induced by the virus in order to increase infectivity were identified, whereas classification of differentially expressed transcripts (confirmed by qRT-PCR) resulted in gene categories related to physical barriers, immune responses, proteolytic / metabolic enzymes, heat-shock proteins, hormonal signaling and uncharacterized proteins. Comparison of our data with the available literature (pathogenic infection of persistently vs. non-persistently infected larvae) unveiled various similarities of response in both cases, which suggests that pre-existing persistent infection does not affect in a major way the transcriptome response against pathogenic infection. To investigate the possible host’s RNAi response against BmCPV challenge, the differential expression of RNAi-related genes and the accumulation of viral small RNAs (vsRNAs) were studied. During pathogenic infection, siRNA-like traces like the 2-fold up-regulation of the core RNAi genes Ago-2 and Dcr-2 as well as a peak of 20 nt small RNAs were observed. Interestingly, vsRNAs of the same size were detected at lower rates in persistently infected larvae. Collectively, our data provide an initial assessment of the relative significance of persistent infection of silkworm larvae on the host response following

  11. Effect of Infection with a Mesogenic Strain of Newcastle Disease Virus on Infection with Highly Pathogenic Avian Influenza Virus in Chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known on the interactions between avian influenza virus (AIV) and Newcastle disease virus (NDV) when coinfecting the same poultry host. In a previous study we found that infection of chickens with a mesogenic strain of NDV (mNDV) can reduce highly pathogenic AIV (HPAIV) replication, clinic...

  12. Pathogenicity of different rabies virus variants inversely correlates with apoptosis and rabies virus glycoprotein expression in infected primary neuron cultures.

    PubMed

    Morimoto, K; Hooper, D C; Spitsin, S; Koprowski, H; Dietzschold, B

    1999-01-01

    The mouse-adapted rabies virus strain CVS-24 has stable variants, CVS-B2c and CVS-N2c, which differ greatly in their pathogenicity for normal adult mice and in their ability to infect nonneuronal cells. The glycoprotein (G protein), which has previously been implicated in rabies virus pathogenicity, shows substantial structural differences between these variants. Although prior studies have identified antigenic site III of the G protein as the major pathogenicity determinant, CVS-B2c and CVS-N2c do not vary at this site. The possibility that pathogenicity is inversely related to G protein expression levels is suggested by the finding that CVS-B2c, the less pathogenic variant, expresses at least fourfold-higher levels of G protein than CVS-N2c in infected neurons. Although there is some difference between CVS-B2c- and CVS-N2c-infected neurons in G protein mRNA expression levels, the differential expression of G protein appears to be largely determined by posttranslational mechanisms that affect G protein stability. Pulse-chase experiments indicated that the G protein of CVS-B2c is degraded more slowly than that of CVS-N2c. The accumulation of G protein correlated with the induction of programmed cell death in CVS-B2c-infected neurons. The extent of apoptosis was considerably lower in CVS-N2c-infected neurons, where G protein expression was minimal. While nucleoprotein (N protein) expression levels were similar in neurons infected with either variant, the transport of N protein into neuronal processes was strongly inhibited in CVS-B2c-infected cells. Thus, downregulation of G protein expression in neuronal cells evidently contributes to rabies virus pathogenesis by preventing apoptosis and the apparently associated failure of the axonal transport of N protein.

  13. Experimental co-infections of domestic ducks with a virulent Newcastle disease virus and low or highly pathogenic avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infections with Avian influenza viruses (AIV) of low and high pathogenicity (LP and HP), and Newcastle disease virus (NDV) are commonly reported in domestic ducks in parts of the world. However, it’s not clear if co-infections with these viruses affect the severity of the diseases they produce, the ...

  14. [Serologic studies of domestic cats for potential human pathogenic virus infections from wild rodents].

    PubMed

    Nowotny, N

    1996-05-01

    For several viral infections a reservoir in wild rodents has been demonstrated. Some of the agents are known or suspected to be pathogenic for humans. Because improvements in hygiene have reduced direct human contact with rodents, domestic cats could be acting as active transmitters of these viruses from rodents to man. We selected 4 such pathogens--ortho- and parapox-, hanta- and encephalomyocarditis viruses--which, in different ways, may lead to serious human illness: Ortho- and parapoxvirus infections may cause localized pox lesions following direct skin contact. In general, the lesions heal without complications; in immunosuppressed or -deficient individuals, however, infection may generalize and take a dramatic course. Hantaviruses exist in various serotypes with different pathogenicity for human beings, varying from asymptomatic infection to highly fatal disease. In central and northern Europe the Puumala serotype is predominant causing influenza-like symptoms and renal dysfunction. Human infections arise from inhalation of aerosolized excreta of persistently infected rodents. Infections of man associated with encephalomyocarditis virus were demonstrated sporadically in cases of encephalitis and meningitis. In the present study, we investigated in 200 feline serum samples the prevalence of antibodies to ortho- and parapox-, hanta- and encephalomyocarditis virus. All serum samples were from cats that had been allowed to roam outside and to hunt. They were submitted from all parts of Austria for routine diagnosis in 1993. Four per cent of cats showed antibodies to orthopoxviruses with haemagglutination inhibition (HI) titres of 16-512; because of extensive cross-reactivity, positive samples reacted with all investigated orthopoxviruses (a feline orthopoxvirus recently isolated in Vienna, the reference strain of cowpox virus, Brighton, and vaccinia virus, strain IHD), only varying in titre. The specificity of the results was confirmed by virus neutralisation (VN

  15. Expression of a Peroral Infection Factor Determines Pathogenicity and Population Structure in an Insect Virus

    PubMed Central

    Simón, Oihane; Williams, Trevor; Cerutti, Martine; Caballero, Primitivo; López-Ferber, Miguel

    2013-01-01

    A Nicaraguan isolate of Spodoptera frugiperda multiple nucleopolyhedrovirus is being studied as a possible biological insecticide. This virus exists as a mixture of complete and deletion genotypes; the latter depend on the former for the production of an essential per os transmission factor (pif1) in coinfected cells. We hypothesized that the virus population was structured to account for the prevalence of pif1 defector genotypes, so that increasing the abundance of pif1 produced by a cooperator genotype in infected cells would favor an increased prevalence of the defector genotype. We tested this hypothesis using recombinant viruses with pif1 expression reprogrammed at its native locus using two exogenous promoters (egt, p10) in the pif2/pif1 intergenic region. Reprogrammed viruses killed their hosts markedly faster than the wild-type and rescue viruses, possibly due to an earlier onset of systemic infection. Group success (transmission) depended on expression of pif1, but overexpression was prejudicial to group-specific transmissibility, both in terms of reduced pathogenicity and reduced production of virus progeny from each infected insect. The presence of pif1-overproducing genotypes in the population was predicted to favor a shift in the prevalence of defector genotypes lacking pif1-expressing capabilities, to compensate for the modification in pif1 availability at the population level. As a result, defectors increased the overall pathogenicity of the virus population by diluting pif1 produced by overexpressing genotypes. These results offer a new and unexpected perspective on cooperative behavior between viral genomes in response to the abundance of an essential public good that is detrimental in excess. PMID:24223853

  16. Viruses accumulate in aging infection centers of a fungal forest pathogen

    PubMed Central

    Vainio, Eeva J; Müller, Michael M; Korhonen, Kari; Piri, Tuula; Hantula, Jarkko

    2015-01-01

    Fungal viruses (mycoviruses) with RNA genomes are believed to lack extracellular infective particles. These viruses are transmitted laterally among fungal strains through mycelial anastomoses or vertically via their infected spores, but little is known regarding their prevalence and patterns of dispersal under natural conditions. Here, we examined, in detail, the spatial and temporal changes in a mycovirus community and its host fungus Heterobasidion parviporum, the most devastating fungal pathogen of conifers in the Boreal forest region. During the 7-year sampling period, viruses accumulated in clonal host individuals as a result of indigenous viruses spreading within and between clones as well as novel strains arriving via airborne spores. Viral community changes produced pockets of heterogeneity within large H. parviporum clones. The appearance of novel viral infections in aging clones indicated that transient cell-to-cell contacts between Heterobasidion strains are likely to occur more frequently than what was inferred from genotypic analyses. Intraspecific variation was low among the three partitivirus species at the study site, whereas the unassigned viral species HetRV6 was highly polymorphic. The accumulation of point mutations during persistent infections resulted in viral diversification, that is, the presence of nearly identical viral sequence variants within single clones. Our results also suggest that co-infections by distantly related viral species are more stable than those between conspecific strains, and mutual exclusion may play a role in determining mycoviral communities. PMID:25126757

  17. Host immune responses of ducks infected with H5N1 highly pathogenic avian influenza viruses of different pathogenicities.

    PubMed

    Wei, Liangmeng; Jiao, Peirong; Song, Yafen; Cao, Lan; Yuan, Runyu; Gong, Lang; Cui, Jin; Zhang, Shuo; Qi, Wenbao; Yang, Su; Liao, Ming

    2013-10-25

    Our previous studies have illustrated three strains of duck-origin H5N1 highly pathogenic avian influenza viruses (HPAIVs) had varying levels of pathogenicity in ducks (Sun et al., 2011). However, the host immune response of ducks infected with those of H5N1 HPAIVs was unclear. Here, we compared viral distribution and mRNA expression of immune-related genes in ducks following infection with the two HPAIV (A/Duck/Guangdong/212/2004, DK212 and A/Duck/Guangdong/383/2008, DK383). DK383 could replicate in the tested tissue of ducks (brain, spleen, lungs, cloacal bursa, kidney, and pancreas) more rapid and efficiently than DK212 at 1 and 2 days post-inoculation. Quantitative real-time PCR analysis showed that the expression levels of TLR3, IL-6, IL-8, and MHC class II in brains were higher than those of respective genes in lungs during the early stage of post infection. Furthermore, the expression levels of IL-6 and IL-8 in the brain of ducks following infection with DK383 were remarkably higher than those of ducks infected with DK212, respectively. Our results suggest that the shift in the H5N1 HPAIVs to increased virulence in ducks may be associated with efficient and rapid replication of the virus, accompanied by early destruction of host immune responses. These data are helpful to understand the underlying mechanism of the different outcome of H5N1 HPAIVs infection in ducks.

  18. Recent insights into host-pathogen interaction in white spot syndrome virus infected penaeid shrimp.

    PubMed

    Shekhar, M S; Ponniah, A G

    2015-07-01

    Viral disease outbreaks are a major concern impeding the development of the shrimp aquaculture industry. The viral disease due to white spot syndrome virus (WSSV) observed in early 1990s still continues unabated affecting the shrimp farms and cause huge economic loss to the shrimp aquaculture industry. In the absence of effective therapeutics to control WSSV, it is important to understand viral pathogenesis and shrimp response to WSSV at the molecular level. Identification and molecular characterization of WSSV proteins and receptors may facilitate in designing and development of novel therapeutics and antiviral drugs that may inhibit viral replication. Investigations into host-pathogen interactions might give new insights to viral infectivity, tissue tropism and defence mechanism elicited in response to WSSV infection. However, due to the limited information on WSSV gene function and host immune response, the signalling pathways which are associated in shrimp pathogen interaction have also not been elucidated completely. In the present review, the focus is on those shrimp proteins and receptors that are potentially involved in virus infection or in the defence mechanism against WSSV. In addition, the major signalling pathways involved in the innate immune response and the role of apoptosis in host-pathogen interaction is discussed.

  19. Cytokine response in mouse bone marrow derived macrophages after infection with pathogenic and non-pathogenic Rift Valley fever virus

    PubMed Central

    Roberts, Kimberly K.; Hill, Terence E.; Davis, Melissa N.; Holbrook, Michael R.

    2015-01-01

    Rift Valley fever virus (RVFV) is the most pathogenic member of the genus Phlebovirus within the family Bunyaviridae, and can cause severe disease in humans and livestock. Until recently, limited information has been published on the cellular host response elicited by RVFV, particularly in macrophages and dendritic cells, which play critical roles in stimulating adaptive and innate immune responses to viral infection. In an effort to define the initial response of host immunomodulatory cells to infection, primary mouse bone marrow derived macrophages (BMDM) were infected with the pathogenic RVFV strain ZH501, or attenuated strains MP-12 or MP-12 based Clone13 type (rMP12-C13 type), and cytokine secretion profiles examined. The secretion of T helper (Th)1-associated antiviral cytokines, chemokines and various interleukins increased rapidly after infection with the attenuated rMP12-C13 type RVFV, which lacks a functional NSs virulence gene. In comparison, infection with live-attenuated MP-12 encoding a functional NSs gene appeared to cause a delayed immune response, while pathogenic ZH501 ablates the immune response almost entirely. These data demonstrate that NSs can inhibit components of the BMDM antiviral response and supports previous work indicating that NSs can specifically regulate the type I interferon response in macrophages. Furthermore, our data demonstrate that genetic differences between ZH501 and MP-12 reduce the ability of MP-12 to inhibit antiviral signalling and subsequently reduce virulence in BMDM, demonstrating that viral components other than NSs play a critical role in regulating the host response to RVFV infection. PMID:25759029

  20. Plasmacytoid Dendritic Cell Infection and Sensing Capacity during Pathogenic and Nonpathogenic Simian Immunodeficiency Virus Infection

    PubMed Central

    Jochems, Simon P.; Jacquelin, Beatrice; Chauveau, Lise; Huot, Nicolas; Petitjean, Gaël; Lepelley, Alice; Liovat, Anne-Sophie; Ploquin, Mickaël J.; Cartwright, Emily K.; Bosinger, Steven E.; Silvestri, Guido; Barré-Sinoussi, Françoise; Lebon, Pierre; Schwartz, Olivier

    2015-01-01

    ABSTRACT Human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques (MAC) lead to chronic inflammation and AIDS. Natural hosts, such as African green monkeys (AGM) and sooty mangabeys (SM), are protected against SIV-induced chronic inflammation and AIDS. Here, we report that AGM plasmacytoid dendritic cells (pDC) express extremely low levels of CD4, unlike MAC and human pDC. Despite this, AGM pDC efficiently sensed SIVagm, but not heterologous HIV/SIV isolates, indicating a virus-host adaptation. Moreover, both AGM and SM pDC were found to be, in contrast to MAC pDC, predominantly negative for CCR5. Despite such limited CD4 and CCR5 expression, lymphoid tissue pDC were infected to a degree similar to that seen with CD4+ T cells in both MAC and AGM. Altogether, our finding of efficient pDC infection by SIV in vivo identifies pDC as a potential viral reservoir in lymphoid tissues. We discovered low expression of CD4 on AGM pDC, which did not preclude efficient sensing of host-adapted viruses. Therefore, pDC infection and efficient sensing are not prerequisites for chronic inflammation. The high level of pDC infection by SIVagm suggests that if CCR5 paucity on immune cells is important for nonpathogenesis of natural hosts, it is possibly not due to its role as a coreceptor. IMPORTANCE The ability of certain key immune cell subsets to resist infection might contribute to the asymptomatic nature of simian immunodeficiency virus (SIV) infection in its natural hosts, such as African green monkeys (AGM) and sooty mangabeys (SM). This relative resistance to infection has been correlated with reduced expression of CD4 and/or CCR5. We show that plasmacytoid dendritic cells (pDC) of natural hosts display reduced CD4 and/or CCR5 expression, unlike macaque pDC. Surprisingly, this did not protect AGM pDC, as infection levels were similar to those found in MAC pDC. Furthermore, we show that AGM pDC did not consistently produce type I

  1. Virus interference between H7N2 low pathogenic avian influenza virus and lentogenic Newcastle disease virus in experimental co-infections in chickens and turkeys

    PubMed Central

    2014-01-01

    Low pathogenicity avian influenza virus (LPAIV) and lentogenic Newcastle disease virus (lNDV) are commonly reported causes of respiratory disease in poultry worldwide with similar clinical and pathobiological presentation. Co-infections do occur but are not easily detected, and the impact of co-infections on pathobiology is unknown. In this study chickens and turkeys were infected with a lNDV vaccine strain (LaSota) and a H7N2 LPAIV (A/turkey/VA/SEP-67/2002) simultaneously or sequentially three days apart. No clinical signs were observed in chickens co-infected with the lNDV and LPAIV or in chickens infected with the viruses individually. However, the pattern of virus shed was different with co-infected chickens, which excreted lower titers of lNDV and LPAIV at 2 and 3 days post inoculation (dpi) and higher titers at subsequent time points. All turkeys inoculated with the LPAIV, whether or not they were exposed to lNDV, presented mild clinical signs. Co-infection effects were more pronounced in turkeys than in chickens with reduction in the number of birds shedding virus and in virus titers, especially when LPAIV was followed by lNDV. In conclusion, co-infection of chickens or turkeys with lNDV and LPAIV affected the replication dynamics of these viruses but did not affect clinical signs. The effect on virus replication was different depending on the species and on the time of infection. These results suggest that infection with a heterologous virus may result in temporary competition for cell receptors or competent cells for replication, most likely interferon-mediated, which decreases with time. PMID:24393488

  2. Sequence of Pathogenic Events in Cynomolgus Macaques Infected with Aerosolized Monkeypox Virus

    PubMed Central

    Hall, G.; Pearson, G.; Rayner, E.; Graham, V. A.; Steeds, K.; Bewley, K. R.; Hatch, G. J.; Dennis, M.; Taylor, I.; Roberts, A. D.; Funnell, S. G. P.; Vipond, J.

    2015-01-01

    ABSTRACT To evaluate new vaccines when human efficacy studies are not possible, the FDA's “Animal Rule” requires well-characterized models of infection. Thus, in the present study, the early pathogenic events of monkeypox infection in nonhuman primates, a surrogate for variola virus infection, were characterized. Cynomolgus macaques were exposed to aerosolized monkeypox virus (105 PFU). Clinical observations, viral loads, immune responses, and pathological changes were examined on days 2, 4, 6, 8, 10, and 12 postchallenge. Viral DNA (vDNA) was detected in the lungs on day 2 postchallenge, and viral antigen was detected, by immunostaining, in the epithelium of bronchi, bronchioles, and alveolar walls. Lesions comprised rare foci of dysplastic and sloughed cells in respiratory bronchioles. By day 4, vDNA was detected in the throat, tonsil, and spleen, and monkeypox antigen was detected in the lung, hilar and submandibular lymph nodes, spleen, and colon. Lung lesions comprised focal epithelial necrosis and inflammation. Body temperature peaked on day 6, pox lesions appeared on the skin, and lesions, with positive immunostaining, were present in the lung, tonsil, spleen, lymph nodes, and colon. By day 8, vDNA was present in 9/13 tissues. Blood concentrations of interleukin 1ra (IL-1ra), IL-6, and gamma interferon (IFN-γ) increased markedly. By day 10, circulating IgG antibody concentrations increased, and on day 12, animals showed early signs of recovery. These results define early events occurring in an inhalational macaque monkeypox infection model, supporting its use as a surrogate model for human smallpox. IMPORTANCE Bioterrorism poses a major threat to public health, as the deliberate release of infectious agents, such smallpox or a related virus, monkeypox, would have catastrophic consequences. The development and testing of new medical countermeasures, e.g., vaccines, are thus priorities; however, tests for efficacy in humans cannot be performed because it

  3. The Nonstructural Proteins of Nipah Virus Play a Key Role in Pathogenicity in Experimentally Infected Animals

    PubMed Central

    Yoneda, Misako; Guillaume, Vanessa; Sato, Hiroki; Fujita, Kentaro; Georges-Courbot, Marie-Claude; Ikeda, Fusako; Omi, Mio; Muto-Terao, Yuri; Wild, T. Fabian; Kai, Chieko

    2010-01-01

    Nipah virus (NiV) P gene encodes P protein and three accessory proteins (V, C and W). It has been reported that all four P gene products have IFN antagonist activity when the proteins were transiently expressed. However, the role of those accessory proteins in natural infection with NiV remains unknown. We generated recombinant NiVs lacking V, C or W protein, rNiV(V−), rNiV(C−), and rNiV(W−), respectively, to analyze the functions of these proteins in infected cells and the implications in in vivo pathogenicity. All the recombinants grew well in cell culture, although the maximum titers of rNiV(V−) and rNiV(C−) were lower than the other recombinants. The rNiV(V−), rNiV(C−) and rNiV(W−) suppressed the IFN response as well as the parental rNiV, thereby indicating that the lack of each accessory protein does not significantly affect the inhibition of IFN signaling in infected cells. In experimentally infected golden hamsters, rNiV(V−) and rNiV(C−) but not the rNiV(W−) virus showed a significant reduction in virulence. These results suggest that V and C proteins play key roles in NiV pathogenicity, and the roles are independent of their IFN-antagonist activity. This is the first report that identifies the molecular determinants of NiV in pathogenicity in vivo. PMID:20856799

  4. Pathogenicity of Highly Pathogenic Avian Influenza Virus H5N1 in Naturally Infected Poultry in Egypt.

    PubMed

    Hagag, Ibrahim Thabet; Mansour, Shimaa M G; Zhang, Zerui; Ali, Ahmed A H; Ismaiel, El-Bakry M; Salama, Ali A; Cardona, Carol J; Collins, James; Xing, Zheng

    2015-01-01

    Highly pathogenic avian influenza virus (HPAIV) H5N1 has been endemic in Egypt since 2006, and there is increasing concern for its potential to become highly transmissible among humans. Infection by HPAIV H5N1 has been described in experimentally challenged birds. However, the pathogenicity of the H5N1 isolated in Egypt has never been reported in naturally infected chickens and ducks. Here we report a 2013 outbreak of HPAIV H5N1 in commercial poultry farms and backyards in Sharkia Province, Egypt. The main symptoms were ecchymosis on the shanks and feet, cyanosis of the comb and wattles, subcutaneous edema of the head and neck for chickens, and nervous signs (torticollis) for ducks. Within 48-72 hrs of the onset of illness, the average mortality rates were 22.8-30% and 28.5-40% in vaccinated chickens and non-vaccinated ducks, respectively. Tissue samples of chickens and ducks were collected for analyses with cross-section immunohistochemistry and real-time RT-PCR for specific viral RNA transcripts. While viral RNA was detected in nearly all tissues and sera collected, viral nucleoprotein was detected almost ubiquitously in all tissues, including testis. Interestingly, viral antigen was also observed in endothelial cells of most organs in chickens, and clearly detected in the trachea and brain in particular. Viral nucleoprotein was also detected in mononuclear cells of various organs, especially pulmonary tissue. We performed phylogenetic analyses and compared the genomic sequences of the hemagglutinin (HA) and nonstructural proteins (NS) among the isolated viruses, the HPAIV circulated in Egypt in the past and currently, and some available vaccine strains. Further analysis of deduced amino acids of both HA and NS1 revealed that our isolates carried molecular determinants of HPAIV, including the multibasic amino acids (PQGERRRK/KR*GLF) in the cleavage site in HA and glutamate at position 92 (D92E) in NS1. This is the first report of the pathogenicity of the HPAIVH5N

  5. Pathogenicity of Highly Pathogenic Avian Influenza Virus H5N1 in Naturally Infected Poultry in Egypt

    PubMed Central

    Hagag, Ibrahim Thabet; Mansour, Shimaa M. G.; Zhang, Zerui; Ali, Ahmed A. H.; Ismaiel, El-Bakry M.; Salama, Ali A.; Cardona, Carol J.; Collins, James; Xing, Zheng

    2015-01-01

    Highly pathogenic avian influenza virus (HPAIV) H5N1 has been endemic in Egypt since 2006, and there is increasing concern for its potential to become highly transmissible among humans. Infection by HPAIV H5N1 has been described in experimentally challenged birds. However, the pathogenicity of the H5N1 isolated in Egypt has never been reported in naturally infected chickens and ducks. Here we report a 2013 outbreak of HPAIV H5N1 in commercial poultry farms and backyards in Sharkia Province, Egypt. The main symptoms were ecchymosis on the shanks and feet, cyanosis of the comb and wattles, subcutaneous edema of the head and neck for chickens, and nervous signs (torticollis) for ducks. Within 48-72 hrs of the onset of illness, the average mortality rates were 22.8-30% and 28.5-40% in vaccinated chickens and non-vaccinated ducks, respectively. Tissue samples of chickens and ducks were collected for analyses with cross-section immunohistochemistry and real-time RT-PCR for specific viral RNA transcripts. While viral RNA was detected in nearly all tissues and sera collected, viral nucleoprotein was detected almost ubiquitously in all tissues, including testis. Interestingly, viral antigen was also observed in endothelial cells of most organs in chickens, and clearly detected in the trachea and brain in particular. Viral nucleoprotein was also detected in mononuclear cells of various organs, especially pulmonary tissue. We performed phylogenetic analyses and compared the genomic sequences of the hemagglutinin (HA) and nonstructural proteins (NS) among the isolated viruses, the HPAIV circulated in Egypt in the past and currently, and some available vaccine strains. Further analysis of deduced amino acids of both HA and NS1 revealed that our isolates carried molecular determinants of HPAIV, including the multibasic amino acids (PQGERRRK/KR*GLF) in the cleavage site in HA and glutamate at position 92 (D92E) in NS1. This is the first report of the pathogenicity of the HPAIVH5N

  6. High Pathogenicity of Wild-Type Measles Virus Infection in CD150 (SLAM) Transgenic Mice

    PubMed Central

    Sellin, Caroline I.; Davoust, Nathalie; Guillaume, Vanessa; Baas, Dominique; Belin, Marie-Françoise; Buckland, Robin; Wild, T. Fabian; Horvat, Branka

    2006-01-01

    Measles virus (MV) infection causes an acute childhood disease, associated in certain cases with infection of the central nervous system and development of a severe neurological disease. We have generated transgenic mice ubiquitously expressing the human protein SLAM (signaling lymphocytic activation molecule), or CD150, recently identified as an MV receptor. In contrast to all other MV receptor transgenic models described so far, in these mice infection with wild-type MV strains is highly pathogenic. Intranasal infection of SLAM transgenic suckling mice leads to MV spread to different organs and the development of an acute neurological syndrome, characterized by lethargy, seizures, ataxia, weight loss, and death within 3 weeks. In addition, in this model, vaccine and wild-type MV strains can be distinguished by virulence. Furthermore, intracranial MV infection of adult transgenic mice generates a subclinical infection associated with a high titer of MV-specific antibodies in the serum. Finally, to analyze new antimeasles therapeutic approaches, we created a recombinant soluble form of SLAM and demonstrated its important antiviral activity both in vitro and in vivo. Taken together, our results show the high susceptibility of SLAM transgenic mice to MV-induced neurological disease and open new perspectives for the analysis of the implication of SLAM in the neuropathogenicity of other morbilliviruses, which also use this molecule as a receptor. Moreover, this transgenic model, in allowing a simple readout of the efficacy of an antiviral treatment, provides unique experimental means to test novel anti-MV preventive and therapeutic strategies. PMID:16775330

  7. Three-Dimensional Structure of a Protozoal Double-Stranded RNA Virus That Infects the Enteric Pathogen Giardia lamblia

    PubMed Central

    Janssen, Mandy E. W.; Takagi, Yuko; Parent, Kristin N.; Cardone, Giovanni

    2014-01-01

    ABSTRACT Giardia lamblia virus (GLV) is a small, nonenveloped, nonsegmented double-stranded RNA (dsRNA) virus infecting Giardia lamblia, the most common protozoan pathogen of the human intestine and a major agent of waterborne diarrheal disease worldwide. GLV (genus Giardiavirus) is a member of family Totiviridae, along with several other groups of protozoal or fungal viruses, including Leishmania RNA viruses and Trichomonas vaginalis viruses. Interestingly, GLV is more closely related than other Totiviridae members to a group of recently discovered metazoan viruses that includes penaeid shrimp infectious myonecrosis virus (IMNV). Moreover, GLV is the only known protozoal dsRNA virus that can transmit efficiently by extracellular means, also like IMNV. In this study, we used transmission electron cryomicroscopy and icosahedral image reconstruction to examine the GLV virion at an estimated resolution of 6.0 Å. Its outermost diameter is 485 Å, making it the largest totivirus capsid analyzed to date. Structural comparisons of GLV and other totiviruses highlighted a related “T=2” capsid organization and a conserved helix-rich fold in the capsid subunits. In agreement with its unique capacity as a protozoal dsRNA virus to survive and transmit through extracellular environments, GLV was found to be more thermoresistant than Trichomonas vaginalis virus 1, but no specific protein machinery to mediate cell entry, such as the fiber complexes in IMNV, could be localized. These and other structural and biochemical findings provide a basis for future work to dissect the cell entry mechanism of GLV into a “primitive” (early-branching) eukaryotic host and an important enteric pathogen of humans. IMPORTANCE Numerous pathogenic bacteria, including Corynebacterium diphtheriae, Salmonella enterica, and Vibrio cholerae, are infected with lysogenic bacteriophages that contribute significantly to bacterial virulence. In line with this phenomenon, several pathogenic protozoa

  8. Pathology of highly pathogenic avian influenza virus (H5N1) infection in Canada geese (Branta canadensis): preliminary studies.

    PubMed

    Neufeld, J L; Embury-Hyatt, C; Berhane, Y; Manning, L; Ganske, S; Pasick, J

    2009-09-01

    Susceptibility of Canada geese (Branta canadensis) to highly pathogenic avian influenza (HPAI) virus (H5N1) infection was studied by inoculating 10 naïve (antibody-negative) animals (5 adults and 5 juveniles) with A/chicken/Vietnam/14/05 (H5N1) virus. In the adults, 1 of 5 became infected, and 4 of 5 remained normal; in the juvenile group, 5 of 5 became infected. The pathology observed in the affected animals was similar to that reported in natural occurrences. Peripheral and parasympathetic nervous systems were examined and found infected, as well as cerebrospinal fluid-contacting neurons. In some locations with significant virus infection in cells, the expected inflammatory reaction was absent or very mild. Immunohistochemistry was used to locate influenza A virus nucleoprotein in brain, spinal cord, respiratory and digestive systems, pancreas, heart, and peripheral and parasympathetic nervous systems. Further studies are needed to explain age-related differences in susceptibility.

  9. Susceptibility And Adaptation Of A Mallard H5N2 Low Pathogenic Influenza Virus In Chickens Infected With Infectious Bursal Disease Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The influenza A/Mallard/Pennsylvania/12180/1984 (H5N2) virus is unable to replicate in 2 to 4-week old normal, immunocompetent specific-pathogen-free (SPF) chickens. In contrast, this mallard virus shows limited replication in chickens that had been previously infected with the immunosuppressive age...

  10. Evidence of infection by H5N2 highly pathogenic avian influenza viruses in healthy wild waterfowl

    USGS Publications Warehouse

    Gaidet, N.; Cattoli, G.; Hammoumi, S.; Newman, S.H.; Hagemeijer, W.; Takekawa, J.Y.; Cappelle, J.; Dodman, T.; Joannis, T.; Gil, P.; Monne, I.; Fusaro, A.; Capua, I.; Manu, S.; Micheloni, P.; Ottosson, U.; Mshelbwala, J.H.; Lubroth, J.; Domenech, J.; Monicat, F.

    2008-01-01

    The potential existence of a wild bird reservoir for highly pathogenic avian influenza (HPAI) has been recently questioned by the spread and the persisting circulation of H5N1 HPAI viruses, responsible for concurrent outbreaks in migratory and domestic birds over Asia, Europe, and Africa. During a large-scale surveillance programme over Eastern Europe, the Middle East, and Africa, we detected avian influenza viruses of H5N2 subtype with a highly pathogenic (HP) viral genotype in healthy birds of two wild waterfowl species sampled in Nigeria. We monitored the survival and regional movements of one of the infected birds through satellite telemetry, providing a rare evidence of a non-lethal natural infection by an HP viral genotype in wild birds. Phylogenetic analysis of the H5N2 viruses revealed close genetic relationships with H5 viruses of low pathogenicity circulating in Eurasian wild and domestic ducks. In addition, genetic analysis did not reveal known gallinaceous poultry adaptive mutations, suggesting that the emergence of HP strains could have taken place in either wild or domestic ducks or in non-gallinaceous species. The presence of coexisting but genetically distinguishable avian influenza viruses with an HP viral genotype in two cohabiting species of wild waterfowl, with evidence of non-lethal infection at least in one species and without evidence of prior extensive circulation of the virus in domestic poultry, suggest that some strains with a potential high pathogenicity for poultry could be maintained in a community of wild waterfowl.

  11. Experimental co-infections of domestic ducks with a virulent Newcastle disease virus and low or highly pathogenic avian influenza viruses

    PubMed Central

    Pantin-Jackwood, Mary; Costa-Hurtado, Mar; Miller, Patti J.; Afonso, Claudio L.; Spackman, Erica; Kapczynski, Darrell; Shepherd, Eric; Smith, Diane; Swayne, David

    2015-01-01

    Infections with avian influenza viruses (AIV) of low and high pathogenicity (LP and HP) and Newcastle disease virus (NDV) are commonly reported in domestic ducks in many parts of the world. However, it’s not clear if co-infections with these viruses affect the severity of the diseases they produce, the amount of virus shed, and transmission of the viruses. In this study we infected domestic ducks with a virulent NDV virus (vNDV) and either a LPAIV or a HPAIV by giving the viruses individually, simultaneously, or sequentially two days apart. No clinical signs were observed in ducks infected or co-infected with vNDV and LPAIV, but co-infection decreased the number of ducks shedding vNDV and the amount of virus shed (P <0.01) at 4 days post inoculation (dpi). Co-infection didn’t affect the number of birds shedding LPAIV, but more LPAIV was shed at 2 dpi (P <0.0001) from ducks inoculated with only LPAIV compared to ducks co-infected with vNDV. Ducks that received the HPAIV with the vNDV simultaneously survived fewer days (P <0.05) compared to the ducks that received the vNDV two days before the HPAIV. Co-infection also reduced transmission of vNDV to naïve contact ducks housed with the inoculated ducks. In conclusion, domestic ducks can become co-infected with vNDV and LPAIV with no effect on clinical signs but with reduction of virus shedding and transmission. These findings indicate that infection with one virus can interfere with replication of another, modifying the pathogenesis and transmission of the viruses. PMID:25759292

  12. Experimental co-infections of domestic ducks with a virulent Newcastle disease virus and low or highly pathogenic avian influenza viruses.

    PubMed

    Pantin-Jackwood, Mary J; Costa-Hurtado, Mar; Miller, Patti J; Afonso, Claudio L; Spackman, Erica; Kapczynski, Darrell R; Shepherd, Eric; Smith, Diane; Swayne, David E

    2015-05-15

    Infections with avian influenza viruses (AIV) of low and high pathogenicity (LP and HP) and Newcastle disease virus (NDV) are commonly reported in domestic ducks in many parts of the world. However, it is not clear if co-infections with these viruses affect the severity of the diseases they produce, the amount of virus shed, and transmission of the viruses. In this study we infected domestic ducks with a virulent NDV virus (vNDV) and either a LPAIV or a HPAIV by giving the viruses individually, simultaneously, or sequentially two days apart. No clinical signs were observed in ducks infected or co-infected with vNDV and LPAIV, but co-infection decreased the number of ducks shedding vNDV and the amount of virus shed (P<0.01) at 4 days post inoculation (dpi). Co-infection did not affect the number of birds shedding LPAIV, but more LPAIV was shed at 2 dpi (P<0.0001) from ducks inoculated with only LPAIV compared to ducks co-infected with vNDV. Ducks that received the HPAIV with the vNDV simultaneously survived fewer days (P<0.05) compared to the ducks that received the vNDV two days before the HPAIV. Co-infection also reduced transmission of vNDV to naïve contact ducks housed with the inoculated ducks. In conclusion, domestic ducks can become co-infected with vNDV and LPAIV with no effect on clinical signs but with reduction of virus shedding and transmission. These findings indicate that infection with one virus can interfere with replication of another, modifying the pathogenesis and transmission of the viruses.

  13. Variability in pathobiology of South Korean H5N1 high-pathogenicity avian influenza virus infection for 5 species of migratory waterfowl

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The biological outcome of H5N1 high pathogenicity avian influenza (HPAI) virus infection in wild waterfowl is poorly understood. This study examined infectivity and pathobiology of A/chicken/Korea/IS/06 (H5N1) HPAI virus infection in Mute swans (Cygnus olor), Greylag geese (Anser anser), Ruddy Sheld...

  14. Experimental infection of SPF and Korean native chickens with highly pathogenic avian influenza virus (H5N8).

    PubMed

    Lee, Eun-Kyoung; Song, Byung-Min; Kang, Hyun-Mi; Woo, Sang-Hee; Heo, Gyeong-Beom; Jung, Suk Chan; Park, Yong Ho; Lee, Youn-Jeong; Kim, Jae-Hong

    2016-05-01

    In 2014, an H5N8 outbreak of highly pathogenic avian influenza (HPAI) occurred in South Korea. The H5N8 strain produced mild to moderate clinical signs and mortality rates in commercial chicken farms, especially Korean native chicken farms. To understand the differences between their pathogenicity in SPF chicken and Korean native chicken., we evaluated the mean bird lethal doses (BLD50) of the Korean representative H5N8 virus (A/broiler duck/Korea/Buan2/2014) The BLD50values of the H5N8 virus were 10(5.3)EID50 and 10(6.7)EID50 in SPF and Korean native chickens, respectively. In addition, the mean death time was much longer, and the viral titers in tissues of H5N8-infected chickens were significantly lower, in the Korean group than in the SPF group. These features of the H5N8 virus likely account for its mild-to-moderate pathogenicity in commercial chicken farms, especially Korean native chicken flocks, despite the fact that it is a highly pathogenic virus according to the OIE criteria. To improve current understanding and management of HPAI, pathogenic characterization of novel emerging viruses should be performed by natural route in major poultry species in each country.

  15. First reported detection of a low pathogenicity avian influenza virus subtype H9 infection in domestic fowl in England.

    PubMed

    Parker, C D; Reid, S M; Ball, A; Cox, W J; Essen, S C; Hanna, A; Mahmood, S; Slomka, M J; Irvine, R M; Brown, I H

    2012-10-13

    In December 2010, infection with a H9N1 low pathogenicity avian influenza (LPAI) virus was detected in a broiler breeder flock in East Anglia. Disease suspicion was based on acute drops in egg production in two of four sheds on the premises, poor egg shell quality and evidence of diarrhoea. H9N1 LPAI virus infection was confirmed by real-time reverse transcription PCR. Sequencing revealed high nucleotide identity of 93.6 per cent and 97.9 per cent with contemporary North American H9 and Eurasian N1 genes, respectively. Attempted virus isolation in embryonated specific pathogen free (SPF) fowls' eggs was unsuccessful. Epidemiological investigations were conducted to identify the source of infection and any onward spread. These concluded that infection was restricted to the affected premises, and no contacts or movements of poultry, people or fomites could be attributed as the source of infection. However, the infection followed a period of extremely cold weather and snow which impacted on the biosecurity protocols on site, and also led to increased wild bird activity locally, including waterfowl and game birds around the farm buildings. Analysis of the N1 gene sequence suggested direct introduction from wild birds. Although H9 infection in poultry is not notifiable, H9N2 LPAI viruses have been associated with production and mortality episodes in poultry in many parts of Asia and the Middle East. In the present H9N1 outbreak, clinical signs were relatively mild in the poultry with no mortality, transient impact on egg production and no indication of zoonotic spread. However, this first reported detection of H9 LPAI virus in chickens in England was also the first H9 UK poultry case for 40 years, and vindicates the need for continued vigilance and surveillance of avian influenza viruses in poultry populations. PMID:22949546

  16. Prevention of immunodeficiency virus induced CD4+ T-cell depletion by prior infection with a non-pathogenic virus

    SciTech Connect

    TerWee, Julie A.; Carlson, Jennifer K.; Sprague, Wendy S.; Sondgeroth, Kerry S.; Shropshire, Sarah B.; Troyer, Jennifer L.; VandeWoude, Sue

    2008-07-20

    Immune dysregulation initiated by a profound loss of CD4+ T-cells is fundamental to HIV-induced pathogenesis. Infection of domestic cats with a non-pathogenic lentivirus prevalent in the puma (puma lentivirus, PLV or FIV{sub PCO}) prevented peripheral blood CD4+ T-cell depletion caused by subsequent virulent FIV infection. Maintenance of this critical population was not associated with a significant decrease in FIV viremia, lending support to the hypothesis that direct viral cytopathic effect is not the primary cause of immunodeficiency. Although this approach was analogous to immunization with a modified live vaccine, correlates of immunity such as a serum-neutralizing antibody or virus-specific T-cell proliferative response were not found in protected animals. Differences in cytokine transcription profile, most notably in interferon gamma, were observed between the protected and unprotected groups. These data provide support for the importance of non-adaptive enhancement of the immune response in the prevention of CD4+ T-cell loss.

  17. Ostrich ( Struthio camelus ) Infected with H5N8 Highly Pathogenic Avian Influenza Virus in South Korea in 2014.

    PubMed

    Kim, Hye-Ryoung; Kwon, Yong-Kuk; Lee, Youn-Jeong; Kang, Hyun-Mi; Lee, Eun-Kyoung; Song, Byung-Min; Jung, Suk-Chan; Lee, Kyung-Hyun; Lee, Hyun-Kyoung; Baek, Kang-Hyun; Bae, You-Chan

    2016-06-01

    Highly pathogenic avian influenza (HPAI) virus of the H5N8 subtype was isolated from a young ostrich in South Korea in March 2014. Clinical signs characterized by anorexia, depression, and signs of nervousness were observed. The isolated A/ostrich/Korea/H829/2014 (H5N8) virus had a cleavage site motif containing multiple basic amino acids, typical of HPAI virus. The phylogenetic tree of the hemagglutinin gene of the H5 HPAI virus showed that this ostrich H5N8 virus belongs to clade 2.3.4.4 viruses together with H5N8 strains isolated from ducks and wild birds in South Korea in 2014. Pathologically, redness of pancreas, enlargement and hemorrhage of spleen, friability of brain, and hydropericardium were prominently found. Histologic legions were observed in pancreas, spleen, liver, lung, heart, and brain, and influenza A nucleoproteins were detected in the same organs by immunohistochemistry. Other ostriches farmed together in open camps were not infected with HPAI virus based on the serologic and virologic tests. The findings indicate that ostriches are susceptible to H5N8 HPAI virus, but this virus does not spread efficiently among ratites. PMID:27309301

  18. Loss of Anti-Viral Immunity by Infection with a Virus Encoding a Cross-Reactive Pathogenic Epitope

    PubMed Central

    Chen, Alex T.; Cornberg, Markus; Gras, Stephanie; Guillonneau, Carole; Rossjohn, Jamie; Trees, Andrew; Emonet, Sebastien; de la Torre, Juan C.; Welsh, Raymond M.; Selin, Liisa K.

    2012-01-01

    T cell cross-reactivity between different strains of the same virus, between different members of the same virus group, and even between unrelated viruses is a common occurrence. We questioned here how an intervening infection with a virus containing a sub-dominant cross-reactive T cell epitope would affect protective immunity to a previously encountered virus. Pichinde virus (PV) and lymphocytic choriomeningitis virus (LCMV) encode subdominant cross-reactive NP205–212 CD8 T cell epitopes sharing 6 of 8 amino acids, differing only in the MHC anchoring regions. These pMHC epitopes induce cross-reactive but non-identical T cell receptor (TCR) repertoires, and structural studies showed that the differing anchoring amino acids altered the conformation of the MHC landscape presented to the TCR. PV-immune mice receiving an intervening infection with wild type but not NP205-mutant LCMV developed severe immunopathology in the form of acute fatty necrosis on re-challenge with PV, and this pathology could be predicted by the ratio of NP205-specific to the normally immunodominant PV NP38–45 -specific T cells. Thus, cross-reactive epitopes can exert pathogenic properties that compromise protective immunity by impairing more protective T cell responses. PMID:22536152

  19. Rhesus macaques previously infected with simian/human immunodeficiency virus are protected from vaginal challenge with pathogenic SIVmac239.

    PubMed Central

    Miller, C J; McChesney, M B; Lü, X; Dailey, P J; Chutkowski, C; Lu, D; Brosio, P; Roberts, B; Lu, Y

    1997-01-01

    Nontraumatic vaginal inoculation of rhesus macaques with a simian/human immunodeficiency virus (SIV/HIV) chimera containing the envelope gene from HIV-1 89.6 (SHIV 89.6) results in systemic infection (Y. Lu, B. Brosio, M. Lafaile, J. Li, R. G. Collman, J. Sodroski, and C. J. Miller, J. Virol. 70:3045-3050, 1996). A total of five rhesus macaques have each been infected by exposure to at least three intravaginal inoculations of SHIV 89.6. The SHIV 89.6 infection is characterized by a transient viremia that evokes humoral and cellular immune responses to HIV and SIV antigens, but disease does not develop in animals infected with SHIV 89.6. To determine if a previous infection with SHIV 89.6 by vaginal inoculation could protect animals from vaginal challenge with pathogenic SIV, all five animals were intravaginally inoculated twice with pathogenic SIV-mac239. After challenge, all of the SHIV-immunized animals had low or undetectable viral RNA levels in plasma compared to control animals. Three of the five of the SHIV-immunized animals remained virus isolation negative for more than 8 months, while two became virus isolation positive. The presence of SIV Gag-specific cytotoxic T lymphocytes in peripheral blood mononuclear cells and SIV-specific antibodies in cervicovaginal secretions at the time of challenge was associated with resistance to pathogenic SIV infection after vaginal challenge. These results suggest that protection from sexual transmission of HIV may be possible by effectively stimulating both humoral and cellular antiviral immunity in the systemic and genital mucosal immune compartments. PMID:9032322

  20. Different routes of inoculation impact infectivity and pathogenesis of H5N1 high pathogenicity avian influenza virus infection in chickens and domestic ducks.

    PubMed

    Kwon, Y K; Swayne, D E

    2010-12-01

    The H5N1 type A influenza viruses classified as Qinghai-like virus (clade 2.2) are a unique lineage of type A influenza viruses with the capacity to produce significant disease and mortality in gallinaceous and anseriform birds, including domestic and wild ducks. The objective of this study was to determine the susceptibility and pathogenesis of chickens and domestic ducks to A/Whooper Swan/Mongolia/224/05 (H5N1) high pathogenicity avian influenza (HPAI) virus when administered through respiratory or alimentary routes of exposure. The chickens and ducks were more susceptible to the H5N1 HPAI virus, as evidenced by low infectious and lethal viral doses, when exposed by intranasal as compared to alimentary routes of inoculation (intragastric or oral-fed infected chicken meat). In the alimentary exposure pathogenesis study, pathologic changes included hemorrhage, necrosis, and inflammation in association with virus detection. These changes were generally observed in most of the visceral organs of chickens, between 2 and 4 days postinoculation (DPI), and are similar to lesions and virus localization seen in birds in natural cases or in experimental studies using the intranasal route. Alimentary exposure to the virus caused systemic infection in the ducks, characterized by moderate lymphocytic encephalitis, necrotized hepatitis, and pancreatitis with a corresponding demonstration of virus within the lesions. In both chickens and ducks with alimentary exposure, lesions, virus, or both were first demonstrated in the upper alimentary tract on 1 DPI, suggesting that the alimentary tract was the initial site affected upon consumption of infected meat or on gavage of virus in liquid medium. However, as demonstrated in the infectivity study in chickens, alimentary infection required higher exposure doses to produce infection as compared to intranasal exposure in chickens. These data suggest that upper respiratory exposure to H5N1 HPAI virus in birds is more likely to result in

  1. Experimental co-infection of SPF chickens with low pathogenicity avian influenza virus (LPAIV) subtypes H9N2, H5N2 and H7N9, and infectious bronchitis virus (IBV)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) and infectious bronchitis virus (IBV) are two of the most important respiratory viruses affecting poultry worldwide, but little is known about the effect of co-infection of these two viruses in poultry. Low pathogenicity (LP) AIV can produce from mild to moderate upper r...

  2. Highly (H5N1) and Low (H7N2) Pathogenic Avian Influenza Virus Infection in Falcons Via Nasochoanal Route and Ingestion of Experimentally Infected Prey

    PubMed Central

    Bertran, Kateri; Busquets, Núria; Abad, Francesc Xavier; García de la Fuente, Jorge; Solanes, David; Cordón, Iván; Costa, Taiana; Dolz, Roser; Majó, Natàlia

    2012-01-01

    An experimental infection with highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) viruses was carried out on falcons in order to examine the effects of these viruses in terms of pathogenesis, viral distribution in tissues and viral shedding. The distribution pattern of influenza virus receptors was also assessed. Captive-reared gyr-saker (Falco rusticolus x Falco cherrug) hybrid falcons were challenged with a HPAI H5N1 virus (A/Great crested grebe/Basque Country/06.03249/2006) or a LPAI H7N2 virus (A/Anas plathyrhynchos/Spain/1877/2009), both via the nasochoanal route and by ingestion of previously infected specific pathogen free chicks. Infected falcons exhibited similar infection dynamics despite the different routes of exposure, demonstrating the effectiveness of in vivo feeding route. H5N1 infected falcons died, or were euthanized, between 5–7 days post-infection (dpi) after showing acute severe neurological signs. Presence of viral antigen in several tissues was confirmed by immunohistochemistry and real time RT-PCR (RRT-PCR), which were generally associated with significant microscopical lesions, mostly in the brain. Neither clinical signs, nor histopathological findings were observed in any of the H7N2 LPAI infected falcons, although all of them had seroconverted by 11 dpi. Avian receptors were strongly present in the upper respiratory tract of the falcons, in accordance with the consistent oral viral shedding detected by RRT-PCR in both H5N1 HPAI and H7N2 LPAI infected falcons. The present study demonstrates that gyr-saker hybrid falcons are highly susceptible to H5N1 HPAI virus infection, as previously observed, and that they may play a major role in the spreading of both HPAI and LPAI viruses. For the first time in raptors, natural infection by feeding on infected prey was successfully reproduced. The use of avian prey species in falconry husbandry and wildlife rehabilitation facilities could put valuable birds of prey

  3. Highly (H5N1) and low (H7N2) pathogenic avian influenza virus infection in falcons via nasochoanal route and ingestion of experimentally infected prey.

    PubMed

    Bertran, Kateri; Busquets, Núria; Abad, Francesc Xavier; García de la Fuente, Jorge; Solanes, David; Cordón, Iván; Costa, Taiana; Dolz, Roser; Majó, Natàlia

    2012-01-01

    An experimental infection with highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) viruses was carried out on falcons in order to examine the effects of these viruses in terms of pathogenesis, viral distribution in tissues and viral shedding. The distribution pattern of influenza virus receptors was also assessed. Captive-reared gyr-saker (Falco rusticolus x Falco cherrug) hybrid falcons were challenged with a HPAI H5N1 virus (A/Great crested grebe/Basque Country/06.03249/2006) or a LPAI H7N2 virus (A/Anas plathyrhynchos/Spain/1877/2009), both via the nasochoanal route and by ingestion of previously infected specific pathogen free chicks. Infected falcons exhibited similar infection dynamics despite the different routes of exposure, demonstrating the effectiveness of in vivo feeding route. H5N1 infected falcons died, or were euthanized, between 5-7 days post-infection (dpi) after showing acute severe neurological signs. Presence of viral antigen in several tissues was confirmed by immunohistochemistry and real time RT-PCR (RRT-PCR), which were generally associated with significant microscopical lesions, mostly in the brain. Neither clinical signs, nor histopathological findings were observed in any of the H7N2 LPAI infected falcons, although all of them had seroconverted by 11 dpi. Avian receptors were strongly present in the upper respiratory tract of the falcons, in accordance with the consistent oral viral shedding detected by RRT-PCR in both H5N1 HPAI and H7N2 LPAI infected falcons. The present study demonstrates that gyr-saker hybrid falcons are highly susceptible to H5N1 HPAI virus infection, as previously observed, and that they may play a major role in the spreading of both HPAI and LPAI viruses. For the first time in raptors, natural infection by feeding on infected prey was successfully reproduced. The use of avian prey species in falconry husbandry and wildlife rehabilitation facilities could put valuable birds of prey and

  4. Corneal Opacity in Domestic Ducks Experimentally Infected With H5N1 Highly Pathogenic Avian Influenza Virus.

    PubMed

    Yamamoto, Y; Nakamura, K; Yamada, M; Mase, M

    2016-01-01

    Domestic ducks can be a key factor in the regional spread of H5N1 highly pathogenic avian influenza (HPAI) virus in Asia. The authors performed experimental infections to examine the relationship between corneal opacity and H5N1 HPAI virus infection in domestic ducks (Anas platyrhyncha var domestica). A total of 99 domestic ducks, including 3 control birds, were used in the study. In experiment 1, when domestic ducks were inoculated intranasally with 2 H5N1 HPAI viruses, corneal opacity appeared more frequently than neurologic signs and mortality. Corneal ulceration and exophthalmos were rare findings. Histopathologic examinations of the eyes of domestic ducks in experiment 2 revealed that corneal opacity was due to the loss of corneal endothelial cells and subsequent keratitis with edema. Influenza viral antigen was detected in corneal endothelial cells and some other ocular cells by immunohistochemistry. Results suggest that corneal opacity is a characteristic and frequent finding in domestic ducks infected with the H5N1 HPAI virus. Confirming this ocular change may improve the detection rate of infected domestic ducks in the field.

  5. Transmission of H5N1 high pathogenicity avian influenza virus to Herring gulls (Larus argentatus) through intranasal inoculation of virus and ingestion of virus-infected chicken meat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to evaluate the susceptibility of herring gulls (Larus argentatus) to H5N1 highly pathogenic avian influenza (HPAI) virus under natural routes of infection, we exposed gulls to two Asian lineage H5N1 HPAI viruses (A/whooper swan/Mongolia/244/05 and A/duck meat/Anyang/AVL-1/01) via intranasa...

  6. Host-pathogen dynamics of squirrelpox virus infection in red squirrels (Sciurus vulgaris).

    PubMed

    Fiegna, C; Dagleish, M P; Coulter, L; Milne, E; Meredith, A; Finlayson, J; Di Nardo, A; McInnes, C J

    2016-01-01

    To improve our understanding of squirrelpox virus (SQPV) infection in the susceptible host, three red squirrels were challenged with wild-type SQPV via scarification of the hind-limb skin. All squirrels seroconverted to the infection by the end of the experiment (17 days post-challenge). Challenged animals suffered disease characterised by the development of multiple skin and oral lesions with rapid progression of skin lesions at the infection site by day 10 post-challenge. No internal pathological changes were found at post-mortem examination. A novel SQPV Taqman(®) Real-time PCR detected viral DNA from multiple organs, with the largest amounts consistently associated with the primary and secondary skin and oral lesions where viral replication was most likely occurring. Immunohistochemistry clearly detected viral antigen in the stratified squamous epithelium of the epidermis, tongue and the oropharyngeal mucosa-associated lymphoid tissue and was consistently associated with histological changes resulting from viral replication. The lack of internal pathological changes and the detection of relatively low levels of viral DNA when compared with primary and secondary skin lesions argue against systemic disease, although systemic spread of the virus cannot be ruled out. This study allowed a comprehensive investigation of the clinical manifestation and progression of SQPV infection with a quantitative and qualitative analysis of virus dissemination and shedding. These findings suggest two separate routes of SQPV transmission under natural conditions, with both skin and saliva playing key roles in infected red squirrels.

  7. Host-pathogen dynamics of squirrelpox virus infection in red squirrels (Sciurus vulgaris).

    PubMed

    Fiegna, C; Dagleish, M P; Coulter, L; Milne, E; Meredith, A; Finlayson, J; Di Nardo, A; McInnes, C J

    2016-01-01

    To improve our understanding of squirrelpox virus (SQPV) infection in the susceptible host, three red squirrels were challenged with wild-type SQPV via scarification of the hind-limb skin. All squirrels seroconverted to the infection by the end of the experiment (17 days post-challenge). Challenged animals suffered disease characterised by the development of multiple skin and oral lesions with rapid progression of skin lesions at the infection site by day 10 post-challenge. No internal pathological changes were found at post-mortem examination. A novel SQPV Taqman(®) Real-time PCR detected viral DNA from multiple organs, with the largest amounts consistently associated with the primary and secondary skin and oral lesions where viral replication was most likely occurring. Immunohistochemistry clearly detected viral antigen in the stratified squamous epithelium of the epidermis, tongue and the oropharyngeal mucosa-associated lymphoid tissue and was consistently associated with histological changes resulting from viral replication. The lack of internal pathological changes and the detection of relatively low levels of viral DNA when compared with primary and secondary skin lesions argue against systemic disease, although systemic spread of the virus cannot be ruled out. This study allowed a comprehensive investigation of the clinical manifestation and progression of SQPV infection with a quantitative and qualitative analysis of virus dissemination and shedding. These findings suggest two separate routes of SQPV transmission under natural conditions, with both skin and saliva playing key roles in infected red squirrels. PMID:26711024

  8. Highly pathogenic avian influenza viruses do not inhibit interferon synthesis in infected chickens but can override the interferon-induced antiviral state.

    PubMed

    Penski, Nicola; Härtle, Sonja; Rubbenstroth, Dennis; Krohmann, Carsten; Ruggli, Nicolas; Schusser, Benjamin; Pfann, Michael; Reuter, Antje; Gohrbandt, Sandra; Hundt, Jana; Veits, Jutta; Breithaupt, Angele; Kochs, Georg; Stech, Jürgen; Summerfield, Artur; Vahlenkamp, Thomas; Kaspers, Bernd; Staeheli, Peter

    2011-08-01

    From infection studies with cultured chicken cells and experimental mammalian hosts, it is well known that influenza viruses use the nonstructural protein 1 (NS1) to suppress the synthesis of interferon (IFN). However, our current knowledge regarding the in vivo role of virus-encoded NS1 in chickens is much more limited. Here, we report that highly pathogenic avian influenza viruses of subtypes H5N1 and H7N7 lacking fully functional NS1 genes were attenuated in 5-week-old chickens. Surprisingly, in diseased birds infected with NS1 mutants, the IFN levels were not higher than in diseased birds infected with wild-type virus, suggesting that NS1 cannot suppress IFN gene expression in at least one cell population of infected chickens that produces large amounts of the cytokine in vivo. To address the question of why influenza viruses are highly pathogenic in chickens although they strongly activate the innate immune system, we determined whether recombinant chicken alpha interferon (IFN-α) can inhibit the growth of highly pathogenic avian influenza viruses in cultured chicken cells and whether it can ameliorate virus-induced disease in 5-week-old birds. We found that IFN treatment failed to confer substantial protection against challenge with highly pathogenic viruses, although it was effective against viruses with low pathogenic potential. Taken together, our data demonstrate that preventing the synthesis of IFN is not the primary role of the viral NS1 protein during infection of chickens. Our results further suggest that virus-induced IFN does not contribute substantially to resistance of chickens against highly pathogenic influenza viruses.

  9. Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition

    PubMed Central

    Tate, Michelle D.; Ong, James D. H.; Dowling, Jennifer K.; McAuley, Julie L.; Robertson, Avril B.; Latz, Eicke; Drummond, Grant R.; Cooper, Matthew A.; Hertzog, Paul J.; Mansell, Ashley

    2016-01-01

    The inflammasome NLRP3 is activated by pathogen associated molecular patterns (PAMPs) during infection, including RNA and proteins from influenza A virus (IAV). However, chronic activation by danger associated molecular patterns (DAMPs) can be deleterious to the host. We show that blocking NLRP3 activation can be either protective or detrimental at different stages of lethal influenza A virus (IAV). Administration of the specific NLRP3 inhibitor MCC950 to mice from one day following IAV challenge resulted in hypersusceptibility to lethality. In contrast, delaying treatment with MCC950 until the height of disease (a more likely clinical scenario) significantly protected mice from severe and highly virulent IAV-induced disease. These findings identify for the first time that NLRP3 plays a detrimental role later in infection, contributing to IAV pathogenesis through increased cytokine production and lung cellular infiltrates. These studies also provide the first evidence identifying NLRP3 inhibition as a novel therapeutic target to reduce IAV disease severity. PMID:27283237

  10. Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition.

    PubMed

    Tate, Michelle D; Ong, James D H; Dowling, Jennifer K; McAuley, Julie L; Robertson, Avril B; Latz, Eicke; Drummond, Grant R; Cooper, Matthew A; Hertzog, Paul J; Mansell, Ashley

    2016-01-01

    The inflammasome NLRP3 is activated by pathogen associated molecular patterns (PAMPs) during infection, including RNA and proteins from influenza A virus (IAV). However, chronic activation by danger associated molecular patterns (DAMPs) can be deleterious to the host. We show that blocking NLRP3 activation can be either protective or detrimental at different stages of lethal influenza A virus (IAV). Administration of the specific NLRP3 inhibitor MCC950 to mice from one day following IAV challenge resulted in hypersusceptibility to lethality. In contrast, delaying treatment with MCC950 until the height of disease (a more likely clinical scenario) significantly protected mice from severe and highly virulent IAV-induced disease. These findings identify for the first time that NLRP3 plays a detrimental role later in infection, contributing to IAV pathogenesis through increased cytokine production and lung cellular infiltrates. These studies also provide the first evidence identifying NLRP3 inhibition as a novel therapeutic target to reduce IAV disease severity.

  11. Infection Risk for Persons Exposed to Highly Pathogenic Avian Influenza A H5 Virus-Infected Birds, United States, December 2014-March 2015.

    PubMed

    Arriola, Carmen S; Nelson, Deborah I; Deliberto, Thomas J; Blanton, Lenee; Kniss, Krista; Levine, Min Z; Trock, Susan C; Finelli, Lyn; Jhung, Michael A

    2015-12-01

    Newly emerged highly pathogenic avian influenza (HPAI) A H5 viruses have caused outbreaks among birds in the United States. These viruses differ genetically from HPAI H5 viruses that previously caused human illness, most notably in Asia and Africa. To assess the risk for animal-to-human HPAI H5 virus transmission in the United States, we determined the number of persons with self-reported exposure to infected birds, the number with an acute respiratory infection (ARI) during a 10-day postexposure period, and the number with ARI who tested positive for influenza by real-time reverse transcription PCR or serologic testing for each outbreak during December 15, 2014-March 31, 2015. During 60 outbreaks in 13 states, a total of 164 persons were exposed to infected birds. ARI developed in 5 of these persons within 10 days of exposure. H5 influenza virus infection was not identified in any persons with ARI, suggesting a low risk for animal-to-human HPAI H5 virus transmission.

  12. Infection Risk for Persons Exposed to Highly Pathogenic Avian Influenza A H5 Virus-Infected Birds, United States, December 2014-March 2015.

    PubMed

    Arriola, Carmen S; Nelson, Deborah I; Deliberto, Thomas J; Blanton, Lenee; Kniss, Krista; Levine, Min Z; Trock, Susan C; Finelli, Lyn; Jhung, Michael A

    2015-12-01

    Newly emerged highly pathogenic avian influenza (HPAI) A H5 viruses have caused outbreaks among birds in the United States. These viruses differ genetically from HPAI H5 viruses that previously caused human illness, most notably in Asia and Africa. To assess the risk for animal-to-human HPAI H5 virus transmission in the United States, we determined the number of persons with self-reported exposure to infected birds, the number with an acute respiratory infection (ARI) during a 10-day postexposure period, and the number with ARI who tested positive for influenza by real-time reverse transcription PCR or serologic testing for each outbreak during December 15, 2014-March 31, 2015. During 60 outbreaks in 13 states, a total of 164 persons were exposed to infected birds. ARI developed in 5 of these persons within 10 days of exposure. H5 influenza virus infection was not identified in any persons with ARI, suggesting a low risk for animal-to-human HPAI H5 virus transmission. PMID:26583382

  13. Accumulation of functionally immature myeloid dendritic cells in lymph nodes of rhesus macaques with acute pathogenic simian immunodeficiency virus infection

    PubMed Central

    Wijewardana, Viskam; Bouwer, Anthea L; Brown, Kevin N; Liu, Xiangdong; Barratt-Boyes, Simon M

    2014-01-01

    Myeloid dendritic cells (mDC) are key mediators of innate and adaptive immunity to virus infection, but the impact of HIV infection on the mDC response, particularly early in acute infection, is ill-defined. We studied acute pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques to address this question. The mDC in blood and bone marrow were depleted within 12 days of intravenous infection with SIVmac251, associated with a marked proliferative response. In lymph nodes, mDC were apoptotic, activated and proliferating, despite normal mDC numbers, reflecting a regenerative response that compensated for mDC loss. Blood mDC had increased expression of MHC class II, CCR7 and CD40, whereas in lymph nodes these markers were significantly decreased, indicating that acute infection induced maturation of mDC in blood but resulted in accumulation of immature mDC in lymph nodes. Following SIV infection, lymph node mDC had an increased capacity to secrete tumour necrosis factor-α upon engagement with a Toll-like receptor 7/8 ligand that mimics exposure to viral RNA, and this was inversely correlated with MHC class II and CCR7 expression. Lymph node mDC had an increased ability to capture and cleave soluble antigen, confirming their functionally immature state. These data indicate that acute SIV infection results in increased mDC turnover, leading to accumulation in lymph nodes of immature mDC with an increased responsiveness to virus stimulation. PMID:24684292

  14. Experimental infection with low and high pathogenicity H7N3 Chilean avian influenza viruses in Chiloe Wigeon (Anas sibilatrix) and Cinnamon Teal (Anas cyanoptera)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 2002, H5N1 high pathogenicity avian influenza (HPAI) viruses have been associated with natural, lethal infections in wild aquatic birds which have been reproduced experimentally. Some aquatic bird species have been suggested as potential transporters of H5N1 HPAI virus via migration. However, ...

  15. Impact of vaccination on infection with Vietnam H5N1 high pathogenicity avian influenza virus in hens and the eggs they lay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic avian influenza virus (HPAIV) infections in chickens produce a negative impact on egg production, and virus is deposited on surface and internal contents of eggs. Previously, vaccination maintained egg production and reduced egg contamination when challenged with a North American H...

  16. Risk for infection with highly pathogenic influenza A virus (H5N1) in chickens, Hong Kong, 2002.

    PubMed

    Kung, Nina Y; Morris, Roger S; Perkins, Nigel R; Sims, Les D; Ellis, Trevor M; Bissett, Lucy; Chow, Mary; Shortridge, Ken F; Guan, Yi; Peiris, Malik J S

    2007-03-01

    We used epidemiologic evaluation, molecular epidemiology, and a case-control study to identify possible risk factors for the spread of highly pathogenic avian influenza A virus (subtype H5N1) in chicken farms during the first quarter of 2002 in Hong Kong. Farm profiles, including stock sources, farm management, and biosecurity measures, were collected from 16 case and 46 control chicken farms by using a pretested questionnaire and personal interviews. The risk for influenza A (H5N1) infection was assessed by using adjusted odds ratios based on multivariate logistic regression analysis. Retail marketing of live poultry was implicated as the main source of exposure to infection on chicken farms in Hong Kong during this period. Infection control measures should be reviewed and upgraded as necessary to reduce the spread of influenza A (H5N1) related to live poultry markets, which are commonplace across Asia.

  17. Remarkable sequence similarity between the dinoflagellate-infecting marine girus and the terrestrial pathogen African swine fever virus

    PubMed Central

    Ogata, Hiroyuki; Toyoda, Kensuke; Tomaru, Yuji; Nakayama, Natsuko; Shirai, Yoko; Claverie, Jean-Michel; Nagasaki, Keizo

    2009-01-01

    Heterocapsa circularisquama DNA virus (HcDNAV; previously designated as HcV) is a giant virus (girus) with a ~356-kbp double-stranded DNA (dsDNA) genome. HcDNAV lytically infects the bivalve-killing marine dinoflagellate H. circularisquama, and currently represents the sole DNA virus isolated from dinoflagellates, one of the most abundant protists in marine ecosystems. Its morphological features, genome type, and host range previously suggested that HcDNAV might be a member of the family Phycodnaviridae of Nucleo-Cytoplasmic Large DNA Viruses (NCLDVs), though no supporting sequence data was available. NCLDVs currently include two families found in aquatic environments (Phycodnaviridae, Mimiviridae), one mostly infecting terrestrial animals (Poxviridae), another isolated from fish, amphibians and insects (Iridoviridae), and the last one (Asfarviridae) exclusively represented by the animal pathogen African swine fever virus (ASFV), the agent of a fatal hemorrhagic disease in domestic swine. In this study, we determined the complete sequence of the type B DNA polymerase (PolB) gene of HcDNAV. The viral PolB was transcribed at least from 6 h post inoculation (hpi), suggesting its crucial function for viral replication. Most unexpectedly, the HcDNAV PolB sequence was found to be closely related to the PolB sequence of ASFV. In addition, the amino acid sequence of HcDNAV PolB showed a rare amino acid substitution within a motif containing highly conserved motif: YSDTDS was found in HcDNAV PolB instead of YGDTDS in most dsDNA viruses. Together with the previous observation of ASFV-like sequences in the Sorcerer II Global Ocean Sampling metagenomic datasets, our results further reinforce the ideas that the terrestrial ASFV has its evolutionary origin in marine environments. PMID:19860921

  18. Remarkable sequence similarity between the dinoflagellate-infecting marine girus and the terrestrial pathogen African swine fever virus.

    PubMed

    Ogata, Hiroyuki; Toyoda, Kensuke; Tomaru, Yuji; Nakayama, Natsuko; Shirai, Yoko; Claverie, Jean-Michel; Nagasaki, Keizo

    2009-01-01

    Heterocapsa circularisquama DNA virus (HcDNAV; previously designated as HcV) is a giant virus (girus) with a approximately 356-kbp double-stranded DNA (dsDNA) genome. HcDNAV lytically infects the bivalve-killing marine dinoflagellate H. circularisquama, and currently represents the sole DNA virus isolated from dinoflagellates, one of the most abundant protists in marine ecosystems. Its morphological features, genome type, and host range previously suggested that HcDNAV might be a member of the family Phycodnaviridae of Nucleo-Cytoplasmic Large DNA Viruses (NCLDVs), though no supporting sequence data was available. NCLDVs currently include two families found in aquatic environments (Phycodnaviridae, Mimiviridae), one mostly infecting terrestrial animals (Poxviridae), another isolated from fish, amphibians and insects (Iridoviridae), and the last one (Asfarviridae) exclusively represented by the animal pathogen African swine fever virus (ASFV), the agent of a fatal hemorrhagic disease in domestic swine. In this study, we determined the complete sequence of the type B DNA polymerase (PolB) gene of HcDNAV. The viral PolB was transcribed at least from 6 h post inoculation (hpi), suggesting its crucial function for viral replication. Most unexpectedly, the HcDNAV PolB sequence was found to be closely related to the PolB sequence of ASFV. In addition, the amino acid sequence of HcDNAV PolB showed a rare amino acid substitution within a motif containing highly conserved motif: YSDTDS was found in HcDNAV PolB instead of YGDTDS in most dsDNA viruses. Together with the previous observation of ASFV-like sequences in the Sorcerer II Global Ocean Sampling metagenomic datasets, our results further reinforce the ideas that the terrestrial ASFV has its evolutionary origin in marine environments.

  19. Synergistic effects of sequential infection with highly pathogenic porcine reproductive and respiratory syndrome virus and porcine circovirus type 2

    PubMed Central

    2013-01-01

    Background Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of porcine reproductive and respiratory syndrome (PRRS) and porcine circovirus type 2 (PCV2) is associated with postweaning multisystemic wasting syndrome (PMWS) in pigs. Coinfection with highly pathogenic PRRSV (HP-PRRSV) and PCV2 in the field has recently become extensive in some Asian countries. A synergistic pathogenicity between PRRSV and PCV2 infections has previously been reported. However, the consequences of the sequential infection of pigs with these two viruses are unknown. Methods Thirty 35-day-old piglets were randomly divided into six groups (n = 5 each): HP-PRRSV/PCV2 (group 1, inoculated with HP-PRRSV, then inoculated with PCV2 one week later), PCV2/HP-PRRSV (group 2, inoculated with PCV2, then inoculated with HP-PRRSV one week later), HP-PRRSV+PCV2 (group 3, inoculated with HP-PRRSV and PCV2 concurrently), HP-PRRSV (group 4, inoculated with HP-PRRSV), PCV2 (group 5, inoculated with PCV2), and the control (group 6, uninfected). This experiment lasted 28 days. Clinical symptoms and rectal temperatures were recorded each day after inoculation, body weight was recorded weekly, and serum samples were obtained for viral nucleic acid quantification and antibody titration. Variations in CD3+, CD4+ CD8–, CD3+, CD4–, and CD8+ cells, natural killer (NK) cells, and mononuclear cells were determined by flow cytometry. The serum concentrations of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), and macrophage granulocyte-colony stimulating factor (GM-CSF) were determined. Pathological changes in different tissues from the experimentally infected pigs were recorded. Results The piglets in group 1 had the highest viral loads, the lowest antibody titers, the most-severe clinical signs, and the highest mortality (3/5, 60%; the mortality in the other groups was 0%), and interstitial pneumonia was more severe in this group compare to the

  20. Experimental infection of mallard ducks with different subtype H5 and H7 highly pathogenic avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic avian influenza viruses (HPAIV’s) remain a threat to poultry worldwide. Avian influenza viruses, including HPAIV, are usually non-pathogenic for ducks and other wild aquatic birds, with the exception of some Asian lineage H5N1 HPAIVs which can cause severe disease in ducks. With ...

  1. Resistant Pathogens, Fungi, and Viruses

    PubMed Central

    Guidry, Christopher A.; Mansfield, Sara A.; Sawyer, Robert G.; Cook, Charles H.

    2014-01-01

    The first reports of antibiotic pathogens occurred a few short years after the introduction of these powerful new agents, heralding a new kind of war between medicine and pathogens. Although originally described in Staphylococcus aureus, resistance among bacteria has now become a grim race to determine which classes of bacteria will become more resistant, pitting the Gram positive staphylococci, enterococci, and streptococci against the increasingly resistant Gram negative pathogens, e. g., carbapenemase-resistant enterobacteriaceae. In addition, the availability of antibacterial agents has allowed the development of whole new kinds of diseases caused by non-bacterial pathogens, related largely to fungi that are inherently resistant to antibacterials. All of these organisms are becoming more prevalent and, ultimately, more clinically relevant for surgeons. It is ironic that despite their ubiquity in our communities, there is seldom a second thought given to viral infections in patients with surgical illness. The extent of most surgeon’s interest in viral infections ends with hepatitis and HIV, no doubt related to transmissibility as well as the implications that these viruses might have in a patient’s hepatic or immune functions. There are chapters and even textbooks written about these viruses so these will not be considered here. Instead, we will present the growing body of knowledge of the herpes family viruses and their occurrence and consequences in patients with concomitant surgical disease or critical illness. We have also chosen to focus this chapter on previously immune competent patients, as the impact of herpes family viruses in immunosuppressed patients such as transplant or AIDS patients has received thorough treatment elsewhere. PMID:25440119

  2. Short-Term Heat Shock Affects Host–Virus Interaction in Mice Infected with Highly Pathogenic Avian Influenza Virus H5N1

    PubMed Central

    Xue, Jia; Fan, Xiaoxu; Yu, Jing; Zhang, Shouping; Xiao, Jin; Hu, Yanxin; Wang, Ming

    2016-01-01

    Highly pathogenic avian influenza virus (HPAIV) H5N1 is a highly contagious virus that can cause acute respiratory infections and high human fatality ratio due to excessive inflammatory response. Short-term heat shock, as a stressful condition, could induce the expression of heat shock proteins that function as molecular chaperones to protect cells against multiple stresses. However, the protective effect of short-term heat shock in influenza infection is far from being understood. In this study, mice were treated at 39°C for 4 h before being infected with HPAIV H5N1. Interestingly, short-term heat shock significantly increased the levels of HSP70 and pro-inflammatory cytokines IL-6, TNF-α, IFN-β, and IFN-γ in the lung tissues of mice. Following HPAIV H5N1 infection, short-term heat shock alleviated immunopathology and viral replication in lung tissue and repressed the weight loss and increased the survival rate of H5N1-infected mice. Our data reported that short-term heat shock provided beneficial anti-HPAIV H5N1 properties in mice model, which offers an alternative strategy for non-drug prevention for influenza infection. PMID:27379054

  3. Of Mice and Men: Protective and Pathogenic Immune Responses to West Nile virus Infection

    PubMed Central

    Trobaugh, Derek

    2015-01-01

    West Nile virus, a mosquito-borne flavivirus, first emerged in the Western Hemisphere in 1999. Although the majority of infections are asymptomatic, WNV causes significant morbidity and mortality in a minority of individuals who develop neuroinvasive disease, in particular the elderly and immunocompromised. Research in animal models has demonstrated interactions between WNV and the innate and adaptive immune system, some of which protect the host and others which are deleterious. Studies of disease pathogenesis in humans are less numerous, largely due to the complexities of WNV epidemiology. Human studies that have been done support the notion that innate and adaptive immune responses are delicately balanced and may help or harm the host. Further human investigations are needed to characterize beneficial responses to WNV with the goal of such research leading to therapeutics and effective vaccines in order to control this emerging viral disease. PMID:26120511

  4. Progression of pathogenic events in cynomolgus macaques infected with variola virus.

    PubMed

    Wahl-Jensen, Victoria; Cann, Jennifer A; Rubins, Kathleen H; Huggins, John W; Fisher, Robert W; Johnson, Anthony J; de Kok-Mercado, Fabian; Larsen, Thomas; Raymond, Jo Lynne; Hensley, Lisa E; Jahrling, Peter B

    2011-01-01

    Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

  5. Human infection with a highly pathogenic avian influenza A (H5N6) virus in Yunnan province, China.

    PubMed

    Xu, Wen; Li, Hong; Jiang, Li

    2016-01-01

    Highly pathogenic avian influenza A H5N6 virus has caused four human infections in China. This study reports the preliminary findings of the first known human case of H5N6 in Yunnan province. The patient initially developed symptoms of sore throat and coughing on 27 January 2015. The disease rapidly progressed to severe pneumonia, multiple organ dysfunctions and acute respiratory distress syndrome and the patient died on 6 February. Virological analysis determined that the virus belonged to H5 clade 2.3.4.4 and it has obtained partial ability for mammalian adaptation and amantadine resistance. Environmental investigation found H5 in 63% of the samples including poultry faeces, tissues, cage surface swabs and sewage from local live poultry markets by real-time RT-PCR. These findings suggest that the expanding and enhancing of surveillance in both avian and humans are necessary to monitor the evolution of H5 influenza virus and to facilitate early detection of suspected cases. PMID:27030920

  6. Previous infection with virulent strains of Newcastle disease virus reduces highly pathogenic avian influenza virus replication, disease, and mortality in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) and Newcastle disease virus (NDV) are two of the most important viruses affecting poultry worldwide, but little is known about the interaction between these two viruses when simultaneously co-infecting the same host, especially in areas of the world where both viruses are...

  7. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection. PMID:27486731

  8. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection.

  9. Replication of 2 subtypes of low-pathogenicity avian influenza virus of duck and gull origins in experimentally infected Mallard ducks.

    PubMed

    Daoust, P-Y; van de Bildt, M; van Riel, D; van Amerongen, G; Bestebroer, T; Vanderstichel, R; Fouchier, R A M; Kuiken, T

    2013-05-01

    Many subtypes of low-pathogenicity avian influenza (LPAI) virus circulate in wild bird reservoirs, but their prevalence may vary among species. We aimed to compare by real-time reverse-transcriptase polymerase chain reaction, virus isolation, histology, and immunohistochemistry the distribution and pathogenicity of 2 such subtypes of markedly different origins in Mallard ducks (Anas platyrhynchos): H2N3 isolated from a Mallard duck and H13N6 isolated from a Ring-billed Gull (Larus delawarensis). Following intratracheal and intraesophageal inoculation, neither virus caused detectable clinical signs, although H2N3 virus infection was associated with a significantly decreased body weight gain during the period of virus shedding. Both viruses replicated in the lungs and air sacs until approximately day 3 after inoculation and were associated with a locally extensive interstitial, exudative, and proliferative pneumonia. Subtype H2N3, but not subtype H13N6, went on to infect the epithelia of the intestinal mucosa and cloacal bursa, where it replicated without causing lesions until approximately day 5 after inoculation. Larger quantities of subtype H2N3 virus were detected in cloacal swabs than in pharyngeal swabs. The possible clinical significance of LPAI virus-associated pulmonary lesions and intestinal tract infection in ducks deserves further evaluation.

  10. Long-Term Effect of Serial Infections with H13 and H16 Low-Pathogenic Avian Influenza Viruses in Black-Headed Gulls

    PubMed Central

    Verhagen, Josanne H.; van Amerongen, Geert; van de Bildt, Marco; Majoor, Frank; Fouchier, Ron A. M.

    2015-01-01

    ABSTRACT Infections of domestic and wild birds with low-pathogenic avian influenza viruses (LPAIVs) have been associated with protective immunity to subsequent infection. However, the degree and duration of immunity in wild birds from previous LPAIV infection, by the same or a different subtype, are poorly understood. Therefore, we inoculated H13N2 (A/black-headed gull/Netherlands/7/2009) and H16N3 (A/black-headed gull/Netherlands/26/2009) LPAIVs into black-headed gulls (Chroicocephalus ridibundus), their natural host species, and measured the long-term immune response and protection against one or two reinfections over a period of >1 year. This is the typical interval between LPAIV epizootics in wild birds. Reinfection with the same virus resulted in progressively less virus excretion, with complete abrogation of virus excretion after two infections for H13 but not H16. However, reinfection with the other virus affected neither the level nor duration of virus excretion. Virus excretion by immunologically naive birds did not differ in total levels of excreted H13 or H16 virus between first- and second-year birds, but the duration of H13 excretion was shorter for second-year birds. Furthermore, serum antibody levels did not correlate with protection against LPAIV infection. LPAIV-infected gulls showed no clinical signs of disease. These results imply that the epidemiological cycles of H13 and H16 in black-headed gulls are relatively independent from each other and depend mainly on infection of first-year birds. IMPORTANCE Low-pathogenic avian influenza viruses (LPAIVs) circulate mainly in wild water birds but are occasionally transmitted to other species, including humans, where they cause subclinical to fatal disease. To date, the effect of LPAIV-specific immunity on the epidemiology of LPAIV in wild birds is poorly understood. In this study, we investigated the effect of H13 and H16 LPAIV infection in black-headed gulls on susceptibility and virus excretion of

  11. Histopathological characterization and shedding dynamics of guineafowl (Numida meleagris) intravenously infected with a H6N2 low pathogenicity Avian Influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Guineafowl of different ages were inoculated intravenously with an H6N2 wild waterfowl-origin low-pathogenicity type A avian influenza virus (LPAI). No evidence of clinical disease was observed. The examined infected birds had atrophy of the spleen, thymus, and cloacal bursa when compared to the n...

  12. Impact of vaccination on infection with Vietnam H5N1 high pathogenicity avian influenza virus in hens and the eggs they lay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High pathogenicity avian influenza virus (HPAIV) infections in chickens decrease egg production and eggs that are laid contain HPAIV. Vaccination once or twice was examined as a way to protect chickens from Vietnamese H5N1 HPAIV. Eighty-three percent of hens without vaccination died within 3 days ...

  13. Experimental co-infection of chickens with lentogenic, mesogenic and velogenic strains of Newcastle disease viruses and highly pathogenic avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Avian influenza virus (AIV) and Newcastle disease virus (NDV) are two of the most economically important viruses affecting poultry worldwide. Co-infections of poultry with AIV and NDV are a problem from the clinical point of view and diagnosis of these viruses, but little is known on t...

  14. Host antiviral defenses induced by a mesogenic strain of Newcastle disease virus prevents infection with a highly pathogenic avian influenza virus in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) and Newcastle disease virus (NDV) are two of the most important viruses affecting poultry worldwide. Co-infections of poultry with AIV and NDV are a problem from both the clinical point of view and the diagnosis of these viruses. To evaluate the dynamics of AIV-NDV co-i...

  15. Early events in tissues during infection with pathogenic (SIVmac239) and nonpathogenic (SIVmac1A11) molecular clones of simian immunodeficiency virus.

    PubMed Central

    Lackner, A. A.; Vogel, P.; Ramos, R. A.; Kluge, J. D.; Marthas, M.

    1994-01-01

    The extent of virus replication, tissue distribution, localization of virus within tissues, and the presence of pathological lesions was examined early after experimental infection of rhesus monkeys with simian immunodeficiency virus (SIV). Three strains of SIV were used: molecularly cloned pathogenic SIVmac239; molecularly cloned nonpathogenic SIVmac1A11; and uncloned pathogenic SIVmac. The major targets of infection in all animals at 2 weeks postinoculation were the thymus and spleen. The distribution of virus within lymphoid organs varied with the viral inoculum: nonpathogenic SIVmac1A11 was present primarily within lymphoid follicles and in the thymic cortex; SIVmac239 was present primarily within periarteriolar lymphoid sheaths in the spleen, the paracortex of lymph nodes, and the medulla of the thymus; uncloned SIVmac was present in all these areas but tended to parallel the distribution of SIVmac239. Animals inoculated with nonpathogenic SIVmac1A11 had fewer SIV-positive cells by in situ hybridization and after 13 weeks postinoculation, virus was undetectable in any tissue from these animals. No significant pathological abnormalities were recognized in animals inoculated with this nonpathogenic virus. In contrast, nearly half of the animals inoculated with either SIVmac or SIVmac239 developed significant pathological lesions, including opportunistic infections by 13 weeks postinoculation, highlighting the virulence of these viruses. Our results indicate marked differences in tissue distribution between pathogenic and nonpathogenic molecular clones of SIV during the acute phase of infection. The most striking differences were the absence of SIVmac1A11 from the central nervous system and thymic medulla. The prominent early involvement of the thymus suggests that infection of this organ is a key event in the induction of immune suppression by SIV. Images Figure 1 Figure 2 Figure 3 PMID:8053500

  16. Viral replication rate regulates clinical outcome and CD8 T cell responses during highly pathogenic H5N1 influenza virus infection in mice.

    PubMed

    Hatta, Yasuko; Hershberger, Karen; Shinya, Kyoko; Proll, Sean C; Dubielzig, Richard R; Hatta, Masato; Katze, Michael G; Kawaoka, Yoshihiro; Suresh, M

    2010-01-01

    Since the first recorded infection of humans with H5N1 viruses of avian origin in 1997, sporadic human infections continue to occur with a staggering mortality rate of >60%. Although sustained human-to-human transmission has not occurred yet, there is a growing concern that these H5N1 viruses might acquire this trait and raise the specter of a pandemic. Despite progress in deciphering viral determinants of pathogenicity, we still lack crucial information on virus/immune system interactions pertaining to severe disease and high mortality associated with human H5N1 influenza virus infections. Using two human isolates of H5N1 viruses that differ in their pathogenicity in mice, we have defined mechanistic links among the rate of viral replication, mortality, CD8 T cell responses, and immunopathology. The extreme pathogenicity of H5N1 viruses was directly linked to the ability of the virus to replicate rapidly, and swiftly attain high steady-state titers in the lungs within 48 hours after infection. The remarkably high replication rate of the highly pathogenic H5N1 virus did not prevent the induction of IFN-β or activation of CD8 T cells, but the CD8 T cell response was ineffective in controlling viral replication in the lungs and CD8 T cell deficiency did not affect viral titers or mortality. Additionally, BIM deficiency ameliorated lung pathology and inhibited T cell apoptosis without affecting survival of mice. Therefore, rapidly replicating, highly lethal H5N1 viruses could simply outpace and overwhelm the adaptive immune responses, and kill the host by direct cytopathic effects. However, therapeutic suppression of early viral replication and the associated enhancement of CD8 T cell responses improved the survival of mice following a lethal H5N1 infection. These findings suggest that suppression of early H5N1 virus replication is key to the programming of an effective host response, which has implications in treatment of this infection in humans. PMID:20949022

  17. Disease Severity Is Associated with Differential Gene Expression at the Early and Late Phases of Infection in Nonhuman Primates Infected with Different H5N1 Highly Pathogenic Avian Influenza Viruses

    PubMed Central

    Muramoto, Yukiko; Shoemaker, Jason E.; Le, Mai Quynh; Itoh, Yasushi; Tamura, Daisuke; Sakai-Tagawa, Yuko; Imai, Hirotaka; Uraki, Ryuta; Takano, Ryo; Kawakami, Eiryo; Ito, Mutsumi; Okamoto, Kiyoko; Ishigaki, Hirohito; Mimuro, Hitomi; Sasakawa, Chihiro; Matsuoka, Yukiko; Noda, Takeshi; Fukuyama, Satoshi; Ogasawara, Kazumasa; Kitano, Hiroaki

    2014-01-01

    ABSTRACT Occasional transmission of highly pathogenic avian H5N1 influenza viruses to humans causes severe pneumonia with high mortality. To better understand the mechanisms via which H5N1 viruses induce severe disease in humans, we infected cynomolgus macaques with six different H5N1 strains isolated from human patients and compared their pathogenicity and the global host responses to the virus infection. Although all H5N1 viruses replicated in the respiratory tract, there was substantial heterogeneity in their replicative ability and in the disease severity induced, which ranged from asymptomatic to fatal. A comparison of global gene expression between severe and mild disease cases indicated that interferon-induced upregulation of genes related to innate immunity, apoptosis, and antigen processing/presentation in the early phase of infection was limited in severe disease cases, although interferon expression was upregulated in both severe and mild cases. Furthermore, coexpression analysis of microarray data, which reveals the dynamics of host responses during the infection, demonstrated that the limited expression of these genes early in infection led to a failure to suppress virus replication and to the hyperinduction of genes related to immunity, inflammation, coagulation, and homeostasis in the late phase of infection, resulting in a more severe disease. Our data suggest that the attenuated interferon-induced activation of innate immunity, apoptosis, and antigen presentation in the early phase of H5N1 virus infection leads to subsequent severe disease outcome. IMPORTANCE Highly pathogenic avian H5N1 influenza viruses sometimes transmit to humans and cause severe pneumonia with ca. 60% lethality. The continued circulation of these viruses poses a pandemic threat; however, their pathogenesis in mammals is not fully understood. We, therefore, investigated the pathogenicity of six H5N1 viruses and compared the host responses of cynomolgus macaques to the virus

  18. Persistence of highly pathogenic avian influenza virus (H7N1) in infected chickens: feather as a suitable sample for diagnosis.

    PubMed

    Busquets, Núria; Abad, F Xavier; Alba, Anna; Dolz, Roser; Allepuz, Alberto; Rivas, Raquel; Ramis, Antonio; Darji, Ayub; Majó, Natàlia

    2010-09-01

    Selection of an ideal sample is a vital element in early detection of influenza infection. Rapid identification of infectious individuals or animals is crucial not only for avian influenza virus (AIV) surveillance programmes, but also for treatment and containment strategies. This study used a combination of quantitative real-time RT-PCR with an internal positive control and a cell-titration system to examine the presence of virus in different samples during active experimental AIV infection and its persistence in the infected carcasses. Oropharyngeal/cloacal swabs as well as feather pulp and blood samples were collected from 15-day-old chicks infected with H7N1 highly pathogenic AIV (HPAIV) and the kinetics of virus shedding during active infection were evaluated. Additionally, several samples (muscle, skin, brain, feather pulp and oropharyngeal and cloacal swabs) were examined to assess the persistence of virus in the HPAIV-infected carcasses. Based on the results, feather pulp was found to be the best sample to detect and isolate HPAIV from infected chicks from 24 h after inoculation onwards. Kinetic studies on the persistence of virus in infected carcasses revealed that tissues such as muscle could potentially transmit infectious virus for 3 days post-mortem (p.m.), whilst other tissues such as skin, feather pulp and brain retained their infectivity for as long as 5-6 days p.m. at environmental temperature (22-23 degrees C). These results strongly favour feather as a useful sample for HPAIV diagnosis in infected chickens as well as in carcasses.

  19. Encephalitis in a stone marten (Martes foina) after natural infection with highly pathogenic avian influenza virus subtype H5N1.

    PubMed

    Klopfleisch, R; Wolf, P U; Wolf, C; Harder, T; Starick, E; Niebuhr, M; Mettenleiter, T C; Teifke, J P

    2007-01-01

    Recent outbreaks of disease in different avian species, caused by the highly pathogenic avian influenza virus (HPAIV), have involved infection by subtype H5N1 of the virus. This virus has also crossed species barriers and infected felines and humans. Here, we report the natural infection of a stone marten (Martes foina) from an area with numerous confirmed cases of H5N1 HPAIV infection in wild birds. Histopathological examination of tissues from this animal revealed a diffuse nonsuppurative panencephalitis with perivascular cuffing, multifocal gliosis and neuronal necrosis. Additionally, focal necrosis of pancreatic acinar cells was observed. Immunohistochemically, lesions in these organs were associated with avian influenza virus antigen in neurons, glial cells and pancreatic acinar cells. Thus, the microscopical lesions and viral antigen distribution in this stone marten differs from that recently described for cats naturally and experimentally infected with the same virus subtype. This is the first report of natural infection of a mustelid with HPAIV H5N1.

  20. Survival analysis of infected mice reveals pathogenic variations in the genome of avian H1N1 viruses

    PubMed Central

    Koçer, Zeynep A.; Fan, Yiping; Huether, Robert; Obenauer, John; Webby, Richard J.; Zhang, Jinghui; Webster, Robert G.; Wu, Gang

    2014-01-01

    Most influenza pandemics have been caused by H1N1 viruses of purely or partially avian origin. Here, using Cox proportional hazard model, we attempt to identify the genetic variations in the whole genome of wild-type North American avian H1N1 influenza A viruses that are associated with their virulence in mice by residue variations, host origins of virus (Anseriformes-ducks or Charadriiformes-shorebirds), and host-residue interactions. In addition, through structural modeling, we predicted that several polymorphic sites associated with pathogenicity were located in structurally important sites, especially in the polymerase complex and NS genes. Our study introduces a new approach to identify pathogenic variations in wild-type viruses circulating in the natural reservoirs and ultimately to understand their infectious risks to humans as part of risk assessment efforts towards the emergence of future pandemic strains. PMID:25503687

  1. Experimentally Infected Domestic Ducks Show Efficient Transmission of Indonesian H5N1 Highly Pathogenic Avian Influenza Virus, but Lack Persistent Viral Shedding

    PubMed Central

    Wibawa, Hendra; Bingham, John; Nuradji, Harimurti; Lowther, Sue; Payne, Jean; Harper, Jenni; Junaidi, Akhmad; Middleton, Deborah; Meers, Joanne

    2014-01-01

    Ducks are important maintenance hosts for avian influenza, including H5N1 highly pathogenic avian influenza viruses. A previous study indicated that persistence of H5N1 viruses in ducks after the development of humoral immunity may drive viral evolution following immune selection. As H5N1 HPAI is endemic in Indonesia, this mechanism may be important in understanding H5N1 evolution in that region. To determine the capability of domestic ducks to maintain prolonged shedding of Indonesian clade 2.1 H5N1 virus, two groups of Pekin ducks were inoculated through the eyes, nostrils and oropharynx and viral shedding and transmission investigated. Inoculated ducks (n = 15), which were mostly asymptomatic, shed infectious virus from the oral route from 1 to 8 days post inoculation, and from the cloacal route from 2–8 dpi. Viral ribonucleic acid was detected from 1–15 days post inoculation from the oral route and 1–24 days post inoculation from the cloacal route (cycle threshold <40). Most ducks seroconverted in a range of serological tests by 15 days post inoculation. Virus was efficiently transmitted during acute infection (5 inoculation-infected to all 5 contact ducks). However, no evidence for transmission, as determined by seroconversion and viral shedding, was found between an inoculation-infected group (n = 10) and contact ducks (n = 9) when the two groups only had contact after 10 days post inoculation. Clinical disease was more frequent and more severe in contact-infected (2 of 5) than inoculation-infected ducks (1 of 15). We conclude that Indonesian clade 2.1 H5N1 highly pathogenic avian influenza virus does not persist in individual ducks after acute infection. PMID:24392085

  2. Experimentally infected domestic ducks show efficient transmission of Indonesian H5N1 highly pathogenic avian influenza virus, but lack persistent viral shedding.

    PubMed

    Wibawa, Hendra; Bingham, John; Nuradji, Harimurti; Lowther, Sue; Payne, Jean; Harper, Jenni; Junaidi, Akhmad; Middleton, Deborah; Meers, Joanne

    2014-01-01

    Ducks are important maintenance hosts for avian influenza, including H5N1 highly pathogenic avian influenza viruses. A previous study indicated that persistence of H5N1 viruses in ducks after the development of humoral immunity may drive viral evolution following immune selection. As H5N1 HPAI is endemic in Indonesia, this mechanism may be important in understanding H5N1 evolution in that region. To determine the capability of domestic ducks to maintain prolonged shedding of Indonesian clade 2.1 H5N1 virus, two groups of Pekin ducks were inoculated through the eyes, nostrils and oropharynx and viral shedding and transmission investigated. Inoculated ducks (n = 15), which were mostly asymptomatic, shed infectious virus from the oral route from 1 to 8 days post inoculation, and from the cloacal route from 2-8 dpi. Viral ribonucleic acid was detected from 1-15 days post inoculation from the oral route and 1-24 days post inoculation from the cloacal route (cycle threshold <40). Most ducks seroconverted in a range of serological tests by 15 days post inoculation. Virus was efficiently transmitted during acute infection (5 inoculation-infected to all 5 contact ducks). However, no evidence for transmission, as determined by seroconversion and viral shedding, was found between an inoculation-infected group (n = 10) and contact ducks (n = 9) when the two groups only had contact after 10 days post inoculation. Clinical disease was more frequent and more severe in contact-infected (2 of 5) than inoculation-infected ducks (1 of 15). We conclude that Indonesian clade 2.1 H5N1 highly pathogenic avian influenza virus does not persist in individual ducks after acute infection.

  3. Molecular Signatures Associated with Mx1-Mediated Resistance to Highly Pathogenic Influenza Virus Infection: Mechanisms of Survival

    PubMed Central

    Cilloniz, Cristian; Pantin-Jackwood, Mary J.; Ni, Chester; Carter, Victoria S.; Korth, Marcus J.; Swayne, David E.; Tumpey, Terrence M.

    2012-01-01

    Understanding the role of host factors during lethal influenza virus infection is critical to deciphering the events that determine the fate of the host. One such factor is encoded by the Mx1 gene, which confers resistance to influenza virus infection. Here, we compared pathology and global gene expression profiles in lung tissue from BALB/c (Mx1−) and BALB · A2G-Mx1 mice (Mx1+/+) infected with the fully reconstructed 1918 pandemic influenza virus. Mx1+/+ mice showed less tissue damage than Mx− animals, and pathology and mortality were further reduced by treating the mice with interferon prior to infection. Using global transcriptional profiling, we identified distinct molecular signatures associated with partial protection, complete protection, and the contribution of interferon to the host response. In the absence of interferon treatment, partial protection was characterized by the generation of an acute response with the upregulation of genes associated with apoptosis, reactive oxygen species, and cell migration. Complete protection was characterized by the downregulation of cytokine and chemokine genes previously associated with influenza virus pathogenesis. The contribution of interferon treatment to total protection in virus-infected Mx1+/+ mice was characterized by the altered regulation of cell cycle genes. These genes were upregulated in Mx1+/+ mice treated with interferon but downregulated in the absence of interferon treatment. Our results suggest that Mx1+/+ mice generate a protective antiviral response by controlling the expression of key modulator molecules associated with influenza virus lethality. PMID:22190720

  4. Experimental infection of bar-headed geese (Anser indicus) and ruddy shelducks (Tadorna ferruginea) with a clade 2.3.2 H5N1 highly pathogenic avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 2005, clade 2.2 H5N1 highly pathogenic avian influenza (HPAI) viruses have caused infections and disease involving numerous species of wild waterfowl in Eurasia and Africa. However, outbreaks associated with clade 2.3.2 viruses have increased since 2009, and viruses within this clade have beco...

  5. Utilizing virus-induced gene silencing for the functional characterization of maize genes during infection with the fungal pathogen Ustilago maydis.

    PubMed

    van der Linde, Karina; Doehlemann, Gunther

    2013-01-01

    While in dicotyledonous plants virus-induced gene silencing (VIGS) is well established to study plant-pathogen interaction, in monocots only few examples of efficient VIGS have been reported so far. One of the available systems is based on the brome mosaic virus (BMV) which allows gene silencing in different cereals including barley (Hordeum vulgare), wheat (Triticum aestivum), and maize (Zea mays).Infection of maize plants by the corn smut fungus Ustilago maydis leads to the formation of large tumors on stem, leaves, and inflorescences. During this biotrophic interaction, plant defense responses are actively suppressed by the pathogen, and previous transcriptome analyses of infected maize plants showed comprehensive and stage-specific changes in host gene expression during disease progression.To identify maize genes that are functionally involved in the interaction with U. maydis, we adapted a VIGS system based on the Brome mosaic virus (BMV) to maize at conditions that allow successful U. maydis infection of BMV pre-infected maize plants. This setup enables quantification of VIGS and its impact on U. maydis infection using a quantitative real-time PCR (q(RT)-PCR)-based readout.

  6. Pathologic Changes in Wild Birds Infected with Highly Pathogenic Avian Influenza A(H5N8) Viruses, South Korea, 2014.

    PubMed

    Kim, Hye-Ryoung; Kwon, Yong-Kuk; Jang, Il; Lee, Youn-Jeong; Kang, Hyun-Mi; Lee, Eun-Kyoung; Song, Byung-Min; Lee, Hee-Soo; Joo, Yi-Seok; Lee, Kyung-Hyun; Lee, Hyun-Kyoung; Baek, Kang-Hyun; Bae, You-Chan

    2015-05-01

    In January 2014, an outbreak of infection with highly pathogenic avian influenza (HPAI) A(H5N8) virus began on a duck farm in South Korea and spread to other poultry farms nearby. During this outbreak, many sick or dead wild birds were found around habitats frequented by migratory birds. To determine the causes of death, we examined 771 wild bird carcasses and identified HPAI A(H5N8) virus in 167. Gross and histologic lesions were observed in pancreas, lung, brain, and kidney of Baikal teals, bean geese, and whooper swans but not mallard ducks. Such lesions are consistent with lethal HPAI A(H5N8) virus infection. However, some HPAI-positive birds had died of gunshot wounds, peritonitis, or agrochemical poisoning rather than virus infection. These findings suggest that susceptibility to HPAI A(H5N8) virus varies among species of migratory birds and that asymptomatic migratory birds could be carriers of this virus.

  7. Pathologic Changes in Wild Birds Infected with Highly Pathogenic Avian Influenza A(H5N8) Viruses, South Korea, 2014

    PubMed Central

    Kim, Hye-Ryoung; Kwon, Yong-Kuk; Jang, Il; Lee, Youn-Jeong; Kang, Hyun-Mi; Lee, Eun-Kyoung; Song, Byung-Min; Lee, Hee-Soo; Joo, Yi-Seok; Lee, Kyung-Hyun; Lee, Hyun-Kyoung; Baek, Kang-Hyun

    2015-01-01

    In January 2014, an outbreak of infection with highly pathogenic avian influenza (HPAI) A(H5N8) virus began on a duck farm in South Korea and spread to other poultry farms nearby. During this outbreak, many sick or dead wild birds were found around habitats frequented by migratory birds. To determine the causes of death, we examined 771 wild bird carcasses and identified HPAI A(H5N8) virus in 167. Gross and histologic lesions were observed in pancreas, lung, brain, and kidney of Baikal teals, bean geese, and whooper swans but not mallard ducks. Such lesions are consistent with lethal HPAI A(H5N8) virus infection. However, some HPAI-positive birds had died of gunshot wounds, peritonitis, or agrochemical poisoning rather than virus infection. These findings suggest that susceptibility to HPAI A(H5N8) virus varies among species of migratory birds and that asymptomatic migratory birds could be carriers of this virus. PMID:25897841

  8. Metagenomic Detection of Viral Pathogens in Spanish Honeybees: Co-Infection by Aphid Lethal Paralysis, Israel Acute Paralysis and Lake Sinai Viruses

    PubMed Central

    Rubio-Guerri, Consuelo; Karlsson, Oskar E.; Kukielka, Deborah; Belák, Sándor; Sánchez-Vizcaíno, José Manuel

    2013-01-01

    The situation in Europe concerning honeybees has in recent years become increasingly aggravated with steady decline in populations and/or catastrophic winter losses. This has largely been attributed to the occurrence of a variety of known and “unknown”, emerging novel diseases. Previous studies have demonstrated that colonies often can harbour more than one pathogen, making identification of etiological agents with classical methods difficult. By employing an unbiased metagenomic approach, which allows the detection of both unexpected and previously unknown infectious agents, the detection of three viruses, Aphid Lethal Paralysis Virus (ALPV), Israel Acute Paralysis Virus (IAPV), and Lake Sinai Virus (LSV), in honeybees from Spain is reported in this article. The existence of a subgroup of ALPV with the ability to infect bees was only recently reported and this is the first identification of such a strain in Europe. Similarly, LSV appear to be a still unclassified group of viruses with unclear impact on colony health and these viruses have not previously been identified outside of the United States. Furthermore, our study also reveals that these bees carried a plant virus, Turnip Ringspot Virus (TuRSV), potentially serving as important vector organisms. Taken together, these results demonstrate the new possibilities opened up by high-throughput sequencing and metagenomic analysis to study emerging new diseases in domestic and wild animal populations, including honeybees. PMID:23460860

  9. Experimental infection of highly and low pathogenic avian influenza viruses to chickens, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission.

    PubMed

    Hiono, Takahiro; Okamatsu, Masatoshi; Yamamoto, Naoki; Ogasawara, Kohei; Endo, Mayumi; Kuribayashi, Saya; Shichinohe, Shintaro; Motohashi, Yurie; Chu, Duc-Huy; Suzuki, Mizuho; Ichikawa, Takaya; Nishi, Tatsuya; Abe, Yuri; Matsuno, Keita; Tanaka, Kazuyuki; Tanigawa, Tsutomu; Kida, Hiroshi; Sakoda, Yoshihiro

    2016-01-01

    Highly pathogenic avian influenza viruses (HPAIVs) have spread in both poultry and wild birds. Determining transmission routes of these viruses during an outbreak is essential for the control of avian influenza. It has been widely postulated that migratory ducks play crucial roles in the widespread dissemination of HPAIVs in poultry by carrying viruses along with their migrations; however close contacts between wild migratory ducks and poultry are less likely in modern industrial poultry farming settings. Therefore, we conducted experimental infections of HPAIVs and low pathogenic avian influenza viruses (LPAIVs) to chickens, domestic ducks, tree sparrows, jungle crows, and black rats to evaluate their roles in virus transmission. The results showed that chickens, ducks, sparrows, and crows were highly susceptible to HPAIV infection. Significant titers of virus were recovered from the sparrows and crows infected with HPAIVs, which suggests that they potentially play roles of transmission of HPAIVs to poultry. In contrast, the growth of LPAIVs was limited in each of the animals tested compared with that of HPAIVs. The present results indicate that these common synanthropes play some roles in influenza virus transmission from wild birds to poultry.

  10. Experimental infection of highly and low pathogenic avian influenza viruses to chickens, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission.

    PubMed

    Hiono, Takahiro; Okamatsu, Masatoshi; Yamamoto, Naoki; Ogasawara, Kohei; Endo, Mayumi; Kuribayashi, Saya; Shichinohe, Shintaro; Motohashi, Yurie; Chu, Duc-Huy; Suzuki, Mizuho; Ichikawa, Takaya; Nishi, Tatsuya; Abe, Yuri; Matsuno, Keita; Tanaka, Kazuyuki; Tanigawa, Tsutomu; Kida, Hiroshi; Sakoda, Yoshihiro

    2016-01-15

    Highly pathogenic avian influenza viruses (HPAIVs) have spread in both poultry and wild birds. Determining transmission routes of these viruses during an outbreak is essential for the control of avian influenza. It has been widely postulated that migratory ducks play crucial roles in the widespread dissemination of HPAIVs in poultry by carrying viruses along with their migrations; however close contacts between wild migratory ducks and poultry are less likely in modern industrial poultry farming settings. Therefore, we conducted experimental infections of HPAIVs and low pathogenic avian influenza viruses (LPAIVs) to chickens, domestic ducks, tree sparrows, jungle crows, and black rats to evaluate their roles in virus transmission. The results showed that chickens, ducks, sparrows, and crows were highly susceptible to HPAIV infection. Significant titers of virus were recovered from the sparrows and crows infected with HPAIVs, which suggests that they potentially play roles of transmission of HPAIVs to poultry. In contrast, the growth of LPAIVs was limited in each of the animals tested compared with that of HPAIVs. The present results indicate that these common synanthropes play some roles in influenza virus transmission from wild birds to poultry. PMID:26711036

  11. Duck MDA5 functions in innate immunity against H5N1 highly pathogenic avian influenza virus infections.

    PubMed

    Wei, Liangmeng; Cui, Jin; Song, Yafen; Zhang, Shuo; Han, Fei; Yuan, Runyu; Gong, Lang; Jiao, Peirong; Liao, Ming

    2014-01-01

    Melanoma differentiation-associated gene 5 (MDA5) is an important intracellular receptor that recognizes long molecules of viral double-stranded RNA in innate immunity. To understand the mechanism of duck MDA5-mediated innate immunity, we cloned the MDA5 cDNA from the Muscovy duck (Cairina moschata). Quantitative real-time PCR analysis indicates that duck MDA5 mRNA was constitutively expressed in all sampled tissues. A significant increase of MDA5 mRNA was detected in the brain, spleen and lungs of ducks after infection with an H5N1 highly pathogenic avian influenza virus (HPAIV). We investigated the role of the predicted functional domains of MDA5. The results indicate the caspase activation and recruitment domain (CARD) of duck MDA5 had a signal transmission function through IRF-7-dependent signaling pathway. Overexpression of the CARD strongly activated the chicken IFN-β promoter and upregulated the mRNA expression of antiviral molecules (such as OAS, PKR and Mx), proinflammatory cytokines (such as IL-2, IL-6, IFN-α and IFN-γ, but not IL-1β and IL-8) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) (RIG-I and LGP2) without exogenous stimulation. We also demonstrate the NS1 of the H5N1 HPAIV inhibited the duck MDA5-mediated signaling pathway in vitro. These results suggest that duck MDA5 is an important receptor for inducing antiviral activity in the host immune response of ducks.

  12. Pathogenicity of an H5N1 avian influenza virus isolated in Vietnam in 2012 and reliability of conjunctival samples for diagnosis of infection

    PubMed Central

    Bui, Vuong N.; Dao, Tung D.; Nguyen, Tham T. H.; Nguyen, Lien T.; Bui, Anh N.; Trinh, Dai Q.; Pham, Nga T.; Inui, Kenjiro; Runstadler, Jonathan; Ogawa, Haruko; Nguyen, Khong V.; Imai, Kunitoshi

    2013-01-01

    The continued spread of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 among poultry in Vietnam poses a potential threat to animals and public health. To evaluate the pathogenicity of a 2012 H5N1 HPAIV isolate and to assess the utility of conjunctival swabs for viral detection and isolation in surveillance, an experimental infection with HPAIV subtype H5N1 was carried out in domestic ducks. Ducks were infected with 107.2 TCID50 of A/duck/Vietnam/QB1207/2012 (H5N1), which was isolated from a moribund domestic duck. In the infected ducks, clinical signs of disease, including neurological disorder, were observed. Ducks started to die at 3 days-post-infection (dpi), and the study mortality reached 67%. Viruses were recovered from oropharyngeal and conjunctival swabs until 7 dpi and from cloacal swabs until 4 dpi. In the ducks that died or were sacrificed on 3, 5, or 6 dpi, viruses were recovered from lung, brain, heart, pancreas and intestine, among which the highest virus titers were in the lung, brain or heart. Results of virus titration were confirmed by real-time RT-PCR. Genetic and phylogenetic analysis of the HA gene revealed that the isolate belongs to clade 2.3.2.1 similarly to the H5N1 viruses isolated in Vietnam in 2012. The present study demonstrated that this recent HPAI H5N1 virus of clade 2.3.2.1 could replicate efficiently in the systemic organs, including the brain, and cause severe disease with neurological symptoms in domestic ducks. Therefore, this HPAI H5N1 virus seems to retain the neurotrophic feature and has further developed properties of shedding virus from the oropharynx and conjunctiva in addition to the cloaca, potentially posing a higher risk of virus spread through cross-contact and/or environmental transmission. Continued surveillance and diagnostic programs using conjuntcival swabs in the field would further verify the apparent reliability of conjunctival samples for the detection of AIV. PMID:24211664

  13. Pathogenicity of an H5N1 avian influenza virus isolated in Vietnam in 2012 and reliability of conjunctival samples for diagnosis of infection.

    PubMed

    Bui, Vuong N; Dao, Tung D; Nguyen, Tham T H; Nguyen, Lien T; Bui, Anh N; Trinh, Dai Q; Pham, Nga T; Inui, Kenjiro; Runstadler, Jonathan; Ogawa, Haruko; Nguyen, Khong V; Imai, Kunitoshi

    2014-01-22

    The continued spread of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 among poultry in Vietnam poses a potential threat to animals and public health. To evaluate the pathogenicity of a 2012 H5N1 HPAIV isolate and to assess the utility of conjunctival swabs for viral detection and isolation in surveillance, an experimental infection with HPAIV subtype H5N1 was carried out in domestic ducks. Ducks were infected with 10(7.2) TCID50 of A/duck/Vietnam/QB1207/2012 (H5N1), which was isolated from a moribund domestic duck. In the infected ducks, clinical signs of disease, including neurological disorder, were observed. Ducks started to die at 3 days-post-infection (dpi), and the study mortality reached 67%. Viruses were recovered from oropharyngeal and conjunctival swabs until 7 dpi and from cloacal swabs until 4 dpi. In the ducks that died or were sacrificed on 3, 5, or 6 dpi, viruses were recovered from lung, brain, heart, pancreas and intestine, among which the highest virus titers were in the lung, brain or heart. Results of virus titration were confirmed by real-time RT-PCR. Genetic and phylogenetic analysis of the HA gene revealed that the isolate belongs to clade 2.3.2.1 similarly to the H5N1 viruses isolated in Vietnam in 2012. The present study demonstrated that this recent HPAI H5N1 virus of clade 2.3.2.1 could replicate efficiently in the systemic organs, including the brain, and cause severe disease with neurological symptoms in domestic ducks. Therefore, this HPAI H5N1 virus seems to retain the neurotrophic feature and has further developed properties of shedding virus from the oropharynx and conjunctiva in addition to the cloaca, potentially posing a higher risk of virus spread through cross-contact and/or environmental transmission. Continued surveillance and diagnostic programs using conjunctival swabs in the field would further verify the apparent reliability of conjunctival samples for the detection of AIV.

  14. Histopathologic Characterization and Shedding Dynamics of Guineafowl (Numida meleagris) Intravenously Infected with a H6N2 Low Pathogenicity Avian Influenza Virus.

    PubMed

    Dimitrov, Kiril M; Zarkov, Ivan S; Dinev, Ivan; Goujgoulova, Gabriela V; Miller, Patti J; Suarez, David L

    2016-05-01

    Guineafowl of different ages were inoculated intravenously with a H6N2 wild waterfowl-origin low pathogenicity avian influenza virus (LPAIV). No clinical disease was observed. The infected birds had atrophy of the spleen, thymus, and cloacal bursa when compared with the noninfected control groups. The central and peripheral lymphoid tissues presented either lymphoproliferative or degenerative lesions that increased in intensity from 14 to 21 days postinoculation (DPI). Lymphoid depletion was present in the bursa, thymic lobes, and spleen T-dependent zone. In contrast, lymphoid proliferation was observed in liver, pancreas, and spleen B-dependent zone. Bronchus associated lymphoid tissue hyperplasia was observed in the lungs of the birds at 14 and 21 DPI. The virus was detected by virus isolation and reverse transcription PCR from both oropharyngeal and cloacal swabs with higher isolation rates from the latter. Most birds from the LPAIV inoculated groups shed virus up to 7 DPI. The virus was infrequently isolated from lung, kidney, liver, bursa, or spleen of infected birds until 14 DPI and from two samples (kidney and spleen, 1-yr-old birds) at 21 DPI. These data indicate that the wild bird-origin LPAIV used in this study caused pantropic infection in guineafowl when inoculated intravenously. PMID:27309068

  15. Oseltamivir-Ribavirin Combination Therapy for Highly Pathogenic H5N1 Influenza Virus Infection in Mice▿

    PubMed Central

    Ilyushina, Natalia A.; Hay, Alan; Yilmaz, Neziha; Boon, Adrianus C. M.; Webster, Robert G.; Govorkova, Elena A.

    2008-01-01

    We studied the effects of a neuraminidase inhibitor (oseltamivir) and an inhibitor of influenza virus polymerases (ribavirin) against two highly pathogenic H5N1 influenza viruses. In vitro, A/Vietnam/1203/04 virus (clade 1) was highly susceptible to oseltamivir carboxylate (50% inhibitory concentration [IC50] = 0.3 nM), whereas A/Turkey/15/06 virus (clade 2.2) had reduced susceptibility (IC50 = 5.5 nM). In vivo, BALB/c mice were treated with oseltamivir (1, 10, 50, or 100 mg/kg of body weight/day), ribavirin (37.5, 55, or 75 mg/kg/day), or the combination of both drugs for 8 days, starting 4 h before virus inoculation. Monotherapy produced a dose-dependent antiviral effect against the two H5N1 viruses in vivo. Three-dimensional analysis of the drug-drug interactions revealed that oseltamivir and ribavirin interacted principally in an additive manner, with several exceptions of marginal synergy or marginal antagonism at some concentrations. The combination of ribavirin at 37.5 mg/kg/day and oseltamivir at 1 mg/kg/day and the combination of ribavirin at 37.5 mg/kg/day and oseltamivir at 10 mg/kg/day were synergistic against A/Vietnam/1203/04 and A/Turkey/15/06 viruses, respectively. These optimal oseltamivir-ribavirin combinations significantly inhibited virus replication in mouse organs, prevented the spread of H5N1 viruses beyond the respiratory tract, and abrogated the cytokine response (P < 0.01). Importantly, we observed clear differences between the efficacies of the drug combinations against two H5N1 viruses: higher doses were required for the protection of mice against A/Turkey/15/06 virus than for the protection of mice against A/Vietnam/1203/04 virus. Our preliminary results suggest that oseltamivir-ribavirin combinations can have a greater or lesser antiviral effect than monotherapy, depending on the H5N1 virus and the concentrations used. PMID:18725448

  16. The Detection of a Low Pathogenicity Avian Influenza Virus Subtype H9 Infection in a Turkey Breeder Flock in the United Kingdom.

    PubMed

    Reid, Scott M; Banks, Jill; Ceeraz, Vanessa; Seekings, Amanda; Howard, Wendy A; Puranik, Anita; Collins, Susan; Manvell, Ruth; Irvine, Richard M; Brown, Ian H

    2016-05-01

    In April 2013, an H9N2 low pathogenicity avian influenza (LPAI) virus was isolated in a turkey breeder farm in Eastern England comprising 4966 birds. Point-of-lay turkey breeding birds had been moved from a rearing site and within 5 days had shown rapid onset of clinical signs of dullness, coughing, and anorexia. Three houses were involved, two contained a total of 4727 turkey hens, and the third housed 239 male turkeys. Around 50% of the hens were affected, whereas the male turkeys demonstrated milder clinical signs. Bird morbidity rose from 10% to 90%, with an increase in mortality in both houses of turkey hens to 17 dead birds in one house and 27 birds in the second house by day 6. The birds were treated with an antibiotic but were not responsive. Postmortem investigation revealed air sacculitis but no infraorbital sinus swellings or sinusitis. Standard samples were collected, and influenza A was detected. H9 virus infection was confirmed in all three houses by detection and subtyping of hemagglutinating agents in embryonated specific-pathogen-free fowls' eggs, which were shown to be viruses of H9N2 subtype using neuraminidase inhibition tests and a suite of real-time reverse transcription PCR assays. LPAI virus pathotype was suggested by cleavage site sequencing, and an intravenous pathogenicity index of 0.00 confirmed that the virus was of low pathogenicity. Therefore, no official disease control measures were required, and despite the high morbidity, birds recovered and were kept in production. Neuraminidase sequence analysis revealed a deletion of 78 nucleotides in the stalk region, suggesting an adaptation of the virus to poultry. Hemagglutinin gene sequences of two of the isolates clustered with a group of H9 viruses containing other contemporary European H9 strains in the Y439/Korean-like group. The closest matches to the two isolates were A/turkey/Netherlands/11015452/11 (H9N2; 97.9-98% nucleotide identity) and A/mallard/Finland/Li13384/10 (H9N2; 97

  17. The Detection of a Low Pathogenicity Avian Influenza Virus Subtype H9 Infection in a Turkey Breeder Flock in the United Kingdom.

    PubMed

    Reid, Scott M; Banks, Jill; Ceeraz, Vanessa; Seekings, Amanda; Howard, Wendy A; Puranik, Anita; Collins, Susan; Manvell, Ruth; Irvine, Richard M; Brown, Ian H

    2016-05-01

    In April 2013, an H9N2 low pathogenicity avian influenza (LPAI) virus was isolated in a turkey breeder farm in Eastern England comprising 4966 birds. Point-of-lay turkey breeding birds had been moved from a rearing site and within 5 days had shown rapid onset of clinical signs of dullness, coughing, and anorexia. Three houses were involved, two contained a total of 4727 turkey hens, and the third housed 239 male turkeys. Around 50% of the hens were affected, whereas the male turkeys demonstrated milder clinical signs. Bird morbidity rose from 10% to 90%, with an increase in mortality in both houses of turkey hens to 17 dead birds in one house and 27 birds in the second house by day 6. The birds were treated with an antibiotic but were not responsive. Postmortem investigation revealed air sacculitis but no infraorbital sinus swellings or sinusitis. Standard samples were collected, and influenza A was detected. H9 virus infection was confirmed in all three houses by detection and subtyping of hemagglutinating agents in embryonated specific-pathogen-free fowls' eggs, which were shown to be viruses of H9N2 subtype using neuraminidase inhibition tests and a suite of real-time reverse transcription PCR assays. LPAI virus pathotype was suggested by cleavage site sequencing, and an intravenous pathogenicity index of 0.00 confirmed that the virus was of low pathogenicity. Therefore, no official disease control measures were required, and despite the high morbidity, birds recovered and were kept in production. Neuraminidase sequence analysis revealed a deletion of 78 nucleotides in the stalk region, suggesting an adaptation of the virus to poultry. Hemagglutinin gene sequences of two of the isolates clustered with a group of H9 viruses containing other contemporary European H9 strains in the Y439/Korean-like group. The closest matches to the two isolates were A/turkey/Netherlands/11015452/11 (H9N2; 97.9-98% nucleotide identity) and A/mallard/Finland/Li13384/10 (H9N2; 97

  18. Viruses infecting reptiles.

    PubMed

    Marschang, Rachel E

    2011-11-01

    A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch's postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions.

  19. Viruses Infecting Reptiles

    PubMed Central

    Marschang, Rachel E.

    2011-01-01

    A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch’s postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions. PMID:22163336

  20. Effect of respiratory syncytial virus (RSV) infection on the adherence of pathogenic bacteria to human epithelial cells

    SciTech Connect

    Faden, H.; Hong, J.J.; Ogra, P.L.

    1986-03-01

    The effect of RSV infection on the adherence of Streptococcus pneumoniae (SP), Haemophilus influenzae (HI) and Staphylococcus aureus (SA) to human epithelial cells was determined. RSV-infected Hep-2 cell cultures at different stages of expression of surface viral antigens and bacteria labeled with /sup 3/H-thymidine were employed to examine the kinetics of bacterial adherence to virus-infected cells. RSV infection did not alter the magnitude of adherence of HI or SA to HEp-2 cells. However, adherence of SP to HEp-2 cells was significantly (P < 0.01) enhanced by prior RSV infection. The degree of adherence was directly related to the amount of viral antigen expressed on the cell surface. The adherence was temperature dependent, with maximal adherence observed at 37/sup 0/C. Heat-inactivation of SP did not alter adherence characteristics. These data suggest that RSV infection increases adherence of SP to the surface of epithelial cells in vitro. Since attachment of bacteria to mucosal surfaces is the first step in many infections, it is suggested that viral infections of epithelial cells render them more susceptible to bacterial adherence. Thus, RSV infection in vivo may predispose children to SP infections, such as in otitis media, by increasing colonization with SP.

  1. Detection of West Nile virus in the tissues of specific pathogen free chickens and serological response to laboratory infection: a comparative study.

    PubMed

    Phipps, L P; Gough, R E; Ceeraz, Vanessa; Cox, W J; Brown, I H

    2007-08-01

    Using an isolate of West Nile virus (WNV) from lineage 1 (Goose/Israel 1998), groups of specific pathogen free chickens were experimentally infected via the subcutaneous or intravenous routes. To evaluate the relative efficiency of detecting the virus in the infected chickens, samples from a range of tissues and organs were examined by virus isolation tests in tissue culture, including Vero, primary chicken embryo liver and fibroblast cells, and polymerase chain reaction (PCR) analyses. Additionally, in order to investigate the serological response of the chickens and produce WNV monospecific antibodies, serum samples were collected from the birds during the trial and analysed for antibodies by virus neutralization (VN) and the plaque-reduction neutralization test (PRNT). No clinical signs or gross pathological changes were seen in any of the inoculated chickens throughout the study. The nested PCR used in the study appeared to be significantly more sensitive at detecting the presence of the virus in both the tissues and the inoculated Vero cell cultures compared with the detection of gross cytopathic changes as observed in infected Vero cell culture. No cytopathic changes were seen in the inoculated avian cell cultures. Following primary inoculation of the chickens there was a weak antibody response 15 days post-inoculation. However, following re-inoculation with inactivated WNV and adjuvant there was a substantial increase in the neutralizing antibody titres when tested 2 weeks later. The results obtained suggested that the PRNT was more sensitive than the conventional VN test. Based on detection of virus and serology there was no evidence of viral transmission to the close contact controls. It can be concluded that the PCR used in this study was more sensitive than virus isolation for the detection of WNV while the PRNT also appeared more sensitive than the conventional VN test.

  2. Human microRNA-24 modulates highly pathogenic avian-origin H5N1 influenza A virus infection in A549 cells by targeting secretory pathway furin.

    PubMed

    Loveday, Emma-Kate; Diederich, Sandra; Pasick, John; Jean, François

    2015-01-01

    A common critical cellular event that many human enveloped viruses share is the requirement for proteolytic cleavage of the viral glycoprotein by furin in the host secretory pathway. For example, the furin-dependent proteolytic activation of highly pathogenic (HP) influenza A (infA) H5 and H7 haemagglutinin precursor (HA0) subtypes is critical for yielding fusion-competent infectious virions. In this study, we hypothesized that viral hijacking of the furin pathway by HP infA viruses to permit cleavage of HA0 could represent a novel molecular mechanism controlling the dynamic production of fusion-competent infectious virus particles during the viral life cycle. We explored the biological role of a newly identified furin-directed human microRNA, miR-24, in this process as a potential post-transcriptional regulator of the furin-mediated activation of HA0 and production of fusion-competent virions in the host secretory pathway. We report that miR-24 and furin are differentially expressed in human A549 cells infected with HP avian-origin infA H5N1. Using miR-24 mimics, we demonstrated a robust decrease in both furin mRNA levels and intracellular furin activity in A549 cells. Importantly, pretreatment of A549 cells with miR-24 mimicked these results: a robust decrease of H5N1 infectious virions and a complete block of H5N1 virus spread that was not observed in A549 cells infected with low-pathogenicity swine-origin infA H1N1 virus. Our results suggest that viral-specific downregulation of furin-directed microRNAs such as miR-24 during the life cycle of HP infA viruses may represent a novel regulatory mechanism that governs furin-mediated proteolytic activation of HA0 glycoproteins and production of infectious virions.

  3. Reduced experimental infectivity and transmissibility of intercontinental H5 (H5N8 and H5N2) compared to Eurasian H5N1 highly pathogenic avian influenza viruses for chickens, turkeys, and Japanese quail

    Technology Transfer Automated Retrieval System (TEKTRAN)

    H5N1 high pathogenicity avian influenza (HPAI) virus (HPAIV) emerged in 1996 in Guangdong China and has since spread to infect and cause deaths in wild birds, poultry and humans in over 63 countries in Asia, Europe and Africa; and more recently a reassortant H5N8 clade 2.3.4.4 HPAI virus has spread ...

  4. Pathogenic human viruses in coastal waters

    USGS Publications Warehouse

    Griffin, Dale W.; Donaldson, Kim A.; Paul, J.H.; Rose, Joan B.

    2003-01-01

    This review addresses both historical and recent investigations into viral contamination of marine waters. With the relatively recent emergence of molecular biology-based assays, a number of investigations have shown that pathogenic viruses are prevalent in marine waters being impacted by sewage. Research has shown that this group of fecal-oral viral pathogens (enteroviruses, hepatitis A viruses, Norwalk viruses, reoviruses, adenoviruses, rotaviruses, etc.) can cause a broad range of asymptomatic to severe gastrointestinal, respiratory, and eye, nose, ear, and skin infections in people exposed through recreational use of the water. The viruses and the nucleic acid signature survive for an extended period in the marine environment. One of the primary concerns of public health officials is the relationship between the presence of pathogens and the recreational risk to human health in polluted marine environments. While a number of studies have attempted to address this issue, the relationship is still poorly understood. A contributing factor to our lack of progress in the field has been the lack of sensitive methods to detect the broad range of both bacterial and viral pathogens. The application of new and advanced molecular methods will continue to contribute to our current state of knowledge in this emerging and

  5. Pathogenic Human Viruses in Coastal Waters

    PubMed Central

    Griffin, Dale W.; Donaldson, Kim A.; Paul, John H.; Rose, Joan B.

    2003-01-01

    This review addresses both historical and recent investigations into viral contamination of marine waters. With the relatively recent emergence of molecular biology-based assays, a number of investigations have shown that pathogenic viruses are prevalent in marine waters being impacted by sewage. Research has shown that this group of fecal-oral viral pathogens (enteroviruses, hepatitis A viruses, Norwalk viruses, reoviruses, adenoviruses, rotaviruses, etc.) can cause a broad range of asymptomatic to severe gastrointestinal, respiratory, and eye, nose, ear, and skin infections in people exposed through recreational use of the water. The viruses and the nucleic acid signature survive for an extended period in the marine environment. One of the primary concerns of public health officials is the relationship between the presence of pathogens and the recreational risk to human health in polluted marine environments. While a number of studies have attempted to address this issue, the relationship is still poorly understood. A contributing factor to our lack of progress in the field has been the lack of sensitive methods to detect the broad range of both bacterial and viral pathogens. The application of new and advanced molecular methods will continue to contribute to our current state of knowledge in this emerging and important field. PMID:12525429

  6. Morpholino oligomers targeting the PB1 and NP genes enhance the survival of mice infected with highly pathogenic influenza A H7N7 virus.

    PubMed

    Gabriel, Gülsah; Nordmann, Alexandra; Stein, David A; Iversen, Patrick L; Klenk, Hans-Dieter

    2008-04-01

    Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are single-stranded nucleic acid-analogue antisense agents that enter cells readily and can reduce gene expression by steric blocking of complementary RNA (cRNA) sequences. Here, we tested a panel of PPMO designed to target conserved sequences in the RNA genome segments encoding polymerase subunits of a highly pathogenic mouse-adapted influenza A virus (SC35M; H7N7). Three PPMO, targeting the translation start site region of PB1 or NP mRNA or the 3'-terminal region of NP viral RNA (vRNA), potently inhibited virus replication in MDCK cells. Primer extension assays showed that treatment with any of the effective PPMO led to markedly reduced levels of mRNA, cRNA and vRNA. Initially, the potential toxicity of a range of intranasally administered PPMO doses was evaluated, by measuring their effect on body weight of uninfected mice. Subsequently, a non-toxic dosing regimen was used to investigate the effect of various PPMO on SC35M infection in a mouse model. Mice administered intranasal treatment of PPMO targeting the PB1-AUG region or NP vRNA, at 3 mug per dose, given once 3 h before and once 2 days after intranasal infection with 10xLD(50) of SC35M, showed a 2 log(10) reduction of viral titre in the lungs and 50 % survival for the 16 day duration of the experiment, whereas the NP-AUG-targeted PPMO treatment resulted in 30 % survival of an otherwise lethal infection. These data suggest that PPMO provide a useful reagent to investigate influenza virus molecular biology and may constitute a therapeutic strategy against highly pathogenic influenza viruses.

  7. Bagaza virus is pathogenic and transmitted by direct contact in experimentally infected partridges, but is not infectious in house sparrows and adult mice.

    PubMed

    Llorente, Francisco; Pérez-Ramírez, Elisa; Fernández-Pinero, Jovita; Elizalde, Maia; Figuerola, Jordi; Soriguer, Ramón C; Jiménez-Clavero, Miguel Ángel

    2015-01-01

    Bagaza virus (BAGV) is a mosquito-borne flavivirus belonging to the Ntaya serocomplex. In 2010, a disease outbreak was reported in Cádiz (Southern Spain) affecting game birds (red-legged partridges and common pheasants). In this work, red-legged partridges were inoculated experimentally with infectious BAGV isolated from this outbreak in order to make a complete clinical and analytical assessment of the disease caused by the pathogen in this species. Viral load (by real-time RT-PCR) in blood, oral and cloacal swabs, and feathers, and neutralizing antibody titres (by VNT) were measured. In order to determine direct contact transmission, non-inoculated partridges were caged together with the inoculated ones. To assess infectiousness in other species, house sparrows and mice were also inoculated with the virus. All the inoculated partridges were clinically affected, and 30% of them died. All the infected individuals lost weight, with larger losses being recorded in females. Conversely, no mortality or disease symptoms were observed in the sparrows or mice. Remarkably, all the contact partridges acquired the infection by direct (non-vectored) transmission. This study confirms that the red-legged partridge is a susceptible host for BAGV infection, and that this pathogen is transmitted by direct contact. Long-lasting viral loads detected in calami of immature feathers demonstrate that feather sampling could be a useful strategy in active surveillance programs for early detection of BAGV. PMID:26338714

  8. Bagaza virus is pathogenic and transmitted by direct contact in experimentally infected partridges, but is not infectious in house sparrows and adult mice.

    PubMed

    Llorente, Francisco; Pérez-Ramírez, Elisa; Fernández-Pinero, Jovita; Elizalde, Maia; Figuerola, Jordi; Soriguer, Ramón C; Jiménez-Clavero, Miguel Ángel

    2015-01-01

    Bagaza virus (BAGV) is a mosquito-borne flavivirus belonging to the Ntaya serocomplex. In 2010, a disease outbreak was reported in Cádiz (Southern Spain) affecting game birds (red-legged partridges and common pheasants). In this work, red-legged partridges were inoculated experimentally with infectious BAGV isolated from this outbreak in order to make a complete clinical and analytical assessment of the disease caused by the pathogen in this species. Viral load (by real-time RT-PCR) in blood, oral and cloacal swabs, and feathers, and neutralizing antibody titres (by VNT) were measured. In order to determine direct contact transmission, non-inoculated partridges were caged together with the inoculated ones. To assess infectiousness in other species, house sparrows and mice were also inoculated with the virus. All the inoculated partridges were clinically affected, and 30% of them died. All the infected individuals lost weight, with larger losses being recorded in females. Conversely, no mortality or disease symptoms were observed in the sparrows or mice. Remarkably, all the contact partridges acquired the infection by direct (non-vectored) transmission. This study confirms that the red-legged partridge is a susceptible host for BAGV infection, and that this pathogen is transmitted by direct contact. Long-lasting viral loads detected in calami of immature feathers demonstrate that feather sampling could be a useful strategy in active surveillance programs for early detection of BAGV.

  9. Effect of porcine circovirus type 2a or 2b on infection kinetics and pathogenicity of two genetically divergent strains of porcine reproductive and respiratory syndrome virus in the conventional pig model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to characterize the infection dynamics and pathogenicity of two heterologous type 2 porcine reproductive and respiratory syndrome virus (PRRSV) isolates in a conventional pig model under the influence of concurrent porcine circovirus (PCV) subtype 2a or 2b infection. ...

  10. A comparative evaluation of feathers, oropharyngeal swabs, and cloacal swabs for the detection of H5N1 highly pathogenic avian influenza virus infection in experimentally infected chickens and ducks.

    PubMed

    Nuradji, Harimurti; Bingham, John; Lowther, Sue; Wibawa, Hendra; Colling, Axel; Long, Ngo Thanh; Meers, Joanne

    2015-11-01

    Oropharyngeal and cloacal swabs have been widely used for the detection of H5N1 highly pathogenic avian Influenza A virus (HPAI virus) in birds. Previous studies have shown that the feather calamus is a site of H5N1 virus replication and therefore has potential for diagnosis of avian influenza. However, studies characterizing the value of feathers for this purpose are not available, to our knowledge; herein we present a study investigating feathers for detection of H5N1 virus. Ducks and chickens were experimentally infected with H5N1 HPAI virus belonging to 1 of 3 clades (Indonesian clades 2.1.1 and 2.1.3, Vietnamese clade 1). Different types of feathers and oropharyngeal and cloacal swab samples were compared by virus isolation. In chickens, virus was detected from all sample types: oral and cloacal swabs, and immature pectorosternal, flight, and tail feathers. During clinical disease, the viral titers were higher in feathers than swabs. In ducks, the proportion of virus-positive samples was variable depending on viral strain and time from challenge; cloacal swabs and mature pectorosternal feathers were clearly inferior to oral swabs and immature pectorosternal, tail, and flight feathers. In ducks infected with Indonesian strains, in which most birds did not develop clinical signs, all sampling methods gave intermittent positive results; 3-23% of immature pectorosternal feathers were positive during the acute infection period; oropharyngeal swabs had slightly higher positivity during early infection, while feathers performed better during late infection. Our results indicate that immature feathers are an alternative sample for the diagnosis of HPAI in chickens and ducks.

  11. Influenza Virus Infection of Marine Mammals.

    PubMed

    Fereidouni, Sasan; Munoz, Olga; Von Dobschuetz, Sophie; De Nardi, Marco

    2016-03-01

    Interspecies transmission may play a key role in the evolution and ecology of influenza A viruses. The importance of marine mammals as hosts or carriers of potential zoonotic pathogens such as highly pathogenic H5 and H7 influenza viruses is not well understood. The fact that influenza viruses are some of the few zoonotic pathogens known to have caused infection in marine mammals, evidence for direct transmission of influenza A virus H7N7 subtype from seals to man, transmission of pandemic H1N1 influenza viruses to seals and also limited evidence for long-term persistence of influenza B viruses in seal populations without significant genetic change, makes monitoring of influenza viruses in marine mammal populations worth being performed. In addition, such monitoring studies could be a great tool to better understand the ecology of influenza viruses in nature. PMID:25231137

  12. Experimental infection of a North American raptor, American kestrel (Falco sparverius), with highly pathogenic avian influenza virus (H5N1)

    USGS Publications Warehouse

    Hall, J.S.; Ip, H.S.; Franson, J.C.; Meteyer, C.; Nashold, S.; Teslaa, J.L.; French, J.; Redig, P.; Brand, C.

    2009-01-01

    Several species of wild raptors have been found in Eurasia infected with highly pathogenic avian influenza virus (HPAIV) subtype H5N1. Should HPAIV (H5N1) reach North America in migratory birds, species of raptors are at risk not only from environmental exposure, but also from consuming infected birds and carcasses. In this study we used American kestrels as a representative species of a North American raptor to examine the effects of HPAIV (H5N1) infection in terms of dose response, viral shedding, pathology, and survival. Our data showed that kestrels are highly susceptible to HPAIV (H5N1). All birds typically died or were euthanized due to severe neurologic disease within 4-5 days of inoculation and shed significant amounts of virus both orally and cloacally, regardless of dose administered. The most consistent microscopic lesions were necrosis in the brain and pancreas. This is the first experimental study of HPAIV infection in a North American raptor and highlights the potential risks to birds of prey if HPAIV (H5N1) is introduced into North America.

  13. Risk Reduction Modeling of High Pathogenicity Avian Influenza Virus Titers in Nonpasteurized Liquid Egg Obtained from Infected but Undetected Chicken Flocks.

    PubMed

    Weaver, J Todd; Malladi, Sasidhar; Spackman, Erica; Swayne, David E

    2015-11-01

    Control of highly pathogenic avian influenza (HPAI) outbreaks in poultry has traditionally involved the establishment of disease containment zones, where poultry products are only permitted to move from within a zone under permit. Nonpasteurized liquid egg (NPLE) is one such commodity for which movements may be permitted, considering inactivation of HPAI virus via pasteurization. Active surveillance testing at the flock level, using targeted matrix gene real-time reversed transcriptase-polymerase chain reaction testing (RRT-PCR) has been incorporated into HPAI emergency response plans as the primary on-farm diagnostic test procedure to detect HPAI in poultry and is considered to be a key risk mitigation measure. To inform decisions regarding the potential movement of NPLE to a pasteurization facility, average HPAI virus concentrations in NPLE produced from a HPAI virus infected, but undetected, commercial table-egg-layer flock were estimated for three HPAI virus strains using quantitative simulation models. Pasteurization under newly proposed international design standards (5 log10 reduction) is predicted to inactivate HPAI virus in NPLE to a very low concentration of less than 1 embryo infectious dose (EID)50 /mL, considering the predicted virus titers in NPLE from a table-egg flock under active surveillance. Dilution of HPAI virus from contaminated eggs in eggs from the same flock, and in a 40,000 lb tanker-truck load of NPLE containing eggs from disease-free flocks was also considered. Risk assessment can be useful in the evaluation of commodity-specific risk mitigation measures to facilitate safe trade in animal products from countries experiencing outbreaks of highly transmissible animal diseases.

  14. Combinations of Oseltamivir and T-705 Extend the Treatment Window for Highly Pathogenic Influenza A(H5N1) Virus Infection in Mice

    PubMed Central

    Marathe, Bindumadhav M.; Wong, Sook-San; Vogel, Peter; Garcia-Alcalde, Fernando; Webster, Robert G.; Webby, Richard J.; Najera, Isabel; Govorkova, Elena A.

    2016-01-01

    Current anti-influenza therapy depends on administering drugs soon after infection, which is often impractical. We assessed whether combinations of oseltamivir (a neuraminidase inhibitor) and T-705 (a nonspecific inhibitor of viral polymerases) could extend the window for treating lethal infection with highly pathogenic A(H5N1) influenza virus in mice. Combination therapy protected 100% of mice, even when delayed until 96 h postinoculation. Compared to animals receiving monotherapy, mice receiving combination therapy had reduced viral loads and restricted viral spread in lung tissues, limited lung damage, and decreased inflammatory cytokine production. Next-generation sequencing showed that virus populations in T-705–treated mice had greater genetic variability, with more frequent transversion events, than did populations in control and oseltamivir-treated mice, but no substitutions associated with resistance to oseltamivir or T-705 were detected. Thus, combination therapy extended the treatment window for A(H5N1) influenza infection in mice and should be considered for evaluation in a clinical setting. PMID:27221530

  15. Combinations of Oseltamivir and T-705 Extend the Treatment Window for Highly Pathogenic Influenza A(H5N1) Virus Infection in Mice.

    PubMed

    Marathe, Bindumadhav M; Wong, Sook-San; Vogel, Peter; Garcia-Alcalde, Fernando; Webster, Robert G; Webby, Richard J; Najera, Isabel; Govorkova, Elena A

    2016-01-01

    Current anti-influenza therapy depends on administering drugs soon after infection, which is often impractical. We assessed whether combinations of oseltamivir (a neuraminidase inhibitor) and T-705 (a nonspecific inhibitor of viral polymerases) could extend the window for treating lethal infection with highly pathogenic A(H5N1) influenza virus in mice. Combination therapy protected 100% of mice, even when delayed until 96 h postinoculation. Compared to animals receiving monotherapy, mice receiving combination therapy had reduced viral loads and restricted viral spread in lung tissues, limited lung damage, and decreased inflammatory cytokine production. Next-generation sequencing showed that virus populations in T-705-treated mice had greater genetic variability, with more frequent transversion events, than did populations in control and oseltamivir-treated mice, but no substitutions associated with resistance to oseltamivir or T-705 were detected. Thus, combination therapy extended the treatment window for A(H5N1) influenza infection in mice and should be considered for evaluation in a clinical setting. PMID:27221530

  16. Impact of vaccination on infection with Vietnam H5N1 high pathogenicity avian influenza virus in hens and the eggs they lay.

    PubMed

    Bertran, Kateri; Moresco, Kira; Swayne, David E

    2015-03-10

    High pathogenicity avian influenza virus (HPAIV) infections in chickens negatively impact egg production and cause egg contamination. Previously, vaccination maintained egg production and reduced egg contamination when challenged with a North American H5N2 HPAIV. However, Asian H5N1 HPAIV infection has some characteristics of increased pathogenicity compared to other H5 HPAIV such as more rapid drop and complete cessation in egg production. Sham (vaccinated at 25 and 28 weeks of age), inactivated H5N1 Once (1X-H5-Vax; vaccinated at 28 weeks of age only) and inactivated H5N1 Twice (2X-H5-Vax; vaccinated at 25 and 28 weeks of age) vaccinated adult White Leghorn hens were challenged intranasally at 31 weeks of age with 6.1 log10 mean embryo infectious doses (EID50) of clade 2.3.2.1a H5N1 HPAIV (A/chicken/Vietnam/NCVD-675/2011) which was homologous to the inactivated vaccine. Sham-vaccinated layers experienced 100% mortality within 3 days post-challenge; laid soft and thin-shelled eggs; had recovery of virus from oral swabs and in 53% of the eggs from eggshell surface (35%), yolk (24%), and albumin (41%); and had very high titers of virus (average 7.91 log10 EID50/g) in all segments of the oviduct and ovary. By comparison, 1X- and 2X-H5-Vax challenged hens survived infection, laid similar number of eggs pre- and post-challenge, all eggs had normal egg shell quality, and had significantly fewer contaminated eggs with reduced virus quantity. The 2X-H5-Vax hens had significantly higher HI titers by the day of challenge (304 GMT) and at termination (512 GMT) than 1X-H5-Vax hens (45 GMT and 128 GMT). The current study demonstrated that AIV infections caused by clade 2.3.2.1a H5N1 variants can be effectively controlled by either double or single homologous vaccination. PMID:25657093

  17. Virus Infections in the Nervous System

    PubMed Central

    Koyuncu, Orkide O.; Hogue, Ian B.; Enquist, Lynn W.

    2013-01-01

    Virus infections usually begin in peripheral tissues and can invade the mammalian nervous system (NS), spreading into the peripheral (PNS) and more rarely the central nervous systems (CNS). The CNS is protected from most virus infections by effective immune responses and multi-layer barriers. However, some viruses enter the NS with high efficiency via the bloodstream or by directly infecting nerves that innervate peripheral tissues, resulting in debilitating direct and immune-mediated pathology. Most viruses in the NS are opportunistic or accidental pathogens, but a few, most notably the alpha herpesviruses and rabies virus, have evolved to enter the NS efficiently and exploit neuronal cell biology. Remarkably, the alpha herpesviruses can establish quiescent infections in the PNS, with rare but often fatal CNS pathology. Here we review how viruses gain access to and spread in the well-protected CNS, with particular emphasis on alpha herpesviruses, which establish and maintain persistent NS infections. PMID:23601101

  18. Local interactions select for lower pathogen infectivity.

    PubMed

    Boots, Michael; Mealor, Michael

    2007-03-01

    Theory suggests that the current rapid increase in connectivity and consequential changes in the structure of human, agricultural, and wildlife populations may select for parasite strains with higher infectivity. We carried out a test of this spatial theory by experimentally altering individual host movement rates in a model host/pathogen system by altering the viscosity of their environment. In our microevolutionary selection experiments, the infectivity of the virus was, as predicted by the theory, reduced in the most viscous populations. We therefore provide empirical support for the theory that population structure affects the evolution of infectious organisms.

  19. [ZIKA--VIRUS INFECTION].

    PubMed

    Velev, V

    2016-01-01

    This review summarizes the knowledge of the scientific community for Zika-virus infection. It became popular because of severe congenital damage causes of CNS in newborns whose mothers are infected during pregnancy, as well as the risk of pandemic distribution. Discusses the peculiarities of the biology and ecology of vectors--blood-sucking mosquitoes Aedes; stages in the spread of infection and practical problems which caused during pregnancy. Attention is paid to the recommendations that allow leading national and international medical organizations to deal with the threat Zika-virus infection. PMID:27509655

  20. [ZIKA--VIRUS INFECTION].

    PubMed

    Velev, V

    2016-01-01

    This review summarizes the knowledge of the scientific community for Zika-virus infection. It became popular because of severe congenital damage causes of CNS in newborns whose mothers are infected during pregnancy, as well as the risk of pandemic distribution. Discusses the peculiarities of the biology and ecology of vectors--blood-sucking mosquitoes Aedes; stages in the spread of infection and practical problems which caused during pregnancy. Attention is paid to the recommendations that allow leading national and international medical organizations to deal with the threat Zika-virus infection.

  1. Outbreak of H5N2 highly pathogenic avian Influenza A virus infection in two commercial layer facilities: lesions and viral antigen distribution.

    PubMed

    Arruda, Paulo H E; Stevenson, Gregory W; Killian, Mary L; Burrough, Eric R; Gauger, Phillip C; Harmon, Karen M; Magstadt, Drew R; Yoon, Kyoung-Jin; Zhang, Jianqiang; Madson, Darin M; Piñeyro, Pablo; Derscheid, Rachel J; Schwartz, Kent J; Cooper, Vickie L; Halbur, Patrick G; Main, Rodger G; Sato, Yuko; Arruda, Bailey L

    2016-09-01

    The largest outbreak of highly pathogenic avian Influenza A virus (HPAIV) infection in U.S. history began in December 2014 resulting in the euthanasia of millions of birds and collateral economic consequences to the U.S. poultry industry. We describe 2 cases of H5N2 HPAIV infection in laying hens in Iowa. Following a sharp increase in mortality with minimal clinical signs, 15 dead birds, from 2 unrelated farms, were submitted to the Iowa State University Veterinary Diagnostic Laboratory. Common lesions included diffuse edema and multifocal hemorrhage of the comb, catarrhal exudate in the oropharynx, and multifocal tracheal hemorrhage. Less common lesions included epicardial petechiae, splenic hemorrhage, and pancreatic necrosis. Influenza A virus nucleoprotein was detected by immunohistochemistry in multiple cell types including ependymal cells, the choroid plexus, neurons, respiratory epithelium and macrophages in the lung, cardiac myocytes, endothelial cells, necrotic foci in the spleen, Kupffer cells in the liver, and necrotic acinar cells in the pancreas. Real-time polymerase chain reaction and sequencing confirmed H5N2 HPAIV with molecular characteristics similar to other contemporary U.S. H5N2 HPAIVs in both cases. PMID:27423731

  2. Acute otitis media and respiratory virus infections.

    PubMed

    Ruuskanen, O; Arola, M; Putto-Laurila, A; Mertsola, J; Meurman, O; Viljanen, M K; Halonen, P

    1989-02-01

    We studied the association of acute otitis media with different respiratory virus infections in a pediatric department on the basis of epidemics between 1980 and 1985. Altogether 4524 cases of acute otitis media were diagnosed. The diagnosis was confirmed by tympanocentesis in 3332 ears. Respiratory virus infection was diagnosed during the same period in 989 patients by detecting viral antigen in nasopharyngeal mucus. There was a significant correlation between acute otitis media and respiratory virus epidemics, especially respiratory syncytial virus epidemics. There was no significant correlation between outbreaks of other respiratory viruses and acute otitis media. Acute otitis media was diagnosed in 57% of respiratory syncytial virus, 35% of influenza A virus, 33% of parainfluenza type 3 virus, 30% of adenovirus, 28% of parainfluenza type 1 virus, 18% of influenza B virus and 10% of parainfluenza type 2 virus infections. These observations show a clear association of respiratory virus infections with acute otitis media. In this study on hospitalized children Haemophilus influenzae strains were the most common bacteriologic pathogens in middle ear fluid, occurring in 19% of cases. Streptococcus pneumoniae was present in 16% and Branhamella catarrhalis in 7% of cases. There was no association between specific viruses and bacteria observed in this study.

  3. Advances in Diagnosis of Respiratory Virus Infections

    PubMed Central

    Loeffelholz, Michael; Chonmaitree, Tasnee

    2010-01-01

    The diagnosis of respiratory virus infections has evolved substantially in recent years, with the emergence of new pathogens and the development of novel detection methods. While recent advances have improved the sensitivity and turn-around time of diagnostic tests for respiratory viruses, they have also raised important issues such as cost, and the clinical significance of detecting multiple viruses in a single specimen by molecular methods. This article reviews recent advances in specimen collection and detection methods for diagnosis of respiratory virus infections, and discusses the performance characteristics and limitations of these methods. PMID:20981303

  4. Visualizing influenza virus infection in living mice

    PubMed Central

    Pan, Weiqi; Dong, Zhenyuan; Li, Feng; Meng, Weixu; Feng, Liqiang; Niu, Xuefeng; Li, Chufang; Luo, Qinfang; Li, Zhengfeng; Sun, Caijun; Chen, Ling

    2013-01-01

    Preventing and treating influenza virus infection remain a challenge because of incomplete understanding of the host–pathogen interactions, limited therapeutics and lack of a universal vaccine. So far, methods for monitoring the course of infection with influenza virus in real time in living animals are lacking. Here we report the visualization of influenza viral infection in living mice using an engineered replication-competent influenza A virus carrying luciferase reporter gene. After intranasal inoculation, bioluminescence can be detected in the chest and nasopharyngeal passage of living mice. The intensity of bioluminescence in the chest correlates with the dosage of infection and the viral load in the lung. Bioluminescence in the chest of infected mice diminishes on antiviral treatment. This work provides a novel approach that enables real-time study of influenza virus infection and effects of antiviral therapeutics in living animals. PMID:24022374

  5. Persistence of Highly Pathogenic Avian Influenza Viruses in Natural Ecosystems

    PubMed Central

    Feare, Chris J.; Renaud, François; Thomas, Frédéric; Gauthier-Clerc, Michel

    2010-01-01

    Understanding of ecologic factors favoring emergence and maintenance of highly pathogenic avian influenza (HPAI) viruses is limited. Although low pathogenic avian influenza viruses persist and evolve in wild populations, HPAI viruses evolve in domestic birds and cause economically serious epizootics that only occasionally infect wild populations. We propose that evolutionary ecology considerations can explain this apparent paradox. Host structure and transmission possibilities differ considerably between wild and domestic birds and are likely to be major determinants of virulence. Because viral fitness is highly dependent on host survival and dispersal in nature, virulent forms are unlikely to persist in wild populations if they kill hosts quickly or affect predation risk or migratory performance. Interhost transmission in water has evolved in low pathogenic influenza viruses in wild waterfowl populations. However, oropharyngeal shedding and transmission by aerosols appear more efficient for HPAI viruses among domestic birds. PMID:20587174

  6. Akabane virus infection.

    PubMed

    Kirkland, P D

    2015-08-01

    Akabane virus is a Culicoides-borne orthobunyavirus that is teratogenic to the fetus of cattle and small ruminant species. Depending upon the stage of gestation atwhich infection occurs, and the length of gestation of the mammalian host, a range of congenital defects may be observed. The developing central nervous system is usually the most severely affected, with hydranencephaly and arthrogryposis most frequently observed. Less commonly, some strains of Akabane virus can cause encephalitis in the neonate or, rarely, adult cattle. Akabane viruses are known to be widespread in temperate and tropical regions of Australia, Southeast Asia, the Middle East and some African countries. Disease is infrequently observed in regions where this virus is endemic and the presence of the virus remains unrecognised in the absence of serological surveillance. In some Asian countries, vaccines are used to minimise the occurrence of disease. PMID:26601444

  7. Highly Pathogenic Avian Influenza H5N8 Clade 2.3.4.4 Virus: Equivocal Pathogenicity and Implications for Surveillance Following Natural Infection in Breeder Ducks in the United Kingdom.

    PubMed

    Núñez, A; Brookes, S M; Reid, S M; Garcia-Rueda, C; Hicks, D J; Seekings, J M; Spencer, Y I; Brown, I H

    2016-02-01

    Since early 2014, several outbreaks involving novel reassortant highly pathogenic avian influenza (HPAI) A(H5N8) viruses have been detected in poultry and wild bird species in Asia, Europe and North America. These viruses have been detected in apparently healthy and dead wild migratory birds, as well as in domestic chickens, turkeys, geese and ducks. In this study, we describe the pathology of an outbreak of H5N8 HPAIV in breeder ducks in the UK. A holding with approximately 6000 breeder ducks, aged approximately 60 weeks, showed a gradual reduction in egg production and increased mortality over a 7-day period. Post-mortem examination revealed frequent fibrinous peritonitis, with severely haemorrhagic ovarian follicles and occasional splenic and pancreatic necrosis and high incidence of mycotic granulomas in the air sacs and lung. Low-to-moderate levels of HPAI H5N8 virus were detected mainly in respiratory and digestive tract, with minor involvement of other organs. Although histopathological examination confirmed the gross pathology findings, intralesional viral antigen detection by immunohistochemistry was not observed. Immunolabelled cells were rarely only present in inflamed air sacs and serosa, usually superficial to granulomatous inflammation. Abundant bacterial microcolonies were observed in haemorrhagic ovaries and oviduct. The limited viral tissue distribution and presence of inter-current fungal and bacterial infections suggest a minor role for HPAIV H5N8 in clinical disease in layer ducks. PMID:26519234

  8. Detecting the emergence of novel, zoonotic viruses pathogenic to humans

    PubMed Central

    2015-01-01

    RNA viruses, with their high potential for mutation and epidemic spread, are the most common class of pathogens found as new causes of human illness. Despite great advances made in diagnostic technology since the 1950s, the annual rate at which novel virulent viruses have been found has remained at 2–3. Most emerging viruses are zoonoses; they have jumped from mammal or bird hosts to humans. An analysis of virus discovery indicates that the small number of novel viruses discovered annually is an artifact of inadequate surveillance in tropical and subtropical countries, where even established endemic pathogens are often misdiagnosed. Many of the emerging viruses of the future are already infecting humans but remain to be uncovered by a strategy of disease surveillance in selected populations. PMID:25416679

  9. Schmallenberg virus infection.

    PubMed

    Wernike, K; Elbers, A; Beer, M

    2015-08-01

    Since Schmallenberg virus, an orthobunyavirus of the Simbu serogroup, was identified near the German-Dutch border for the first time in late 2011 it has spread extremely quickly and caused a large epidemic in European livestock. The virus, which is transmitted by Culicoides biting midges, infects domestic and wild ruminants. Adult animals show only mild clinical symptoms or none at all, whereas an infection during a critical period of gestation can lead to abortion, stillbirth or the birth of severely malformed offspring. The impact of the disease is usually greater in sheep than in cattle. Vaccination could be an important aspect of disease control. PMID:26601441

  10. Zika Virus Infection and Microcephaly.

    PubMed

    Millichap, J Gordon

    2016-01-01

    A Task Force established by the Brazil Ministry of Health investigated the possible association of microcephaly with Zika virus infection during pregnancy and a registry for microcephaly cases among women suspected to have had Zika virus infection during pregnancy.

  11. Integrated Omics Analysis of Pathogenic Host Responses during Pandemic H1N1 Influenza Virus Infection: The Crucial Role of Lipid Metabolism.

    PubMed

    Tisoncik-Go, Jennifer; Gasper, David J; Kyle, Jennifer E; Eisfeld, Amie J; Selinger, Christian; Hatta, Masato; Morrison, Juliet; Korth, Marcus J; Zink, Erika M; Kim, Young-Mo; Schepmoes, Athena A; Nicora, Carrie D; Purvine, Samuel O; Weitz, Karl K; Peng, Xinxia; Green, Richard R; Tilton, Susan C; Webb-Robertson, Bobbie-Jo; Waters, Katrina M; Metz, Thomas O; Smith, Richard D; Kawaoka, Yoshihiro; Suresh, M; Josset, Laurence; Katze, Michael G

    2016-02-10

    Pandemic influenza viruses modulate proinflammatory responses that can lead to immunopathogenesis. We present an extensive and systematic profiling of lipids, metabolites, and proteins in respiratory compartments of ferrets infected with either 1918 or 2009 human pandemic H1N1 influenza viruses. Integrative analysis of high-throughput omics data with virologic and histopathologic data uncovered relationships between host responses and phenotypic outcomes of viral infection. Proinflammatory lipid precursors in the trachea following 1918 infection correlated with severe tracheal lesions. Using an algorithm to infer cell quantity changes from gene expression data, we found enrichment of distinct T cell subpopulations in the trachea. There was also a predicted increase in inflammatory monocytes in the lung of 1918 virus-infected animals that was sustained throughout infection. This study presents a unique resource to the influenza research community and demonstrates the utility of an integrative systems approach for characterization of lipid metabolism alterations underlying respiratory responses to viruses.

  12. Emergence of highly pathogenic virus during selective chicken passage of the prototype mildly pathogenic chicken/Pennsylvania/83 (H5N2) influenza virus.

    PubMed

    Brugh, M; Perdue, M L

    1991-01-01

    The prototype mildly pathogenic A/chicken/Pennsylvania/21525/83 (H5N2) avian influenza virus, which was isolated more than 5 months before the emergence of highly pathogenic virus in the major 1983 Pennsylvania outbreak, was examined for the presence of minority subpopulations of highly pathogenic virus. Selective serial passage of the parental mildly pathogenic virus in leghorn hens did not lead to recovery of highly pathogenic virus. However, several highly pathogenic reisolates were recovered from hens inoculated with either of two mildly pathogenic virus clones selected for their ability to efficiently produce plaques in trypsin-free chicken embryo fibroblasts. Unlike the parental virus, these reisolates caused high mortality in chickens and produced postmortem lesions typical of highly pathogenic avian influenza. Electrophoretic mobilities of the hemagglutinin glycoproteins of the highly pathogenic derivatives resembled those of the prototype highly pathogenic A/chicken/Pennsylvania/1370/83 (H5N2) virus isolated in October 1983. These results suggest that unrecognized subpopulations of highly pathogenic virus may have infected Pennsylvania chickens for several months before emerging as the clinically manifest component of the virus population.

  13. Pathogenicity of two Egyptian H5N1 highly pathogenic avian influenza viruses in domestic ducks.

    PubMed

    Wasilenko, J L; Arafa, A M; Selim, A A; Hassan, M K; Aly, M M; Ali, A; Nassif, S; Elebiary, E; Balish, A; Klimov, A; Suarez, D L; Swayne, D E; Pantin-Jackwood, M J

    2011-01-01

    Domestic ducks have been implicated in the dissemination and evolution of H5N1 highly pathogenic avian influenza (HPAI) viruses. In this study, two H5N1 HPAI viruses belonging to clade 2.2.1 isolated in Egypt in 2007 and 2008 were analyzed for their pathogenicity in domestic Pekin ducks. Both viruses produced clinical signs and mortality, but the 2008 virus was more virulent, inducing early onset of neurological signs and killing all ducks with a mean death time (MDT) of 4.1 days. The 2007 virus killed 3/8 ducks with a MDT of 7 days. Full-genome sequencing and phylogenetic analysis were used to examine differences in the virus genes that might explain the differences observed in pathogenicity. The genomes differed in 49 amino acids, with most of the differences found in the hemagglutinin protein. This increase in pathogenicity in ducks observed with certain H5N1 HPAI viruses has implications for the control of the disease, since vaccinated ducks infected with highly virulent strains shed viruses for longer periods of time, perpetuating the virus in the environment and increasing the possibility of transmission to susceptible birds.

  14. Accumulation of CD11b⁺Gr-1⁺ cells in the lung, blood and bone marrow of mice infected with highly pathogenic H5N1 and H1N1 influenza viruses.

    PubMed

    Long, James P; Kotur, Mark S; Stark, Gregory V; Warren, Richard L; Kasoji, Manjula; Craft, Jeremy L; Albrecht, Randy A; García-Sastre, Adolfo; Katze, Michael G; Waters, Katrina M; Vasconcelos, Daphne; Sabourin, Patrick J; Bresler, Herbert S; Sabourin, Carol L

    2013-06-01

    Infection with pathogenic influenza viruses is associated with intense inflammatory disease. Here, we investigated the innate immune response in mice infected with H5N1 A/Vietnam/1203/04 and with reassortant human H1N1 A/Texas/36/91 viruses containing the virulence genes hemagglutinin (HA), neuraminidase (NA) and NS1 of the 1918 pandemic virus. Inclusion of the 1918 HA and NA glycoproteins rendered a seasonal H1N1 virus capable of inducing an exacerbated host innate immune response similar to that observed for highly pathogenic A/Vietnam/1203/04 virus. Infection with 1918 HA/NA:Tx/91 and A/Vietnam/1203/04 were associated with severe lung pathology, increased cytokine and chemokine production, and significant immune cell changes, including the presence of CD11b(+)Gr-1(+) cells in the blood, lung and bone marrow. Significant differential gene expression in the lung included pathways for cell death, apoptosis, production and response to reactive oxygen radicals, as well as arginine and proline metabolism and chemokines associated with monocyte and neutrophil/granulocyte accumulation and/or activation. Arginase was produced in the lung of animals infected with A/Vietnam/1204. These results demonstrate that the innate immune cell response results in the accumulation of CD11b(+)Gr-1(+) cells and products that have previously been shown to contribute to T cell suppression.

  15. Tissue Distribution and Timing of Appearance of Polytropic Envelope Recombinants during Infection with SL3-3 Murine Leukemia Virus or Its Weakly Pathogenic SL3ΔMyb5 Mutant

    PubMed Central

    Rulli, Karen; Lobelle-Rich, Patricia A.; Trubetskoy, Alla; Lenz, Jack; Levy, Laura S.

    2001-01-01

    A time course analysis was performed to identify the sites of formation and timing of appearance of polytropic recombinant viruses following infection of NIH/Swiss mice with the murine retrovirus SL3-3 murine leukemia virus (SL3) or with a weakly pathogenic mutant termed SL3ΔMyb5. The results indicated that (i) polytropic recombinant viruses occur initially in the thymus of SL3-infected animals, (ii) the timing of appearance of polytropic recombinants in bone marrow is not consistent with their participation in the previously reported formation of transplantable tumor-forming cells at 3 to 4 week postinoculation, and (iii) the efficient generation of recombinant virus is correlated with efficient tumor induction. PMID:11119621

  16. Tissue distribution and timing of appearance of polytropic envelope recombinants during infection with SL3-3 murine leukemia virus or its weakly pathogenic SL3DeltaMyb5 mutant.

    PubMed

    Rulli, K; Lobelle-Rich, P A; Trubetskoy, A; Lenz, J; Levy, L S

    2001-01-01

    A time course analysis was performed to identify the sites of formation and timing of appearance of polytropic recombinant viruses following infection of NIH/Swiss mice with the murine retrovirus SL3-3 murine leukemia virus (SL3) or with a weakly pathogenic mutant termed SL3DeltaMyb5. The results indicated that (i) polytropic recombinant viruses occur initially in the thymus of SL3-infected animals, (ii) the timing of appearance of polytropic recombinants in bone marrow is not consistent with their participation in the previously reported formation of transplantable tumor-forming cells at 3 to 4 week postinoculation, and (iii) the efficient generation of recombinant virus is correlated with efficient tumor induction.

  17. Hepatitis E Virus Infection

    PubMed Central

    Dalton, Harry R.; Abravanel, Florence; Izopet, Jacques

    2014-01-01

    SUMMARY Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. Hepatitis E is an underdiagnosed disease, in part due to the use of serological assays with low sensitivity. However, diagnostic tools, including nucleic acid-based tests, have been improved. The epidemiology and clinical features of hepatitis E differ between developing and developed countries. HEV infection is usually an acute self-limiting disease, but in developed countries it causes chronic infection with rapidly progressive cirrhosis in organ transplant recipients, patients with hematological malignancy requiring chemotherapy, and individuals with HIV. HEV also causes extrahepatic manifestations, including a number of neurological syndromes and renal injury. Acute infection usually requires no treatment, but chronic infection should be treated by reducing immunosuppression in transplant patients and/or the use of antiviral therapy. In this comprehensive review, we summarize the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries. PMID:24396139

  18. Hepatitis E virus infection.

    PubMed

    Kamar, Nassim; Dalton, Harry R; Abravanel, Florence; Izopet, Jacques

    2014-01-01

    Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. Hepatitis E is an underdiagnosed disease, in part due to the use of serological assays with low sensitivity. However, diagnostic tools, including nucleic acid-based tests, have been improved. The epidemiology and clinical features of hepatitis E differ between developing and developed countries. HEV infection is usually an acute self-limiting disease, but in developed countries it causes chronic infection with rapidly progressive cirrhosis in organ transplant recipients, patients with hematological malignancy requiring chemotherapy, and individuals with HIV. HEV also causes extrahepatic manifestations, including a number of neurological syndromes and renal injury. Acute infection usually requires no treatment, but chronic infection should be treated by reducing immunosuppression in transplant patients and/or the use of antiviral therapy. In this comprehensive review, we summarize the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries. PMID:24396139

  19. Virus Infections of Honeybees Apis Mellifera

    PubMed Central

    Tantillo, Giuseppina; Bottaro, Marilisa; Di Pinto, Angela; Martella, Vito; Di Pinto, Pietro

    2015-01-01

    The health and vigour of honeybee colonies are threatened by numerous parasites (such as Varroa destructor and Nosema spp.) and pathogens, including viruses, bacteria, protozoa. Among honeybee pathogens, viruses are one of the major threats to the health and well-being of honeybees and cause serious concern for researchers and beekeepers. To tone down the threats posed by these invasive organisms, a better understanding of bee viral infections will be of crucial importance in developing effective and environmentally benign disease control strategies. Here we summarize recent progress in the understanding of the morphology, genome organization, transmission, epidemiology and pathogenesis of eight honeybee viruses: Deformed wing virus (DWV) and Kakugo virus (KV); Sacbrood virus (SBV); Black Queen cell virus (BQCV); Acute bee paralysis virus (ABPV); Kashmir bee virus (KBV); Israeli Acute Paralysis Virus (IAPV); Chronic bee paralysis virus (CBPV). The review has been designed to provide researchers in the field with updated information about honeybee viruses and to serve as a starting point for future research. PMID:27800411

  20. Differences in pathogenicity, response to vaccination, and innate immune responses in different types of ducks infected with a virulent H5N1 highly pathogenic avian influenza virus from Vietnam

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wild ducks are reservoirs of avian influenza viruses in nature, and usually don’t show signs of disease. However, some Asian lineage H5N1 highly pathogenic avian influenza (HPAI) viruses can cause disease and death in both wild and domestic ducks. The objective of this study was to compare the cli...

  1. [Zika virus infection during pregnancy].

    PubMed

    Picone, O; Vauloup-Fellous, C; D'Ortenzio, E; Huissoud, C; Carles, G; Benachi, A; Faye, A; Luton, D; Paty, M-C; Ayoubi, J-M; Yazdanpanah, Y; Mandelbrot, L; Matheron, S

    2016-05-01

    A Zika virus epidemic is currently ongoing in the Americas. This virus is linked to congenital infections with potential severe neurodevelopmental dysfunction. However, incidence of fetal infection and whether this virus is responsible of other fetal complications are still unknown. National and international public health authorities recommend caution and several prevention measures. Declaration of Zika virus infection is now mandatory in France. Given the available knowledge on Zika virus, we suggest here a review of the current recommendations for management of pregnancy in case of suspicious or infection by Zika virus in a pregnant woman. PMID:27079865

  2. [Zika virus infection during pregnancy].

    PubMed

    Picone, O; Vauloup-Fellous, C; D'Ortenzio, E; Huissoud, C; Carles, G; Benachi, A; Faye, A; Luton, D; Paty, M-C; Ayoubi, J-M; Yazdanpanah, Y; Mandelbrot, L; Matheron, S

    2016-05-01

    A Zika virus epidemic is currently ongoing in the Americas. This virus is linked to congenital infections with potential severe neurodevelopmental dysfunction. However, incidence of fetal infection and whether this virus is responsible of other fetal complications are still unknown. National and international public health authorities recommend caution and several prevention measures. Declaration of Zika virus infection is now mandatory in France. Given the available knowledge on Zika virus, we suggest here a review of the current recommendations for management of pregnancy in case of suspicious or infection by Zika virus in a pregnant woman.

  3. Parainfluenza Virus Infection.

    PubMed

    Branche, Angela R; Falsey, Ann R

    2016-08-01

    Human parainfluenza viruses (HPIVs) are single-stranded, enveloped RNA viruses of the Paramyoviridaie family. There are four serotypes which cause respiratory illnesses in children and adults. HPIVs bind and replicate in the ciliated epithelial cells of the upper and lower respiratory tract and the extent of the infection correlates with the location involved. Seasonal HPIV epidemics result in a significant burden of disease in children and account for 40% of pediatric hospitalizations for lower respiratory tract illnesses (LRTIs) and 75% of croup cases. Parainfluenza viruses are associated with a wide spectrum of illnesses which include otitis media, pharyngitis, conjunctivitis, croup, tracheobronchitis, and pneumonia. Uncommon respiratory manifestations include apnea, bradycardia, parotitis, and respiratory distress syndrome and rarely disseminated infection. Immunity resulting from disease in childhood is incomplete and reinfection with HPIV accounts for 15% of respiratory illnesses in adults. Severe disease and fatal pneumonia may occur in elderly and immunocompromised adults. HPIV pneumonia in recipients of hematopoietic stem cell transplant (HSCT) is associated with 50% acute mortality and 75% mortality at 6 months. Though sensitive molecular diagnostics are available to rapidly diagnose HPIV infection, effective antiviral therapies are not available. Currently, treatment for HPIV infection is supportive with the exception of croup where the use of corticosteroids has been found to be beneficial. Several novel drugs including DAS181 appear promising in efforts to treat severe disease in immunocompromised patients, and vaccines to decrease the burden of disease in young children are in development. PMID:27486735

  4. Molecular Basis of Latency in Pathogenic Human Viruses

    NASA Astrophysics Data System (ADS)

    Garcia-Blanco, Mariano A.; Cullen, Bryan R.

    1991-11-01

    Several human viruses are able to latently infect specific target cell populations in vivo. Analysis of the replication cycles of herpes simplex virus, Epstein-Barr virus, and human immunodeficiency virus suggests that the latent infections established by these human pathogens primarily result from a lack of host factors critical for the expression of viral early gene products. The subsequent activation of specific cellular transcription factors in response to extracellular stimuli can induce the expression of these viral regulatory proteins and lead to a burst of lytic viral replication. Latency in these eukaryotic viruses therefore contrasts with latency in bacteriophage, which is maintained primarily by the expression of virally encoded repressors of lytic replication.

  5. Ebola virus infection modeling and identifiability problems

    PubMed Central

    Nguyen, Van Kinh; Binder, Sebastian C.; Boianelli, Alessandro; Meyer-Hermann, Michael; Hernandez-Vargas, Esteban A.

    2015-01-01

    The recent outbreaks of Ebola virus (EBOV) infections have underlined the impact of the virus as a major threat for human health. Due to the high biosafety classification of EBOV (level 4), basic research is very limited. Therefore, the development of new avenues of thinking to advance quantitative comprehension of the virus and its interaction with the host cells is urgently needed to tackle this lethal disease. Mathematical modeling of the EBOV dynamics can be instrumental to interpret Ebola infection kinetics on quantitative grounds. To the best of our knowledge, a mathematical modeling approach to unravel the interaction between EBOV and the host cells is still missing. In this paper, a mathematical model based on differential equations is used to represent the basic interactions between EBOV and wild-type Vero cells in vitro. Parameter sets that represent infectivity of pathogens are estimated for EBOV infection and compared with influenza virus infection kinetics. The average infecting time of wild-type Vero cells by EBOV is slower than in influenza infection. Simulation results suggest that the slow infecting time of EBOV could be compensated by its efficient replication. This study reveals several identifiability problems and what kind of experiments are necessary to advance the quantification of EBOV infection. A first mathematical approach of EBOV dynamics and the estimation of standard parameters in viral infections kinetics is the key contribution of this work, paving the way for future modeling works on EBOV infection. PMID:25914675

  6. Different routes of inoculation impact infectivity and pathogenesis of H5N1 high pathogenicity avian influenza virus infection in chickens and domestic ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The H5N1 type A influenza viruses classified as Qinghai-like virus (clade 2.2) are a unique lineage of type A influenza viruses with the capacity to produce significant disease and mortality in gallinaceous birds and water fowl including ducks. The objective of this study was to determine the suscep...

  7. A computationally optimized broadly reactive H5 hemagglutinin vaccine provides protection against homologous and heterologous H5N1 highly pathogenic avian influenza virus infection in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since its emergence in 1996 in China, H5N1 highly pathogenic avian influenza (HPAI) virus has continuously evolved into different genetic clades that have created challenges to maintaining antigenically relevant H5N1 vaccine seeds. Therefore, a universal (multi-hemagglutinin [HA] subtype) or more c...

  8. Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

    SciTech Connect

    Perera, Rushika M.; Riley, Catherine; Isaac, Georgis; Hopf- Jannasch, Amber; Moore, Ronald J.; Weitz, Karl K.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.

    2012-03-22

    Dengue virus causes {approx}50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

  9. Detection of Pathogenic Viruses in Sewage Provided Early Warnings of Hepatitis A Virus and Norovirus Outbreaks

    PubMed Central

    Hellmér, Maria; Paxéus, Nicklas; Magnius, Lars; Enache, Lucica; Arnholm, Birgitta; Johansson, Annette; Bergström, Tomas

    2014-01-01

    Most persons infected with enterically transmitted viruses shed large amounts of virus in feces for days or weeks, both before and after onset of symptoms. Therefore, viruses causing gastroenteritis may be detected in wastewater, even if only a few persons are infected. In this study, the presence of eight pathogenic viruses (norovirus, astrovirus, rotavirus, adenovirus, Aichi virus, parechovirus, hepatitis A virus [HAV], and hepatitis E virus) was investigated in sewage to explore whether their identification could be used as an early warning of outbreaks. Samples of the untreated sewage were collected in proportion to flow at Ryaverket, Gothenburg, Sweden. Daily samples collected during every second week between January and May 2013 were pooled and analyzed for detection of viruses by concentration through adsorption to milk proteins and PCR. The largest amount of noroviruses was detected in sewage 2 to 3 weeks before most patients were diagnosed with this infection in Gothenburg. The other viruses were detected at lower levels. HAV was detected between weeks 5 and 13, and partial sequencing of the structural VP1protein identified three different strains. Two strains were involved in an ongoing outbreak in Scandinavia and were also identified in samples from patients with acute hepatitis A in Gothenburg during spring of 2013. The third strain was unique and was not detected in any patient sample. The method used may thus be a tool to detect incipient outbreaks of these viruses and provide early warning before the causative pathogens have been recognized in health care. PMID:25172863

  10. Detection of pathogenic viruses in sewage provided early warnings of hepatitis A virus and norovirus outbreaks.

    PubMed

    Hellmér, Maria; Paxéus, Nicklas; Magnius, Lars; Enache, Lucica; Arnholm, Birgitta; Johansson, Annette; Bergström, Tomas; Norder, Heléne

    2014-11-01

    Most persons infected with enterically transmitted viruses shed large amounts of virus in feces for days or weeks, both before and after onset of symptoms. Therefore, viruses causing gastroenteritis may be detected in wastewater, even if only a few persons are infected. In this study, the presence of eight pathogenic viruses (norovirus, astrovirus, rotavirus, adenovirus, Aichi virus, parechovirus, hepatitis A virus [HAV], and hepatitis E virus) was investigated in sewage to explore whether their identification could be used as an early warning of outbreaks. Samples of the untreated sewage were collected in proportion to flow at Ryaverket, Gothenburg, Sweden. Daily samples collected during every second week between January and May 2013 were pooled and analyzed for detection of viruses by concentration through adsorption to milk proteins and PCR. The largest amount of noroviruses was detected in sewage 2 to 3 weeks before most patients were diagnosed with this infection in Gothenburg. The other viruses were detected at lower levels. HAV was detected between weeks 5 and 13, and partial sequencing of the structural VP1protein identified three different strains. Two strains were involved in an ongoing outbreak in Scandinavia and were also identified in samples from patients with acute hepatitis A in Gothenburg during spring of 2013. The third strain was unique and was not detected in any patient sample. The method used may thus be a tool to detect incipient outbreaks of these viruses and provide early warning before the causative pathogens have been recognized in health care.

  11. Effect of statin treatments on highly pathogenic avian influenza H5N1, seasonal and H1N1pdm09 virus infections in BALB/c mice

    PubMed Central

    Kumaki, Yohichi; Morrey, John D; Barnard, Dale L

    2013-01-01

    Statins are used to control elevated cholesterol or hypercholesterolemia, but have previously been reported to have antiviral properties. Aims To show efficacy of statins in various influenza virus mouse models. Materials & methods BALB/c mice were treated intraperitoneally or orally with several types of statins (simvastatin, lovastatin, mevastatin, pitavastatin, atorvastatin or rosuvastatin) at various concentrations before or after infection with either influenza A/Duck/ MN/1525/81 H5N1 virus, influenza A/Vietnam/1203/2004 H5N1 virus, influenza A/ Victoria/3/75 H3N2 virus, influenza A/NWS/33 H1N1 virus or influenza A/CA/04/09 H1N1pdm09 virus. Results The statins administered intraperitoneally or orally at any dose did not significantly enhance the total survivors relative to untreated controls. In addition, infected mice receiving any concentration of statin were not protected against weight loss due to the infection. None of the statins significantly increased the mean day of death relative to mice in the placebo treatment group. Furthermore, the statins had relatively few ameliorative effects on lung pathology or lung weights at day 3 and 6 after virus exposure, although mice treated with simvastatin did have improved lung function as measured by arterial saturated oxygen levels in one experiment. Conclusion Statins showed relatively little efficacy in any mouse model used by any parameter tested. PMID:23420457

  12. Zika virus infections.

    PubMed

    de Laval, F; Leparc-Goffart, I; Meynard, J-B; Daubigny, H; Simon, F; Briolant, S

    2016-05-01

    Since its discovery in 1947 in Uganda, the Zika virus (ZIKV) remained in the shadows emerging in 2007 in Micronesia, where hundreds of dengue-like syndromes were reported. Then, in 2013-2014, it was rife in French Polynesia, where the first neurological effects were observed. More recently, its arrival in Brazil was accompanied by an unusually high number of children with microcephaly born to mothers infected with ZIKV during the first trimester of pregnancy. In 2016, the World Health Organization declared ZIKV infection to be a public health emergency and now talks about a ZIKV pandemic. This review aims to summarize the current knowledge about ZIKV infection, successively addressing its transmission, epidemiology, clinical aspects, diagnosis, treatment, and prevention before discussing some perspectives. PMID:27412976

  13. Zika virus infections.

    PubMed

    de Laval, F; Leparc-Goffart, I; Meynard, J-B; Daubigny, H; Simon, F; Briolant, S

    2016-05-01

    Since its discovery in 1947 in Uganda, the Zika virus (ZIKV) remained in the shadows emerging in 2007 in Micronesia, where hundreds of dengue-like syndromes were reported. Then, in 2013-2014, it was rife in French Polynesia, where the first neurological effects were observed. More recently, its arrival in Brazil was accompanied by an unusually high number of children with microcephaly born to mothers infected with ZIKV during the first trimester of pregnancy. In 2016, the World Health Organization declared ZIKV infection to be a public health emergency and now talks about a ZIKV pandemic. This review aims to summarize the current knowledge about ZIKV infection, successively addressing its transmission, epidemiology, clinical aspects, diagnosis, treatment, and prevention before discussing some perspectives.

  14. Hazara virus infection is lethal for adult type I interferon receptor-knockout mice and may act as a surrogate for infection with the human-pathogenic Crimean-Congo hemorrhagic fever virus.

    PubMed

    Dowall, Stuart D; Findlay-Wilson, Stephen; Rayner, Emma; Pearson, Geoff; Pickersgill, Janice; Rule, Antony; Merredew, Natasha; Smith, Hazel; Chamberlain, John; Hewson, Roger

    2012-03-01

    Hazara virus (HAZV) is closely related to the Crimean-Congo hemorrhagic fever virus (CCHFV). HAZV has not been reported to cause human disease; work with infectious material can be carried out at containment level (CL)-2. By contrast, CCHFV causes a haemorrhagic fever in humans and requires CL-4 facilities. A disease model of HAZV infection in mice deficient in the type I interferon receptor is reported in this study. Dose-response effects were seen with higher doses, resulting in a shorter time to death and earlier detection of viral loads in organs. The lowest dose of 10 p.f.u. was still lethal in over 50 % of the mice. Histopathological findings were identified in the liver, spleen and lymph nodes, with changes similar to a recent mouse model of CCHFV infection. The findings demonstrate that inoculation of mice with HAZV may act as a useful surrogate model for the testing of antiviral agents against CCHFV.

  15. Giant viruses of amoebae as potential human pathogens.

    PubMed

    Colson, Philippe; La Scola, Bernard; Raoult, Didier

    2013-01-01

    Giant viruses infecting phagocytic protists are composed of mimiviruses, the record holders of particle and genome size amongst viruses, and marseilleviruses. Since the discovery in 2003 at our laboratory of the first of these giant viruses, the Mimivirus, a growing body of data has revealed that they are common inhabitants of our biosphere. Moreover, from the outset, the story of Mimivirus has been linked to that of patients exhibiting pneumonia and it was shown that patients developed antibodies to this amoebal pathogen. Since then, there have been several proven cases of human infection or colonization with giant viruses of amoebae, which are known to host several bacteria that are human pathogens. Mimiviruses and marseilleviruses represent a major challenge in human pathology, as virological procedures implemented to date have not used appropriate media to allow their culture, and molecular techniques have used filtration steps that likely prevented their detection. Nevertheless, there is an increasing body of evidence that mimiviruses might cause pneumonia and that humans carry marseilleviruses, and re-analyses of metagenomic databases have provided evidence that these giant viruses can be common in human samples. The proportion of human infections related to these giant mimiviruses and marseilleviruses and the precise short- and long-term consequences of these infections have been scarcely investigated so far and should be the subject of future works. PMID:24157884

  16. Giant viruses of amoebae as potential human pathogens.

    PubMed

    Colson, Philippe; La Scola, Bernard; Raoult, Didier

    2013-01-01

    Giant viruses infecting phagocytic protists are composed of mimiviruses, the record holders of particle and genome size amongst viruses, and marseilleviruses. Since the discovery in 2003 at our laboratory of the first of these giant viruses, the Mimivirus, a growing body of data has revealed that they are common inhabitants of our biosphere. Moreover, from the outset, the story of Mimivirus has been linked to that of patients exhibiting pneumonia and it was shown that patients developed antibodies to this amoebal pathogen. Since then, there have been several proven cases of human infection or colonization with giant viruses of amoebae, which are known to host several bacteria that are human pathogens. Mimiviruses and marseilleviruses represent a major challenge in human pathology, as virological procedures implemented to date have not used appropriate media to allow their culture, and molecular techniques have used filtration steps that likely prevented their detection. Nevertheless, there is an increasing body of evidence that mimiviruses might cause pneumonia and that humans carry marseilleviruses, and re-analyses of metagenomic databases have provided evidence that these giant viruses can be common in human samples. The proportion of human infections related to these giant mimiviruses and marseilleviruses and the precise short- and long-term consequences of these infections have been scarcely investigated so far and should be the subject of future works.

  17. Bovine respiratory disease model based on dual infections with infection with bovine viral diarrhea virus and bovine corona virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine respiratory disease complex (BRDC) is the leading cause of economic loss in the U.S. cattle industry. BRDC likely results from simultaneous or sequential infections with multiple pathogens including both viruses and bacteria. Bovine viral diarrhea virus (BVDV) and bovine corona virus (BoCV...

  18. Plant virus infections control stomatal development

    PubMed Central

    Murray, Rose R.; Emblow, Mark S. M.; Hetherington, Alistair M.; Foster, Gary D.

    2016-01-01

    Stomata are important regulators of carbon dioxide uptake and transpirational water loss. They also represent points of vulnerability as bacterial and fungal pathogens utilise this natural opening as an entry portal, and thus have an increasingly complex relationship. Unlike the situation with bacterial and fungal pathogens, we know very little about the role of stomata in viral infection. Here we report findings showing that viral infection influences stomatal development in two susceptible host systems (Nicotiana tabacum with TMV (Tobacco mosaic virus), and Arabidopsis thaliana with TVCV (Turnip vein-clearing virus)), but not in resistant host systems (Nicotiana glutinosa and Chenopodium quinoa with TMV). Virus infected plants had significantly lower stomatal indices in systemic leaves of susceptible systems; N. tabacum 9.8% reduction and A. thaliana 12.3% reduction, but not in the resistant hosts. Stomatal density in systemic leaves was also significantly reduced in virus infected A. thaliana by 19.6% but not in N. tabacum or the resistant systems. In addition, transpiration rate was significantly reduced in TMV infected N. tabacum. PMID:27687773

  19. Plant virus infections control stomatal development

    NASA Astrophysics Data System (ADS)

    Murray, Rose R.; Emblow, Mark S. M.; Hetherington, Alistair M.; Foster, Gary D.

    2016-09-01

    Stomata are important regulators of carbon dioxide uptake and transpirational water loss. They also represent points of vulnerability as bacterial and fungal pathogens utilise this natural opening as an entry portal, and thus have an increasingly complex relationship. Unlike the situation with bacterial and fungal pathogens, we know very little about the role of stomata in viral infection. Here we report findings showing that viral infection influences stomatal development in two susceptible host systems (Nicotiana tabacum with TMV (Tobacco mosaic virus), and Arabidopsis thaliana with TVCV (Turnip vein-clearing virus)), but not in resistant host systems (Nicotiana glutinosa and Chenopodium quinoa with TMV). Virus infected plants had significantly lower stomatal indices in systemic leaves of susceptible systems; N. tabacum 9.8% reduction and A. thaliana 12.3% reduction, but not in the resistant hosts. Stomatal density in systemic leaves was also significantly reduced in virus infected A. thaliana by 19.6% but not in N. tabacum or the resistant systems. In addition, transpiration rate was significantly reduced in TMV infected N. tabacum.

  20. Hepatitis B virus infection.

    PubMed

    Chang, Mei-Hwei

    2007-06-01

    Hepatitis B virus (HBV) infection is a worldwide health problem and may cause acute, fulminant, chronic hepatitis, liver cirrhosis, or hepatocelullar carcinoma (HCC). Infection with HBV in infancy or early childhood may lead to a high rate of persistent infection (25-90%), while the rates are lower if infection occurs during adulthood (5-10%). In most endemic areas, infection occurs mainly during early childhood and mother-to-infant transmission accounts for approximately 50% of the chronic infection cases. Hepatitis B during pregnancy does not increase maternal mortality or morbidity or the risk of fetal complications. Approximately 90% of the infants of HBsAg carrier mothers with positive hepatitis B e-antigen (HBeAg) will become carriers if no immunoprophylaxis is given. Transplacental HBeAg may induce a specific non-responsiveness of helper T cells and HBcAg. Spontaneous HBeAg seroconversion to anti-HBe may develop with time but liver damage may occur during the process of the immune clearance of HBV and HBeAg. Mother-to-infant transmission of HBV from HBeAg negative but HBsAg positive mothers is the most important cause of acute or fulminant hepatitis B in infancy. Although antiviral agents are available to treat and avoid the complications of chronic hepatitis B, prevention of HBV infection is the best way for control. Screening for maternal HBsAg with/without HBeAg, followed by three to four doses of HBV vaccine in infancy and hepatitis B immunoglobulin (HBIG) within 24h of birth is the most effective way to prevent HBV infection. In areas with a low prevalence of HBV infection or with limited resources, omitting maternal screening but giving three doses of HBV vaccine universally in infancy can also produce good protective efficacy. The first universal HBV immunisation programme in the world was launched in Taiwan 22 years ago. HBV infection rates, chronicity rates, incidence of HCC and incidence of fulminant hepatitis in children have been effectively

  1. Novel Eurasian highly pathogenic avian influenza A H5 viruses in wild birds, Washington, USA, 2014.

    PubMed

    Ip, Hon S; Torchetti, Mia Kim; Crespo, Rocio; Kohrs, Paul; DeBruyn, Paul; Mansfield, Kristin G; Baszler, Timothy; Badcoe, Lyndon; Bodenstein, Barbara; Shearn-Bochsler, Valerie; Killian, Mary Lea; Pedersen, Janice C; Hines, Nichole; Gidlewski, Thomas; DeLiberto, Thomas; Sleeman, Jonathan M

    2015-05-01

    Novel Eurasian lineage avian influenza A(H5N8) virus has spread rapidly and globally since January 2014. In December 2014, H5N8 and reassortant H5N2 viruses were detected in wild birds in Washington, USA, and subsequently in backyard birds. When they infect commercial poultry, these highly pathogenic viruses pose substantial trade issues.

  2. Novel Eurasian highly pathogenic influenza A H5 viruses in wild birds, Washington, USA

    USGS Publications Warehouse

    Ip, Hon S.; Torchetti, Mia Kim; Crespo, Rocio; Kohrs, Paul; DeBruyn, Paul; Mansfield, Kristin G.; Baszler, Timothy; Badcoe, Lyndon; Bodenstein, Barbara L.; Shearn-Bochsler, Valerie I.; Killian, Mary Lea; Pederson, Janice C.; Hines, Nichole; Gidlewski, Thomas; DeLiberto, Thomas; Sleeman, Jonathan M.

    2015-01-01

    Novel Eurasian lineage avian influenza A(H5N8) virus has spread rapidly and globally since January 2014. In December 2014, H5N8 and reassortant H5N2 viruses were detected in wild birds in Washington, USA, and subsequently in backyard birds. When they infect commercial poultry, these highly pathogenic viruses pose substantial trade issues.

  3. Novel Eurasian Highly Pathogenic Avian Influenza A H5 Viruses in Wild Birds, Washington, USA, 2014

    PubMed Central

    Ip, Hon S.; Crespo, Rocio; Kohrs, Paul; DeBruyn, Paul; Mansfield, Kristin G.; Baszler, Timothy; Badcoe, Lyndon; Bodenstein, Barbara; Shearn-Bochsler, Valerie; Killian, Mary Lea; Pedersen, Janice C.; Hines, Nichole; Gidlewski, Thomas; DeLiberto, Thomas; Sleeman, Jonathan M.

    2015-01-01

    Novel Eurasian lineage avian influenza A(H5N8) virus has spread rapidly and globally since January 2014. In December 2014, H5N8 and reassortant H5N2 viruses were detected in wild birds in Washington, USA, and subsequently in backyard birds. When they infect commercial poultry, these highly pathogenic viruses pose substantial trade issues. PMID:25898265

  4. Hepatitis E virus as an emerging zoonotic pathogen

    PubMed Central

    Park, Woo-Jung; Park, Byung-Joo; Ahn, Hee-Seop; Lee, Joong-Bok; Park, Seung-Yong; Song, Chang-Seon; Lee, Sang-Won; Yoo, Han-Sang

    2016-01-01

    Hepatitis E outbreaks are a serious public health concern in developing countries. The disease causes acute infections, primarily in young adults. The mortality rate is approximately 2%; however, it can exceed 20% in pregnant women in some regions in India. The causative agent, hepatitis E virus (HEV), has been isolated from several animal species, including pigs. HEV genotypes 3 and 4 have been isolated from both humans and animals, and are recognized as zoonotic pathogens. Seroprevalence studies in animals and humans indirectly suggest that HEV infections occur worldwide. The virus is primarily transmitted to humans via undercooked animal meats in developed countries. Moreover, transfusion- and transplantation-mediated HEV infections have recently been reported. This review summarizes the general characteristics of hepatitis E, HEV infection status in animals and humans, the zoonotic transmission modes of HEV, and HEV vaccine development status. PMID:27051334

  5. The role of respiratory syncytial virus and other viral pathogens in acute otitis media.

    PubMed

    Klein, B S; Dollete, F R; Yolken, R H

    1982-07-01

    We utilized recently developed enzyme immunoassay techniques to examine the role of selected viruses in the etiology of acute otitis media. Viral pathogens were found in middle ear fluids obtained from 13 (24%) of 53 children with acute otitis media; respiratory syncytial virus accounted for ten of the 13 viral agents identified. In addition, respiratory syncytial viral antigen was found in nasopharyngeal washings obtained from 15 of the 53 children. Seven of these children had RSV identified as the sole middle ear pathogen, whereas six children had otitis caused by Streptococcus pneumoniae as either the sole middle ear pathogen or in combination with RSV. Similarly, all three children with respiratory infections caused by influenza virus had ear infections caused by bacterial pathogens, either alone or in combination with influenza virus. These findings suggest that, in patients with viral respiratory infection, coexisting acute otitis media may be associated with the recovery of either viruses or bacteria from the middle ear exudates.

  6. Autoimmune pathogenesis in dengue virus infection.

    PubMed

    Lin, Chiou-Feng; Wan, Shu-Wen; Cheng, Hsien-Jen; Lei, Huan-Yao; Lin, Yee-Shin

    2006-01-01

    The pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) caused by dengue virus (DV) infection remain unresolved. Patients with DHF/DSS are characterized by several manifestations, including severe thrombocytopenia, vascular leakage, and hepatomegaly. In addition to the effect of virus load and virus variation, abnormal immune responses of the host after DV infection may also account for the progression of DHF/DSS. Actually, viral autoimmunity is involved in the pathogenesis of numerous viral infections, such as human immunodeficiency virus, human hepatitis C virus, human cytomegalovirus, herpes simplex virus, Epstein- Barr virus, and DV. In this review, we discuss the implications of autoimmunity in dengue pathogenesis. Antibodies directed against DV nonstructural protein 1 (NS1) showed cross-reactivity with human platelets and endothelial cells, which lead to platelet and endothelial cell damage and inflammatory activation. Based on these findings, we hypothesize that anti-DV NS1 is involved in the pathogenesis of DF and DHF/DSS, and this may provide important information in dengue vaccine development.

  7. Virus infection and knee injury.

    PubMed Central

    Driscoll, P; Venner, R; Clements, G B

    1987-01-01

    Serological evidence of virus infection was sought in 31 consecutive patients presenting with knee swelling and compared with age/sex-matched controls. In a normal age/sex-matched control group, 42% of patients had evidence of recent or past infection with Coxsackie B virus, emphasising the care required in the evaluation of the significance of Coxsackie B neutralization titres in individual patients. Of 12 patients presenting with knee swelling and a history of a twisting injury, eight had serological evidence of recent or past infection with Coxsackie B virus, and one had evidence of a current adenovirus infection. PMID:2825728

  8. The role of carbohydrates in infection strategies of enteric pathogens.

    PubMed

    Kato, Kentaro; Ishiwa, Akiko

    2015-03-01

    Enteric pathogens cause considerable public health concerns worldwide including tropical regions. Here, we review the roles of carbohydrates in the infection strategies of various enteric pathogens including viruses, bacteria and protozoa, which infect the epithelial lining of the human and animal intestine. At host cell entry, enteric viruses, including norovirus, recognize mainly histo-blood group antigens. At the initial step of bacterial infections, carbohydrates also function as receptors for attachment. Here, we describe the function of carbohydrates in infection by Salmonella enterica and several bacterial species that produce a variety of fimbrial adhesions. During invasion by enteropathogenic protozoa, apicomplexan parasites utilize sialic acids or sulfated glycans. Carbohydrates serve as receptors for infection by these microbes; however, their usage of carbohydrates varies depending on the microbe. On the surface of the mucosal tissues of the gastrointestinal tract, various carbohydrate moieties are present and play a crucial role in infection, representing the site of infection or route of access for most microbes. During the infection and/or invasion process of the microbes, carbohydrates function as receptors for various microbes, but they can also function as a barrier to infection. One approach to develop effective prophylactic and therapeutic antimicrobial agents is to modify the drug structure. Another approach is to modify the mode of inhibition of infection depending on the individual pathogen by using and mimicking the interactions with carbohydrates. In addition, similarities in mode of infection may also be utilized. Our findings will be useful in the development of new drugs for the treatment of enteric pathogens. PMID:25859152

  9. Laser inactivation of pathogenic viruses in water

    NASA Astrophysics Data System (ADS)

    Grishkanich, Alexander; Zhevlakov, Alexander; Kascheev, Sergey; Sidorov, Igor; Ruzankina, Julia; Yakovlev, Alexey; Mak, Andrey

    2016-03-01

    Currently there is a situation that makes it difficult to provide the population with quality drinking water for the sanitary-hygienic requirements. One of the urgent problems is the need for water disinfection. Since the emergence of microorganisms that are pathogens transmitted through water such as typhoid, cholera, etc. requires constant cleansing of waters against pathogenic bacteria. In the water treatment process is destroyed up to 98% of germs, but among the remaining can be pathogenic viruses, the destruction of which requires special handling. As a result, the conducted research the following methods have been proposed for combating harmful microorganisms: sterilization of water by laser radiation and using a UV lamp.

  10. Multiple infections of rodents with zoonotic pathogens in Austria.

    PubMed

    Schmidt, Sabrina; Essbauer, Sandra S; Mayer-Scholl, Anne; Poppert, Sven; Schmidt-Chanasit, Jonas; Klempa, Boris; Henning, Klaus; Schares, Gereon; Groschup, Martin H; Spitzenberger, Friederike; Richter, Dania; Heckel, Gerald; Ulrich, Rainer G

    2014-07-01

    Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host-pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans.

  11. Multiple Infections of Rodents with Zoonotic Pathogens in Austria

    PubMed Central

    Schmidt, Sabrina; Essbauer, Sandra S.; Mayer-Scholl, Anne; Poppert, Sven; Schmidt-Chanasit, Jonas; Klempa, Boris; Henning, Klaus; Schares, Gereon; Groschup, Martin H.; Spitzenberger, Friederike; Richter, Dania; Heckel, Gerald

    2014-01-01

    Abstract Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host–pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans. PMID

  12. Multiple infections of rodents with zoonotic pathogens in Austria.

    PubMed

    Schmidt, Sabrina; Essbauer, Sandra S; Mayer-Scholl, Anne; Poppert, Sven; Schmidt-Chanasit, Jonas; Klempa, Boris; Henning, Klaus; Schares, Gereon; Groschup, Martin H; Spitzenberger, Friederike; Richter, Dania; Heckel, Gerald; Ulrich, Rainer G

    2014-07-01

    Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host-pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans. PMID:24915446

  13. Aedes Mosquito Saliva Modulates Rift Valley Fever Virus Pathogenicity

    PubMed Central

    Le Coupanec, Alain; Babin, Divya; Fiette, Laurence; Jouvion, Grégory; Ave, Patrick; Misse, Dorothee; Bouloy, Michèle; Choumet, Valerie

    2013-01-01

    Background Rift Valley fever (RVF) is a severe mosquito-borne disease affecting humans and domestic ruminants. Mosquito saliva contains compounds that counteract the hemostatic, inflammatory, and immune responses of the host. Modulation of these defensive responses may facilitate virus infection. Indeed, Aedes mosquito saliva played a crucial role in the vector's capacity to effectively transfer arboviruses such as the Cache Valley and West Nile viruses. The role of mosquito saliva in the transmission of Rift Valley fever virus (RVFV) has not been investigated. Objective Using a murine model, we explored the potential for mosquitoes to impact the course of RVF disease by determining whether differences in pathogenesis occurred in the presence or absence of mosquito saliva and salivary gland extract. Methods C57BL/6NRJ male mice were infected with the ZH548 strain of RVFV via intraperitoneal or intradermal route, or via bites from RVFV-exposed mosquitoes. The virus titers in mosquitoes and mouse organs were determined by plaque assays. Findings After intraperitoneal injection, RVFV infection primarily resulted in liver damage. In contrast, RVFV infection via intradermal injection caused both liver and neurological symptoms and this route best mimicked the natural infection by mosquitoes. Co-injections of RVFV with salivary gland extract or saliva via intradermal route increased the mortality rates of mice, as well as the virus titers measured in several organs and in the blood. Furthermore, the blood cell counts of infected mice were altered compared to those of uninfected mice. Interpretation Different routes of infection determine the pattern in which the virus spreads and the organs it targets. Aedes saliva significantly increases the pathogenicity of RVFV. PMID:23785528

  14. [BK virus infections in kidney transplantation].

    PubMed

    Lanot, Antoine; Bouvier, Nicolas; Chatelet, Valérie; Dina, Julia; Béchade, Clémence; Ficheux, Maxence; Henri, Patrick; Lobbedez, Thierry; Hurault de Ligny, Bruno

    2016-04-01

    BK virus is near ubiquitous, with a seroprevalence of around 80% in the general population. Subsequent to an asymptomatic primary infection, BK virus then remains dormant in healthy subjects. Reactivation occurs in immunocompromised people. BKv is pathogenic mainly among patients who have received a kidney transplant, in whom the virus can cause specific tubulo-interstitial nephritis and even result in graft failure among approximately 20 to 30% of nephritic cases. Since the mid 90 s, incidence has increased with the use of new powerful immunosuppressor treatments. The cornerstone of BK virus infection or BK virus-associated nephropathy treatment is a decrease of the immunosuppressive regimen, which must then be offset with the risk of rejection. The use of several adjuvant therapies has been submitted (fluoroquinolones, leflunomide, intravenous immunoglobulins, cidofovir), with no sufficient proof enabling the recommendation of first-line prescription. The high frequency of this infection and its potential harmfulness argue for the use of prevention strategies, at least among patients presenting risk factors. Retransplantation is safe after a first kidney allograft loss caused by BK-virus nephropathy, on condition that a screening for viremia is frequently conducted.

  15. [BK virus infections in kidney transplantation].

    PubMed

    Lanot, Antoine; Bouvier, Nicolas; Chatelet, Valérie; Dina, Julia; Béchade, Clémence; Ficheux, Maxence; Henri, Patrick; Lobbedez, Thierry; Hurault de Ligny, Bruno

    2016-04-01

    BK virus is near ubiquitous, with a seroprevalence of around 80% in the general population. Subsequent to an asymptomatic primary infection, BK virus then remains dormant in healthy subjects. Reactivation occurs in immunocompromised people. BKv is pathogenic mainly among patients who have received a kidney transplant, in whom the virus can cause specific tubulo-interstitial nephritis and even result in graft failure among approximately 20 to 30% of nephritic cases. Since the mid 90 s, incidence has increased with the use of new powerful immunosuppressor treatments. The cornerstone of BK virus infection or BK virus-associated nephropathy treatment is a decrease of the immunosuppressive regimen, which must then be offset with the risk of rejection. The use of several adjuvant therapies has been submitted (fluoroquinolones, leflunomide, intravenous immunoglobulins, cidofovir), with no sufficient proof enabling the recommendation of first-line prescription. The high frequency of this infection and its potential harmfulness argue for the use of prevention strategies, at least among patients presenting risk factors. Retransplantation is safe after a first kidney allograft loss caused by BK-virus nephropathy, on condition that a screening for viremia is frequently conducted. PMID:26827190

  16. Modeling Dental Health Care Workers' Risk of Occupational Infection from Bloodborne Pathogens.

    ERIC Educational Resources Information Center

    Capilouto, Eli; And Others

    1990-01-01

    The brief paper offers a model which permits quantification of the dental health care workers' risk of occupationally acquiring infection from bloodborne pathogens such as human immunodeficiency virus and hepatitis B virus. The model incorporates five parameters such as the probability that any individual patient is infected and number of patients…

  17. Human Immunodeficiency Virus (HIV) Primary Infection

    MedlinePlus

    ... rashes clinical tools newsletter | contact Share | Human Immunodeficiency Virus (HIV) Primary Infection Information for adults A A ... weeks following exposure to HIV (the human immunodeficiency virus). Chronic infection with this virus can cause AIDS ( ...

  18. Determinants of pathogenicity of H5N1 highly pathogenic avian influenza viruses in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks have been implicated in the dissemination and evolution of the H5N1 highly pathogenic avian influenza (HPAI) viruses. The pathogenicity of H5N1 HPAI viruses in domestic ducks has increased over time with some viruses producing 100% mortality in very short time. The determinants of pathogenic...

  19. Differential transcription of fathead minnow immune-related genes following infection with frog virus 3, an emerging pathogen of ectothermic vertebrates.

    PubMed

    Cheng, Kwang; Escalon, B Lynn; Robert, Jacques; Chinchar, V Gregory; Garcia-Reyero, Natàlia

    2014-05-01

    Frog virus 3 (FV3) and other ranaviruses are responsible for die-offs involving wild, farmed, and captive amphibians, fish, and reptiles. To ascertain which elements of the immune system respond to infection, we explored transcriptional responses following infection of fathead minnow cells with either wild type (wt) FV3 or a knock out (KO) mutant targeting the 18 kDa immediate early gene (18K). At 8h post infection we observed marked upregulation of multiple transcripts encoding proteins affecting innate and acquired immunity. Sequences expressed 4-fold or higher in wt-infected cells included transcripts encoding interferon (IFN), IFN regulatory factors (IRFs), IFN stimulated genes (ISGs) such as Mx and MHC class I, and interleukins IL-1β, IL-8, IL-17C and IL-12. Cells infected with the 18K KO mutant (∆18K) showed qualitative differences and lower levels of induction. Collectively, these results indicate that ranavirus infection induced expression of multiple cellular genes affecting both innate and acquired immunity.

  20. Respiratory Syncytial Virus Infections

    MedlinePlus

    Respiratory syncytial virus (RSV) causes mild, cold-like symptoms in adults and older healthy children. It can cause serious problems in ... tests can tell if your child has the virus. There is no specific treatment. You should give ...

  1. Pathogenesis of human immunodeficiency virus infection.

    PubMed Central

    Levy, J A

    1993-01-01

    The lentivirus human immunodeficiency virus (HIV) causes AIDS by interacting with a large number of different cells in the body and escaping the host immune response against it. HIV is transmitted primarily through blood and genital fluids and to newborn infants from infected mothers. The steps occurring in infection involve an interaction of HIV not only with the CD4 molecule on cells but also with other cellular receptors recently identified. Virus-cell fusion and HIV entry subsequently take place. Following virus infection, a variety of intracellular mechanisms determine the relative expression of viral regulatory and accessory genes leading to productive or latent infection. With CD4+ lymphocytes, HIV replication can cause syncytium formation and cell death; with other cells, such as macrophages, persistent infection can occur, creating reservoirs for the virus in many cells and tissues. HIV strains are highly heterogeneous, and certain biologic and serologic properties determined by specific genetic sequences can be linked to pathogenic pathways and resistance to the immune response. The host reaction against HIV, through neutralizing antibodies and particularly through strong cellular immune responses, can keep the virus suppressed for many years. Long-term survival appears to involve infection with a relatively low-virulence strain that remains sensitive to the immune response, particularly to control by CD8+ cell antiviral activity. Several therapeutic approaches have been attempted, and others are under investigation. Vaccine development has provided some encouraging results, but the observations indicate the major challenge of preventing infection by HIV. Ongoing research is necessary to find a solution to this devastating worldwide epidemic. Images PMID:8464405

  2. Lack of Interleukin-10-Mediated Anti-Inflammatory Signals and Upregulated Interferon Gamma Production Are Linked to Increased Intestinal Epithelial Cell Apoptosis in Pathogenic Simian Immunodeficiency Virus Infection

    PubMed Central

    Pan, Diganta; Kenway-Lynch, Carys S.; Lala, Wendy; Veazey, Ronald S.; Lackner, Andrew A.; Das, Arpita

    2014-01-01

    ABSTRACT Interleukin-10 (IL-10) is an immunomodulatory cytokine that is important for maintenance of epithelial cell (EC) survival and anti-inflammatory responses (AIR). The majority of HIV infections occur through the mucosal route despite mucosal epithelium acting as a barrier to human immunodeficiency virus (HIV). Therefore, understanding the role of IL-10 in maintenance of intestinal homeostasis during HIV infection is of interest for better characterization of the pathogenesis of HIV-mediated enteropathy. We demonstrated here changes in mucosal IL-10 signaling during simian immunodeficiency virus (SIV) infection in rhesus macaques. Disruption of the epithelial barrier was manifested by EC apoptosis and loss of the tight-junction protein ZO-1. Multiple cell types, including a limited number of ECs, produced IL-10. SIV infection resulted in increased levels of IL-10; however, this was associated with increased production of mucosal gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), suggesting that IL-10 was not able to regulate AIR. This observation was supported by the downregulation of STAT3, which is necessary to inhibit production of IFN-γ and TNF-α, and the upregulation of SOCS1 and SOCS3, which are important regulatory molecules in the IL-10-mediated AIR. We also observed internalization of the IL-10 receptor (IL-10R) in mucosal lymphocytes, which could limit cellular availability of IL-10 for signaling and contribute to the loss of a functional AIR. Collectively, these findings demonstrate that internalization of IL-10R with the resultant impact on IL-10 signaling and dysregulation of the IL-10-mediated AIR might play a crucial role in EC damage and subsequent SIV/HIV pathogenesis. IMPORTANCE Interleukin-10 (IL-10), an important immunomodulatory cytokine plays a key role to control inflammatory function and homeostasis of the gastrointestinal mucosal immune system. Despite recent advancements in the study of IL-10 and its role in HIV

  3. IFITMs restrict the replication of multiple pathogenic viruses

    PubMed Central

    Perreira, Jill M.; Chin, Christopher R.; Feeley, Eric M.; Brass, Abraham L.

    2014-01-01

    The IFITM family of proteins inhibit a growing number of pathogenic viruses, among them influenza A virus, dengue virus, hepatitis C virus, and Ebola virus. This review covers recent developments in our understanding of the IFITM’s molecular determinants, potential mechanisms of action, and impact on pathogenesis. PMID:24076421

  4. Leading edge analysis of transcriptomic changes during pseudorabies virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eight RNA samples taken from the tracheobronchial lymph nodes (TBLN) of pigs that were either infected or non-infected with a feral isolate of porcine pseudorabies virus (PRV) were used to investigate changes in gene expression related to the pathogen. The RNA was processed into fastq files for each...

  5. Control of pathogenic effector T-cell activities in situ by PD-L1 expression on respiratory inflammatory dendritic cells during respiratory syncytial virus infection

    PubMed Central

    Yao, S; Jiang, L; Moser, EK; Jewett, LB; Wright, J; Du, J; Zhou, B; Davis, SD; Krupp, NL; Braciale, TJ; Sun, J

    2015-01-01

    Respiratory syncytial virus (RSV) infection is a leading cause of severe lower respiratory tract illness in young infants, the elderly and immunocompromised individuals. We demonstrate here that the co-inhibitory molecule programmed cell death 1 (PD-1) is selectively upregulated on T cells within the respiratory tract during both murine and human RSV infection. Importantly, the interaction of PD-1 with its ligand PD-L1 is vital to restrict the pro-inflammatory activities of lung effector T cells in situ, thereby inhibiting the development of excessive pulmonary inflammation and injury during RSV infection. We further identify that PD-L1 expression on lung inflammatory dendritic cells is critical to suppress inflammatory T-cell activities, and an interferon–STAT1–IRF1 axis is responsible for increased PD-L1 expression on lung inflammatory dendritic cells. Our findings suggest a potentially critical role of PD-L1 and PD-1 interactions in the lung for controlling host inflammatory responses and disease progression in clinical RSV infection. PMID:25465101

  6. Poultry vaccination directed evolution of H9N2 low pathogenicity avian influenza viruses in Korea

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Significant economic losses in the poultry industries have resulted from H9N2 low pathogenic avian influenza virus infections across North Africa, the Middle East and Asia. The present study investigated the evolutionary dynamics of H9N2 viruses circulating in Korea from 1996 to 2012. Our analysis o...

  7. Rapidly Expanding Range of Highly Pathogenic Avian Influenza Viruses.

    PubMed

    Hall, Jeffrey S; Dusek, Robert J; Spackman, Erica

    2015-07-01

    The movement of highly pathogenic avian influenza (H5N8) virus across Eurasia and into North America and the virus' propensity to reassort with co-circulating low pathogenicity viruses raise concerns among poultry producers, wildlife biologists, aviculturists, and public health personnel worldwide. Surveillance, modeling, and experimental research will provide the knowledge required for intelligent policy and management decisions.

  8. Infections Associated with Health-care Personnel: Vaccine-preventable Diseases and Bloodborne Pathogens.

    PubMed

    Kuehnert; Cardo

    2000-12-01

    Health-care personnel (HCP) are at risk for infection from occupational exposure, and can transmit infectious pathogens to patients and other personnel. The risk of disease acquisition depends on factors including the virulence of the causative organism, the mode of pathogen transmission, and the immune competency of the exposed individual. This article reviews the management of occupational exposure, infection, and strategies for the prevention of transmission of selected vaccine-prevent- able diseases (varicella zoster virus, influenza, pertussis) and bloodborne pathogens (hepatitis B virus, hepatitis C virus, human immunodeficiency virus). Recommended strategies include surveillance, vaccination, infection control measures, and postexposure prophylaxis. Improved detection, management, and prevention strategies are needed to reduce the risk of trans- mission of infection to HCP.

  9. Development of a consensus microarray method for identification of some highly pathogenic viruses.

    PubMed

    Xiao-Ping, Kang; Yong-Qiang, Li; Qing-Ge, Sun; Hong, Liu; Qing-Yu, Zhu; Yin-Hui, Yang

    2009-11-01

    Some highly pathogenic viruses, such as Chikungunya virus, Japanese encephalitis virus, Yellow fever virus, Dengue virus, Hanta virus, SARS-CoV, and H5N1 avian influenza virus can cause severe infectious diseases. However, the consensus method for detecting these viruses has not been well established. A rapid and sensitive microarray approach for detection of these viruses and a panel of specific probes covering nine genera and 16 virus species were designed. 70-mer oligonucleotides were used at the genus level and 50-mer oligonucleotides were at the species level, respectively. To decrease the interference of the host genome in hybridization, the consensus genus primers were designed and used to reverse transcribe only virus genome. The synthesis of the second strand was carried out with a random primer sequence (5'-GTTTCCCAGTAGGTCTCNNNNNNNN-3'). The amplified products were labeled and processed for microarray analyses. This microarray-based method used the highly conserved consensus primers to synthesize specifically the virus cDNA and could identify effectively Chikungunya virus, Japanese encephalitis virus, Yellow fever virus, Dengue virus, Tick borne encephalitis virus, and H5N1 avian influenza virus. Using this method, one unknown virus isolated from pig brain in Shanxi Province, China was identified. This method may have an important potential application for the diagnosis of virus infection.

  10. Microgravity Analogues of Herpes Virus Pathogenicity: Human Cytomegalovirus (hCMV) and Varicella Zoster (VZV) Infectivity in Human Tissue Like Assemblies (TLAs)

    NASA Technical Reports Server (NTRS)

    Goodwin, T. J.; McCarthy, M.; Albrecht, T.; Cohrs, R.

    2009-01-01

    The old adage we are our own worst enemies may perhaps be the most profound statement ever made when applied to man s desire for extraterrestrial exploration and habitation of Space. Consider the immune system protects the integrity of the entire human physiology and is comprised of two basic elements the adaptive or circulating and the innate immune system. Failure of the components of the adaptive system leads to venerability of the innate system from opportunistic microbes; viral, bacteria, and fungal, which surround us, are transported on our skin, and commonly inhabit the human physiology as normal and imunosuppressed parasites. The fine balance which is maintained for the preponderance of our normal lives, save immune disorders and disease, is deregulated in microgravity. Thus analogue systems to study these potential Risks are essential for our progress in conquering Space exploration and habitation. In this study we employed two known physiological target tissues in which the reactivation of hCMV and VZV occurs, human neural and lung systems created for the study and interaction of these herpes viruses independently and simultaneously on the innate immune system. Normal human neural and lung tissue analogues called tissue like assemblies (TLAs) were infected with low MOIs of approximately 2 x 10(exp -5) pfu hCMV or VZV and established active but prolonged low grade infections which spanned .7-1.5 months in length. These infections were characterized by the ability to continuously produce each of the viruses without expiration of the host cultures. Verification and quantification of viral replication was confirmed via RT_PCR, IHC, and confocal spectral analyses of the respective essential viral genomes. All host TLAs maintained the ability to actively proliferate throughout the entire duration of the experiments as is analogous to normal in vivo physiological conditions. These data represent a significant advance in the ability to study the triggering

  11. Pathogenicity of a currently circulating Chinese variant pseudorabies virus in pigs

    PubMed Central

    Yang, Qing-Yuan; Sun, Zhe; Tan, Fei-Fei; Guo, Ling-Hua; Wang, Yu-Zhou; Wang, Juan; Wang, Zhi-Yan; Wang, Li-Lin; Li, Xiang-Dong; Xiao, Yan; Tian, Ke-Gong

    2016-01-01

    AIM: To test the pathogenicity of pseudorabies virus (PRV) variant HN1201 and compare its pathogenicity with a classical PRV Fa strain. METHODS: The pathogenicity of the newly-emerging PRV variant HN1201 was evaluated by different inoculating routes, virus loads, and ages of pigs. The classical PRV Fa strain was then used to compare with HN1201 to determine pathogenicity. Clinical symptoms after virus infection were recorded daily and average daily body weight was used to measure the growth performance of pigs. At necropsy, gross pathology and histopathology were used to evaluate the severity of tissue damage caused by virus infection. RESULTS: The results showed that the efficient infection method of RPV HN1201 was via intranasal inoculation at 107 TCID50, and that the virus has high pathogenicity to 35- to 127-d old pigs. Compared with Fa strain, pigs infected with HN1201 showed more severe clinical symptoms and pathological lesions. Immunochemistry results revealed HN1201 had more abundant antigen distribution in extensive organs. CONCLUSION: All of the above results suggest that PRV variant HN1201 was more pathogenic to pigs than the classical Fa strain. PMID:26870671

  12. Unfolded protein response in hepatitis C virus infection

    PubMed Central

    Chan, Shiu-Wan

    2014-01-01

    Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus of clinical importance. The virus establishes a chronic infection and can progress from chronic hepatitis, steatosis to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The mechanisms of viral persistence and pathogenesis are poorly understood. Recently the unfolded protein response (UPR), a cellular homeostatic response to endoplasmic reticulum (ER) stress, has emerged to be a major contributing factor in many human diseases. It is also evident that viruses interact with the host UPR in many different ways and the outcome could be pro-viral, anti-viral or pathogenic, depending on the particular type of infection. Here we present evidence for the elicitation of chronic ER stress in HCV infection. We analyze the UPR signaling pathways involved in HCV infection, the various levels of UPR regulation by different viral proteins and finally, we propose several mechanisms by which the virus provokes the UPR. PMID:24904547

  13. Pathogenicity of two Egyptian H5N1 highly pathogenic avian influenza viruses in domestic ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Domestic ducks have been implicated in the dissemination and evolution of H5N1 highly pathogenic avian influenza (HPAI) viruses. Interestingly, the pathogenicity of H5N1 HPAI viruses in domestic ducks has increased over time with some viruses producing 100% mortality in ducks. These changes in vir...

  14. Equine infectious anemia in mules: virus isolation and pathogenicity studies.

    PubMed

    Spyrou, V; Papanastassopoulou, M; Psychas, V; Billinis, Ch; Koumbati, M; Vlemmas, J; Koptopoulos, G

    2003-08-29

    There appears to be a lack of information concerning responses of mules to natural infection or experimental inoculation with equine infectious anemia virus (EIAV). In the present study EIAV was isolated from mules, for the first time, and its pathogenicity in naturally infected and experimentally inoculated animals was investigated. Two naturally infected (A and B) and three EIAV free mules (C, D and E) were used for this purpose. Mule A developed clinical signs, whereas mule B remained asymptomatic until the end of the study. Mules C and D were each inoculated with 10ml of blood from mule A and developed signs of the disease; they were euthanatized or died at day 22 and 25 post-inoculation, respectively. Mule E served as a negative control. The virus was isolated from the plasma samples of mules with clinical signs of the disease (A, C and D), but not from the asymptomatic mule B. Both proviral DNA and viral RNA were amplified from blood and tissues of the infected animals by nested polymerase chain reaction (nPCR). Antibodies were not detected in the two experimentally infected mules until their natural death or euthanasia. Clinicopathological and laboratory findings showed that, in mules, EIAV produced clinical signs similar to those observed in horses and ponies. Nested PCR proved to be a rapid, sensitive and specific diagnostic method for the detection of EIAV, regardless of the disease stage.

  15. Plasmopara halstedii virus causes hypovirulence in Plasmopara halstedii, the downy mildew pathogen of the sunflower.

    PubMed

    Grasse, Wolfgang; Zipper, Reinhard; Totska, Maria; Spring, Otmar

    2013-08-01

    Plasmopara halstedii virus (PhV) is an isometric virus recently found in the oomycete Plasmopara halstedii. The fully sequenced virus genome consists of two ss(+)RNA strands encoding for the virus polymerase and the coat protein, respectively. Most of previously screened field isolates of P. halstedii were found to harbor PhV, but effects of PhV on the pathogenicity and aggressiveness of the oomycete have not been investigated yet. To assess the influence of PhV on the infectivity of P. halstedii, virus-free isolates of the oomycete were searched for, cultivated on sunflower and used for single zoospore infection. Four genetically homogenous strains belonging to three different pathotypes (710, 730, 750) were established. Subcultures of each strain were successfully infected with PhV. This afforded pairs of isogenic strains with and without virus and allowed assessment of the pathogenicity (susceptibility to specific sunflower genotypes) and aggressiveness (intensity of infection, time scale and density of sporulation) in cultivation of sunflower. While no significant difference was found in the pathogenicity of P. halstedii strains with and without virus towards sunflower seedlings of different resistance (pathotype differentials), the aggressiveness of the oomycete was diminished by PhV. Compared to the virus-free strains, the time required for the first sporulation (latent period) increased by about 1 day post inoculation. Progression of the pathogen from the hypocotyl into the epicotyl of sunflower (systemic infection) was reduced by about one third in the presence of virus. In the virus containing strains, the average density of sporangia produced per cm² cotyledon reached only 75% of the virus-free controls. In summary, the presence of PhV leads to hypovirulence effects by weakening the aggressiveness of P. halstedii. PMID:23747662

  16. Nonpathogenic Simian Immunodeficiency Virus Infections

    PubMed Central

    Klatt, Nichole R.; Silvestri, Guido; Hirsch, Vanessa

    2012-01-01

    The simian immunodeficiency viruses (SIVs) are a diverse group of viruses that naturally infect a wide range of African primates, including African green monkeys (AGMs) and sooty mangabey monkeys (SMs). Although natural infection is widespread in feral populations of AGMs and SMs, this infection generally does not result in immunodeficiency. However, experimental inoculation of Asian macaques results in an immunodeficiency syndrome remarkably similar to human AIDS. Thus, natural nonprogressive SIV infections appear to represent an evolutionary adaptation between these animals and their primate lentiviruses. Curiously, these animals maintain robust virus replication but have evolved strategies to avoid disease progression. Adaptations observed in these primates include phenotypic changes to CD4+ T cells, limited chronic immune activation, and altered mucosal immunity. It is probable that these animals have achieved a unique balance between T-cell renewal and proliferation and loss through activation-induced apoptosis, and virus-induced cell death. A clearer understanding of the mechanisms underlying the lack of disease progression in natural hosts for SIV infection should therefore yield insights into the pathogenesis of AIDS and may inform vaccine design. PMID:22315718

  17. Airborne transmission of H5N1 high pathogenicity avian influenza viruses during simulated home slaughter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most H5N1 human infections have occurred following exposure to H5N1 high pathogenicity avian influenza (HPAI) virus-infected poultry, especially when poultry are home slaughtered or slaughtered in live poultry markets. Previous studies have demonstrated that slaughter of clade 1 isolate A/Vietnam/1...

  18. Characterization of low-pathogenicity H5N1 avian influenza viruses from North America

    USGS Publications Warehouse

    Spackman, Erica; Swayne, D.E.; Suarez, D.L.; Senne, D.A.; Pedersen, J.C.; Killian, M.L.; Pasick, J.; Handel, K.; Pillai, S.P.S.; Lee, C.-W.; Stallknecht, D.; Slemons, R.; Ip, H.S.; Deliberto, T.

    2007-01-01

    Wild-bird surveillance in North America for avian influenza (AI) viruses with a goal of early identification of the Asian H5N1 highly pathogenic AI virus has identified at least six low-pathogenicity H5N1 AI viruses between 2004 and 2006. The hemagglutinin (HA) and neuraminidase (NA) genes from all 6 H5N1 viruses and an additional 38 North American wild-bird-origin H5 subtype and 28 N1 subtype viruses were sequenced and compared with sequences available in GenBank by phylogenetic analysis. Both HA and NA were phylogenetically distinct from those for viruses from outside of North America and from those for viruses recovered from mammals. Four of the H5N1 AI viruses were characterized as low pathogenicity by standard in vivo pathotyping tests. One of the H5N1 viruses, A/MuteSwan/MI/451072-2/06, was shown to replicate to low titers in chickens, turkeys, and ducks. However, transmission of A/MuteSwan/MI/451072-2/06 was more efficient among ducks than among chickens or turkeys based on virus shed. The 50% chicken infectious dose for A/MuteSwan/MI/451072-2/06 and three other wild-waterfowl-origin H5 viruses were also determined and were between 10 5.3 and 107.5 50% egg infective doses. Finally, seven H5 viruses representing different phylogenetic clades were evaluated for their antigenic relatedness by hemagglutination inhibition assay, showing that the antigenic relatedness was largely associated with geographic origin. Overall, the data support the conclusion that North American H5 wild-bird-origin AI viruses are low-pathogenicity wild-bird-adapted viruses and are antigenically and genetically distinct from the highly pathogenic Asian H5N1 virus lineage. Copyright ?? 2007, American Society for Microbiology. All Rights Reserved.

  19. Characterization of low-pathogenicity H5N1 avian influenza viruses from North America

    USGS Publications Warehouse

    Spackman, Erica; Swayne, David E.; Suarez, David L.; Senne, Dennis A.; Pedersen, Janice C.; Killian, Mary Lea; Pasick, John; Handel, Katherine; Somanathan Pillai, Smitha; Lee, Chang-Won; Stallknecht, David; Slemons, Richard; Ip, Hon S.; Deliberto, Tom

    2007-01-01

    Wild-bird surveillance in North America for avian influenza (AI) viruses with a goal of early identification of the Asian H5N1 highly pathogenic AI virus has identified at least six low-pathogenicity H5N1 AI viruses between 2004 and 2006. The hemagglutinin (HA) and neuraminidase (NA) genes from all 6 H5N1 viruses and an additional 38 North American wild-bird-origin H5 subtype and 28 N1 subtype viruses were sequenced and compared with sequences available in GenBank by phylogenetic analysis. Both HA and NA were phylogenetically distinct from those for viruses from outside of North America and from those for viruses recovered from mammals. Four of the H5N1 AI viruses were characterized as low pathogenicity by standard in vivo pathotyping tests. One of the H5N1 viruses, A/MuteSwan/MI/451072-2/06, was shown to replicate to low titers in chickens, turkeys, and ducks. However, transmission of A/MuteSwan/MI/451072-2/06 was more efficient among ducks than among chickens or turkeys based on virus shed. The 50% chicken infectious dose for A/MuteSwan/MI/451072-2/06 and three other wild-waterfowl-origin H5 viruses were also determined and were between 105.3 and 107.5 50% egg infective doses. Finally, seven H5 viruses representing different phylogenetic clades were evaluated for their antigenic relatedness by hemagglutination inhibition assay, showing that the antigenic relatedness was largely associated with geographic origin. Overall, the data support the conclusion that North American H5 wild-bird-origin AI viruses are low-pathogenicity wild-bird-adapted viruses and are antigenically and genetically distinct from the highly pathogenic Asian H5N1 virus lineage.

  20. Role for proteases and HLA-G in the pathogenicity of influenza A viruses.

    PubMed

    Foucault, Marie-Laure; Moules, Vincent; Rosa-Calatrava, Manuel; Riteau, Béatrice

    2011-07-01

    Influenza is one of the most common infectious diseases in humans occurring as seasonal epidemic and sporadic pandemic outbreaks. The ongoing infections of humans with avian H5N1 influenza A viruses (IAV) and the past 2009 pandemic caused by the quadruple human/avian/swine reassortant (H1N1) virus highlights the permanent threat caused by these viruses. This review aims to describe the interaction between the virus and the host, with a particular focus on the role of proteases and HLA-G in the pathogenicity of influenza viruses.

  1. Effect of species, breed and route of virus inoculation on the pathogenicity of H5N1 highly pathogenic influenza (HPAI) viruses in domestic ducks

    PubMed Central

    2013-01-01

    H5N1 highly pathogenic avian influenza (HPAI) viruses continue to be a threat to poultry in many regions of the world. Domestic ducks have been recognized as one of the primary factors in the spread of H5N1 HPAI. In this study we examined the pathogenicity of H5N1 HPAI viruses in different species and breeds of domestic ducks and the effect of route of virus inoculation on the outcome of infection. We determined that the pathogenicity of H5N1 HPAI viruses varies between the two common farmed duck species, with Muscovy ducks (Cairina moschata) presenting more severe disease than various breeds of Anas platyrhynchos var. domestica ducks including Pekin, Mallard-type, Black Runners, Rouen, and Khaki Campbell ducks. We also found that Pekin and Muscovy ducks inoculated with two H5N1 HPAI viruses of different virulence, given by any one of three routes (intranasal, intracloacal, or intraocular), became infected with the viruses. Regardless of the route of inoculation, the outcome of infection was similar for each species but depended on the virulence of the virus used. Muscovy ducks showed more severe clinical signs and higher mortality than the Pekin ducks. In conclusion, domestic ducks are susceptible to H5N1 HPAI virus infection by different routes of exposure, but the presentation of the disease varied by virus strain and duck species. This information helps support the planning and implementation of H5N1 HPAI surveillance and control measures in countries with large domestic duck populations. PMID:23876184

  2. Effect of species, breed and route of virus inoculation on the pathogenicity of H5N1 highly pathogenic influenza (HPAI) viruses in domestic ducks.

    PubMed

    Pantin-Jackwood, Mary; Swayne, David E; Smith, Diane; Shepherd, Eric

    2013-07-22

    H5N1 highly pathogenic avian influenza (HPAI) viruses continue to be a threat to poultry in many regions of the world. Domestic ducks have been recognized as one of the primary factors in the spread of H5N1 HPAI. In this study we examined the pathogenicity of H5N1 HPAI viruses in different species and breeds of domestic ducks and the effect of route of virus inoculation on the outcome of infection. We determined that the pathogenicity of H5N1 HPAI viruses varies between the two common farmed duck species, with Muscovy ducks (Cairina moschata) presenting more severe disease than various breeds of Anas platyrhynchos var. domestica ducks including Pekin, Mallard-type, Black Runners, Rouen, and Khaki Campbell ducks. We also found that Pekin and Muscovy ducks inoculated with two H5N1 HPAI viruses of different virulence, given by any one of three routes (intranasal, intracloacal, or intraocular), became infected with the viruses. Regardless of the route of inoculation, the outcome of infection was similar for each species but depended on the virulence of the virus used. Muscovy ducks showed more severe clinical signs and higher mortality than the Pekin ducks. In conclusion, domestic ducks are susceptible to H5N1 HPAI virus infection by different routes of exposure, but the presentation of the disease varied by virus strain and duck species. This information helps support the planning and implementation of H5N1 HPAI surveillance and control measures in countries with large domestic duck populations.

  3. Neonatal Herpes Simplex Virus Infection.

    PubMed

    James, Scott H; Kimberlin, David W

    2015-09-01

    Herpes simplex virus (HSV) 1 and HSV-2 infections are highly prevalent worldwide and are characterized by establishing lifelong infection with periods of latency interspersed with periodic episodes of reactivation. Acquisition of HSV by an infant during the peripartum or postpartum period results in neonatal HSV disease, a rare but significant infection that can be associated with severe morbidity and mortality, especially if there is dissemination or central nervous system involvement. Diagnostic and therapeutic advances have led to improvements in mortality and, to a lesser extent, neurodevelopmental outcomes, but room exists for further improvement.

  4. Natural infection of turkeys by infectious laryngotracheitis virus.

    PubMed

    Portz, Cristiana; Beltrão, Nilzane; Furian, Thales Quedi; Júnior, Alfredo Bianco; Macagnan, Marisa; Griebeler, Josiane; Lima Rosa, Carlos André Veiga; Colodel, Edson Moleta; Driemeier, David; Back, Alberto; Barth Schatzmayr, Ortrud Monika; Canal, Cláudio Wageck

    2008-09-18

    The infectious laryngotracheitis virus (ILTV) is an important respiratory pathogen of chickens that also infects pheasants and peafowl. Epidemiologically non-related commercial turkey flocks with clinical signs such as tracheitis, swollen sinuses, conjunctivitis and expectoration of bloody mucus were examined for the presence of the virus. Laboratory ILTV detection was performed by virus isolation in embryonated eggs and cell cultures, PCR and sequencing of amplification products, histopathology, indirect immunofluorescence and electron microscopy. One ILTV turkey isolate was also experimentally inoculated into susceptible chickens and turkeys, reproducing a mild respiratory disease. This is the first description of natural infections with ILTV in turkeys.

  5. Natural infection of turkeys by infectious laryngotracheitis virus.

    PubMed

    Portz, Cristiana; Beltrão, Nilzane; Furian, Thales Quedi; Júnior, Alfredo Bianco; Macagnan, Marisa; Griebeler, Josiane; Lima Rosa, Carlos André Veiga; Colodel, Edson Moleta; Driemeier, David; Back, Alberto; Barth Schatzmayr, Ortrud Monika; Canal, Cláudio Wageck

    2008-09-18

    The infectious laryngotracheitis virus (ILTV) is an important respiratory pathogen of chickens that also infects pheasants and peafowl. Epidemiologically non-related commercial turkey flocks with clinical signs such as tracheitis, swollen sinuses, conjunctivitis and expectoration of bloody mucus were examined for the presence of the virus. Laboratory ILTV detection was performed by virus isolation in embryonated eggs and cell cultures, PCR and sequencing of amplification products, histopathology, indirect immunofluorescence and electron microscopy. One ILTV turkey isolate was also experimentally inoculated into susceptible chickens and turkeys, reproducing a mild respiratory disease. This is the first description of natural infections with ILTV in turkeys. PMID:18436397

  6. Effects of different NS genes of avian influenza viruses and amino acid changes on pathogenicity of recombinant A/Puerto Rico/8/34 viruses.

    PubMed

    Kim, Il-Hwan; Kwon, Hyuk-Joon; Lee, Su-Hyung; Kim, Dae-Yong; Kim, Jae-Hong

    2015-01-30

    To examine the effects of the NS1 and NEP genes of avian influenza viruses (AIVs) on pathogenicity in mice, we generated recombinant PR8 viruses containing 3 different NS genes of AIVs. In contrast to the reverse genetics-generated PR8 (rPR8) strain and other recombinant viruses, the recombinant virus rPR8-NS(0028), which contained the NS gene of A/chicken/KBNP-0028/2000 (H9N2) (0028), was non-pathogenic to mice. The novel single mutations of 0028 NS1 to corresponding amino acid of PR8 NS1, G139D and S151T increased the pathogenicity of rPR8-NS(0028). The replacement of the PL motifs (EPEV or RSEV) of pathogenic recombinant viruses with that of 0028 (GSEV) did not reduce the pathogenicity of the viruses. However, a recombinant virus with an EPEV-grafted 0028 NS gene was more pathogenic than rPR8-NS(0028) but less than rPR8. The lower pathogenicity of rPR8-NS(0028) might be associated with the lower virus titer and IFN-β level in the lungs of infected mice, and be attributed to G139, S151 and GSEV-PL motif of NS1 gene of 0028. In conclusion we defined new amino acid residues of NS1 related to mice pathogenicity and the presence of pathogenic NS genes among low pathogenic AIVs may encourage continuous monitoring of their mammalian pathogenicity.

  7. Preference by a virus vector for infected plants is reversed after virus acquisition.

    PubMed

    Rajabaskar, Dheivasigamani; Bosque-Pérez, Nilsa A; Eigenbrode, Sanford D

    2014-06-24

    Pathogens and their vectors can interact either directly or indirectly via their shared hosts, with implications for the persistence and spread of the pathogen in host populations. For example, some plant viruses induce changes in host plants that cause the aphids that carry these viruses to settle preferentially on infected plants. Furthermore, relative preference by the vector for infected plants can change to a preference for noninfected plants after virus acquisition by the vector, as has recently been demonstrated in the wheat-Rhopalosiphum padi-Barley yellow dwarf virus pathosystem. Here we document a similar dynamic in the potato-Myzus persicae (Sulzer)-Potato leaf roll virus (PLRV) pathosystem. Specifically, in a dual choice bioassay, nonviruliferous apterous M. persicae settled preferentially on or near potato plants infected with PLRV relative to noninfected (sham-inoculated) control plants, whereas viruliferous M. persicae (carrying PLRV) preferentially settled on or near sham-inoculated potato plants relative to infected plants. The change in preference after virus acquisition also occurred in response to trapped headspace volatiles, and to synthetic mimics of headspace volatile blends from PLRV-infected and sham-inoculated potato plants. The change in preference we document should promote virus spread by increasing rates of virus acquisition and transmission by the vector. PMID:24269348

  8. Bronchointerstitial pneumonia in guinea pigs following inoculation with H5N1 high pathogenicity avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The H5N1 high pathogenicity avian influenza (HPAI) viruses have caused widespread disease of poultry in Asia, Africa and the Middle East, and sporadic human infections. The guinea pig model has been used to study human H3N2 and H1N1 influenza viruses, but knowledge is lacking on H5N1 HPAI virus inf...

  9. Hepatitis Virus Infections in Poultry.

    PubMed

    Yugo, Danielle M; Hauck, Ruediger; Shivaprasad, H L; Meng, Xiang-Jin

    2016-09-01

    Viral hepatitis in poultry is a complex disease syndrome caused by several viruses belonging to different families including avian hepatitis E virus (HEV), duck hepatitis B virus (DHBV), duck hepatitis A virus (DHAV-1, -2, -3), duck hepatitis virus Types 2 and 3, fowl adenoviruses (FAdV), and turkey hepatitis virus (THV). While these hepatitis viruses share the same target organ, the liver, they each possess unique clinical and biological features. In this article, we aim to review the common and unique features of major poultry hepatitis viruses in an effort to identify the knowledge gaps and aid the prevention and control of poultry viral hepatitis. Avian HEV is an Orthohepevirus B in the family Hepeviridae that naturally infects chickens and consists of three distinct genotypes worldwide. Avian HEV is associated with hepatitis-splenomegaly syndrome or big liver and spleen disease in chickens, although the majority of the infected birds are subclinical. Avihepadnaviruses in the family of Hepadnaviridae have been isolated from ducks, snow geese, white storks, grey herons, cranes, and parrots. DHBV evolved with the host as a noncytopathic form without clinical signs and rarely progressed to chronicity. The outcome for DHBV infection varies by the host's ability to elicit an immune response and is dose and age dependent in ducks, thus mimicking the pathogenesis of human hepatitis B virus (HBV) infections and providing an excellent animal model for human HBV. DHAV is a picornavirus that causes a highly contagious virus infection in ducks with up to 100% flock mortality in ducklings under 6 wk of age, while older birds remain unaffected. The high morbidity and mortality has an economic impact on intensive duck production farming. Duck hepatitis virus Types 2 and 3 are astroviruses in the family of Astroviridae with similarity phylogenetically to turkey astroviruses, implicating the potential for cross-species infections between strains. Duck astrovirus (DAstV) causes

  10. Hepatitis Virus Infections in Poultry.

    PubMed

    Yugo, Danielle M; Hauck, Ruediger; Shivaprasad, H L; Meng, Xiang-Jin

    2016-09-01

    Viral hepatitis in poultry is a complex disease syndrome caused by several viruses belonging to different families including avian hepatitis E virus (HEV), duck hepatitis B virus (DHBV), duck hepatitis A virus (DHAV-1, -2, -3), duck hepatitis virus Types 2 and 3, fowl adenoviruses (FAdV), and turkey hepatitis virus (THV). While these hepatitis viruses share the same target organ, the liver, they each possess unique clinical and biological features. In this article, we aim to review the common and unique features of major poultry hepatitis viruses in an effort to identify the knowledge gaps and aid the prevention and control of poultry viral hepatitis. Avian HEV is an Orthohepevirus B in the family Hepeviridae that naturally infects chickens and consists of three distinct genotypes worldwide. Avian HEV is associated with hepatitis-splenomegaly syndrome or big liver and spleen disease in chickens, although the majority of the infected birds are subclinical. Avihepadnaviruses in the family of Hepadnaviridae have been isolated from ducks, snow geese, white storks, grey herons, cranes, and parrots. DHBV evolved with the host as a noncytopathic form without clinical signs and rarely progressed to chronicity. The outcome for DHBV infection varies by the host's ability to elicit an immune response and is dose and age dependent in ducks, thus mimicking the pathogenesis of human hepatitis B virus (HBV) infections and providing an excellent animal model for human HBV. DHAV is a picornavirus that causes a highly contagious virus infection in ducks with up to 100% flock mortality in ducklings under 6 wk of age, while older birds remain unaffected. The high morbidity and mortality has an economic impact on intensive duck production farming. Duck hepatitis virus Types 2 and 3 are astroviruses in the family of Astroviridae with similarity phylogenetically to turkey astroviruses, implicating the potential for cross-species infections between strains. Duck astrovirus (DAstV) causes

  11. Pathogenicity of the enterococcus in surgical infections.

    PubMed Central

    Barie, P S; Christou, N V; Dellinger, E P; Rout, W R; Stone, H H; Waymack, J P

    1990-01-01

    The enterococcus has been relegated to a position of unimportance in the pathogenesis of surgical infections. However the increasing prevalence and virulence of these bacteria prompt reconsideration of this view, particularly because the surgical patient has become increasingly vulnerable to infectious morbidity due to debility, immunosuppression, and therapy with increasingly potent antibiotics. The enterococcus is a versatile opportunistic nosocomial pathogen, causing such diverse infections as wound, intra-abdominal, and urinary tract infections; catheter-associated infection; suppurative thrombophlebitis; endocarditis; and pneumonia. Although surgical drainage remains the cornerstone of therapy for enterococcal infections involving a discrete focus, in the circumstances typified by the compromised surgical patient, specific antibacterial therapy directed against the enterococcus is warranted. Recent evidence indicates that parenteral antibiotic therapy for enterococcal bacteremia is mandatory and that appropriate therapy clearly reduces the number of deaths. PMID:2198000

  12. Characterization of low-pathogenic H5 subtype influenza viruses from Eurasia: implications for the origin of highly pathogenic H5N1 viruses.

    PubMed

    Duan, L; Campitelli, L; Fan, X H; Leung, Y H C; Vijaykrishna, D; Zhang, J X; Donatelli, I; Delogu, M; Li, K S; Foni, E; Chiapponi, C; Wu, W L; Kai, H; Webster, R G; Shortridge, K F; Peiris, J S M; Smith, Gavin J D; Chen, H; Guan, Y

    2007-07-01

    Highly pathogenic avian influenza (HPAI) H5N1 viruses are now endemic in many Asian countries, resulting in repeated outbreaks in poultry and increased cases of human infection. The immediate precursor of these HPAI viruses is believed to be A/goose/Guangdong/1/96 (Gs/GD)-like H5N1 HPAI viruses first detected in Guangdong, China, in 1996. From 2000 onwards, many novel reassortant H5N1 influenza viruses or genotypes have emerged in southern China. However, precursors of the Gs/GD-like viruses and their subsequent reassortants have not been fully determined. Here we characterize low-pathogenic avian influenza (LPAI) H5 subtype viruses isolated from poultry and migratory birds in southern China and Europe from the 1970s to the 2000s. Phylogenetic analyses revealed that Gs/GD-like virus was likely derived from an LPAI H5 virus in migratory birds. However, its variants arose from multiple reassortments between Gs/GD-like virus and viruses from migratory birds or with those Eurasian viruses isolated in the 1970s. It is of note that unlike HPAI H5N1 viruses, those recent LPAI H5 viruses have not become established in aquatic or terrestrial poultry. Phylogenetic analyses revealed the dynamic nature of the influenza virus gene pool in Eurasia with repeated transmissions between the eastern and western extremities of the continent. The data also show reassortment between influenza viruses from domestic and migratory birds in this region that has contributed to the expanded diversity of the influenza virus gene pool among poultry in Eurasia.

  13. Honey Bee Infecting Lake Sinai Viruses.

    PubMed

    Daughenbaugh, Katie F; Martin, Madison; Brutscher, Laura M; Cavigli, Ian; Garcia, Emma; Lavin, Matt; Flenniken, Michelle L

    2015-06-23

    Honey bees are critical pollinators of important agricultural crops. Recently, high annual losses of honey bee colonies have prompted further investigation of honey bee infecting viruses. To better characterize the recently discovered and very prevalent Lake Sinai virus (LSV) group, we sequenced currently circulating LSVs, performed phylogenetic analysis, and obtained images of LSV2. Sequence analysis resulted in extension of the LSV1 and LSV2 genomes, the first detection of LSV4 in the US, and the discovery of LSV6 and LSV7. We detected LSV1 and LSV2 in the Varroa destructor mite, and determined that a large proportion of LSV2 is found in the honey bee gut, suggesting that vector-mediated, food-associated, and/or fecal-oral routes may be important for LSV dissemination. Pathogen-specific quantitative PCR data, obtained from samples collected during a small-scale monitoring project, revealed that LSV2, LSV1, Black queen cell virus (BQCV), and Nosema ceranae were more abundant in weak colonies than strong colonies within this sample cohort. Together, these results enhance our current understanding of LSVs and illustrate the importance of future studies aimed at investigating the role of LSVs and other pathogens on honey bee health at both the individual and colony levels.

  14. Honey Bee Infecting Lake Sinai Viruses

    PubMed Central

    Daughenbaugh, Katie F.; Martin, Madison; Brutscher, Laura M.; Cavigli, Ian; Garcia, Emma; Lavin, Matt; Flenniken, Michelle L.

    2015-01-01

    Honey bees are critical pollinators of important agricultural crops. Recently, high annual losses of honey bee colonies have prompted further investigation of honey bee infecting viruses. To better characterize the recently discovered and very prevalent Lake Sinai virus (LSV) group, we sequenced currently circulating LSVs, performed phylogenetic analysis, and obtained images of LSV2. Sequence analysis resulted in extension of the LSV1 and LSV2 genomes, the first detection of LSV4 in the US, and the discovery of LSV6 and LSV7. We detected LSV1 and LSV2 in the Varroa destructor mite, and determined that a large proportion of LSV2 is found in the honey bee gut, suggesting that vector-mediated, food-associated, and/or fecal-oral routes may be important for LSV dissemination. Pathogen-specific quantitative PCR data, obtained from samples collected during a small-scale monitoring project, revealed that LSV2, LSV1, Black queen cell virus (BQCV), and Nosema ceranae were more abundant in weak colonies than strong colonies within this sample cohort. Together, these results enhance our current understanding of LSVs and illustrate the importance of future studies aimed at investigating the role of LSVs and other pathogens on honey bee health at both the individual and colony levels. PMID:26110586

  15. Rapidly Expanding Range of Highly Pathogenic Avian Influenza Viruses

    PubMed Central

    Dusek, Robert J.; Spackman, Erica

    2015-01-01

    The movement of highly pathogenic avian influenza (H5N8) virus across Eurasia and into North America and the virus’ propensity to reassort with co-circulating low pathogenicity viruses raise concerns among poultry producers, wildlife biologists, aviculturists, and public health personnel worldwide. Surveillance, modeling, and experimental research will provide the knowledge required for intelligent policy and management decisions. PMID:26079209

  16. Rapidly expanding range of highly pathogenic avian influenza viruses

    USGS Publications Warehouse

    Hall, Jeffrey S.; Dusek, Robert J.; Spackman, Erica

    2015-01-01

    The movement of highly pathogenic avian influenza (H5N8) virus across Eurasia and into North America and the virus’ propensity to reassort with co-circulating low pathogenicity viruses raise concerns among poultry producers, wildlife biologists, aviculturists, and public health personnel worldwide. Surveillance, modeling, and experimental research will provide the knowledge required for intelligent policy and management decisions.

  17. Chikungunya virus infection.

    PubMed

    Sam, I-C; AbuBakar, S

    2006-06-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus which causes epidemic fever, rash and polyarthralgia in Africa and Asia. Two outbreaks have been reported in Malaysia, in Klang, Selangor (1998) and Bagan Panchor, Perak (2006). It is not known if the outbreaks were caused by the recent introduction of CHIKV, or if the virus was already circulating in Malaysia. Seroprevalence studies from the 1960s suggested previous disease activity in certain parts of the country. In Asia, CHIKV is thought to be transmitted by the same mosquitoes as dengue, Aedes aegypti and Ae. albopictus. Due to similarities in clinical presentation with dengue, limited awareness, and a lack of laboratory diagnostic capability, CHIKV is probably often underdiagnosed or misdiagnosed as dengue. Treatment is supportive. The prognosis is generally good, although some patients experience chronic arthritis. With no vaccine or antiviral available, prevention and control depends on surveillance, early identification of outbreaks, and vector control. CHIKV should be borne in mind in sporadic cases, and in patients epidemiologically linked to ongoing local or international outbreaks or endemic areas.

  18. Differential immune response of mallard duck peripheral blood mononuclear cells to two highly pathogenic avian influenza H5N1 viruses with distinct pathogenicity in mallard ducks.

    PubMed

    Cui, Zhu; Hu, Jiao; He, Liang; Li, Qunhui; Gu, Min; Wang, Xiaoquan; Hu, Shunlin; Liu, Huimou; Liu, Wenbo; Liu, Xiaowen; Liu, Xiufan

    2014-02-01

    CK10 and GS10 are two H5N1 highly pathogenic influenza viruses of similar genetic background but differ in their pathogenicity in mallard ducks. CK10 is highly pathogenic whereas GS10 is low pathogenic. In this study, strong inflammatory response in terms of the expression level of several cytokines was observed in mallard duck peripheral blood mononuclear cells (PBMC) infected with CK10 while mild response was triggered in those by GS10 infection. Two remarkable and intense peaks of immune response were induced by CK10 infection within 24 hours (at 8 and 24 hours post infection, respectively) without reducing the virus replication. Our observations indicated that sustained and intense innate immune responses may be central to the high pathogenicity caused by CK10 in ducks.

  19. Pathogenicity of the Korean H5N8 highly pathogenic avian influenza virus in commercial domestic poultry species.

    PubMed

    Lee, Dong-Hun; Kwon, Jung-Hoon; Noh, Jin-Yong; Park, Jae-Keun; Yuk, Seong-Su; Erdene-Ochir, Tseren-Ochir; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Lee, Sang-Won; Song, Chang-Seon

    2016-01-01

    In 2014, the highly pathogenic avian influenza (HPAI) virus H5N8 triggered outbreaks in wild birds and poultry farms in South Korea. In the present study, we investigated the pathogenicity of the H5N8 HPAI virus, belonging to the clade 2.3.4.4, in different species of poultry. For this, we examined clinical signs and viral shedding levels following intranasal inoculation of the virus in 3-week-old commercial layer chickens and quails, 10-week-old Korean native chickens, and 8-week-old Muscovy ducks. Intranasal inoculation with 10(6.0) viruses at 50% egg-infective dose resulted in 100% mortality in the layer chickens (8/8) and quails (4/4), but 60% and 0% deaths in the Korean native chickens (3/5) and Muscovy ducks (0/4), respectively. In addition, transmission of the inoculated virus to contact-exposed birds was evident in all the species used in this study. Based on our results, we conclude that the H5N8 HPAI virus has lower pathogenicity and transmissibility in poultry species compared with previously reported H5N1 HPAI viruses. PMID:26814367

  20. Probiotics in respiratory virus infections.

    PubMed

    Lehtoranta, L; Pitkäranta, A; Korpela, R

    2014-08-01

    Viral respiratory infections are the most common diseases in humans. A large range of etiologic agents challenge the development of efficient therapies. Research suggests that probiotics are able to decrease the risk or duration of respiratory infection symptoms. However, the antiviral mechanisms of probiotics are unclear. The purpose of this paper is to review the current knowledge on the effects of probiotics on respiratory virus infections and to provide insights on the possible antiviral mechanisms of probiotics. A PubMed and Scopus database search was performed up to January 2014 using appropriate search terms on probiotic and respiratory virus infections in cell models, in animal models, and in humans, and reviewed for their relevance. Altogether, thirty-three clinical trials were reviewed. The studies varied highly in study design, outcome measures, probiotics, dose, and matrices used. Twenty-eight trials reported that probiotics had beneficial effects in the outcome of respiratory tract infections (RTIs) and five showed no clear benefit. Only eight studies reported investigating viral etiology from the respiratory tract, and one of these reported a significant decrease in viral load. Based on experimental studies, probiotics may exert antiviral effects directly in probiotic-virus interaction or via stimulation of the immune system. Although probiotics seem to be beneficial in respiratory illnesses, the role of probiotics on specific viruses has not been investigated sufficiently. Due to the lack of confirmatory studies and varied data available, more randomized, double-blind, and placebo-controlled trials in different age populations investigating probiotic dose response, comparing probiotic strains/genera, and elucidating the antiviral effect mechanisms are necessary.

  1. Zika virus infections imported from Brazil to Portugal, 2015.

    PubMed

    Zé-Zé, L; Prata, M B; Teixeira, T; Marques, N; Mondragão, A; Fernandes, R; Saraiva da Cunha, J; Alves, M J

    2016-01-01

    Zika virus is an emerging arbovirus transmitted by Aedes sp. mosquitoes like the Dengue and Chikungunya viruses. Zika virus was until recently considered a mild pathogenic mosquito-borne flavivirus with very few reported benign human infections. In 2007, an epidemic in Micronesia initiated the turnover in the epidemiological history of Zika virus and more recently, the potential association with congenital microcephaly cases in Brazil 2015, still under investigation, led the World Health Organization (WHO) to declare a Public Health Emergency of International Concern on February 1, 2016. Here, we present the clinical and laboratory aspects related to the first four imported human cases of Zika virus in Portugal from Brazil, and alert, regarding the high level of traveling between Portugal and Brazil, and the ongoing expansion of this virus in the Americas, for the threat for Zika virus introduction in Europe and the possible introduction to Madeira Island where Aedes aegypti is present. PMID:27134823

  2. Zika virus infections imported from Brazil to Portugal, 2015.

    PubMed

    Zé-Zé, L; Prata, M B; Teixeira, T; Marques, N; Mondragão, A; Fernandes, R; Saraiva da Cunha, J; Alves, M J

    2016-01-01

    Zika virus is an emerging arbovirus transmitted by Aedes sp. mosquitoes like the Dengue and Chikungunya viruses. Zika virus was until recently considered a mild pathogenic mosquito-borne flavivirus with very few reported benign human infections. In 2007, an epidemic in Micronesia initiated the turnover in the epidemiological history of Zika virus and more recently, the potential association with congenital microcephaly cases in Brazil 2015, still under investigation, led the World Health Organization (WHO) to declare a Public Health Emergency of International Concern on February 1, 2016. Here, we present the clinical and laboratory aspects related to the first four imported human cases of Zika virus in Portugal from Brazil, and alert, regarding the high level of traveling between Portugal and Brazil, and the ongoing expansion of this virus in the Americas, for the threat for Zika virus introduction in Europe and the possible introduction to Madeira Island where Aedes aegypti is present.

  3. Infection of Murine Macrophages by Salmonella enterica Serovar Heidelberg Blocks Murine Norovirus Infectivity and Virus-induced Apoptosis.

    PubMed

    Agnihothram, Sudhakar S; Basco, Maria D S; Mullis, Lisa; Foley, Steven L; Hart, Mark E; Sung, Kidon; Azevedo, Marli P

    2015-01-01

    Gastroenteritis caused by bacterial and viral pathogens constitutes a major public health threat in the United States accounting for 35% of hospitalizations. In particular, Salmonella enterica and noroviruses cause the majority of gastroenteritis infections, with emergence of sporadic outbreaks and incidence of increased infections. Although mechanisms underlying infections by these pathogens have been individually studied, little is known about the mechanisms regulating co-infection by these pathogens. In this study, we utilized RAW 264.7 murine macrophage cells to investigate the mechanisms governing co-infection with S. enterica serovar Heidelberg and murine norovirus (MNV). We demonstrate that infection of RAW 264.7 cells with S. enterica reduces the replication of MNV, in part by blocking virus entry early in the virus life cycle, and inducing antiviral cytokines later in the infection cycle. In particular, bacterial infection prior to, or during MNV infection affected virus entry, whereas MNV entry remained unaltered when the virus infection preceded bacterial invasion. This block in virus entry resulted in reduced virus replication, with the highest impact on replication observed during conditions of co-infection. In contrast, bacterial replication showed a threefold increase in MNV-infected cells, despite the presence of antibiotic in the medium. Most importantly, we present evidence that the infection of MNV-infected macrophages by S. enterica blocked MNV-induced apoptosis, despite allowing efficient virus replication. This apoptosis blockade was evidenced by reduction in DNA fragmentation and absence of poly-ADP ribose polymerase (PARP), caspase 3 and caspase 9 cleavage events. Our study suggests a novel mechanism of pathogenesis whereby initial co-infection with these pathogens could result in prolonged infection by either of these pathogens or both together.

  4. Infection of Murine Macrophages by Salmonella enterica Serovar Heidelberg Blocks Murine Norovirus Infectivity and Virus-induced Apoptosis

    PubMed Central

    Agnihothram, Sudhakar S.; Basco, Maria D. S.; Mullis, Lisa; Foley, Steven L.; Hart, Mark E.; Sung, Kidon; Azevedo, Marli P.

    2015-01-01

    Gastroenteritis caused by bacterial and viral pathogens constitutes a major public health threat in the United States accounting for 35% of hospitalizations. In particular, Salmonella enterica and noroviruses cause the majority of gastroenteritis infections, with emergence of sporadic outbreaks and incidence of increased infections. Although mechanisms underlying infections by these pathogens have been individually studied, little is known about the mechanisms regulating co-infection by these pathogens. In this study, we utilized RAW 264.7 murine macrophage cells to investigate the mechanisms governing co-infection with S. enterica serovar Heidelberg and murine norovirus (MNV). We demonstrate that infection of RAW 264.7 cells with S. enterica reduces the replication of MNV, in part by blocking virus entry early in the virus life cycle, and inducing antiviral cytokines later in the infection cycle. In particular, bacterial infection prior to, or during MNV infection affected virus entry, whereas MNV entry remained unaltered when the virus infection preceded bacterial invasion. This block in virus entry resulted in reduced virus replication, with the highest impact on replication observed during conditions of co-infection. In contrast, bacterial replication showed a threefold increase in MNV-infected cells, despite the presence of antibiotic in the medium. Most importantly, we present evidence that the infection of MNV-infected macrophages by S. enterica blocked MNV-induced apoptosis, despite allowing efficient virus replication. This apoptosis blockade was evidenced by reduction in DNA fragmentation and absence of poly-ADP ribose polymerase (PARP), caspase 3 and caspase 9 cleavage events. Our study suggests a novel mechanism of pathogenesis whereby initial co-infection with these pathogens could result in prolonged infection by either of these pathogens or both together. PMID:26658916

  5. Infection of Murine Macrophages by Salmonella enterica Serovar Heidelberg Blocks Murine Norovirus Infectivity and Virus-induced Apoptosis.

    PubMed

    Agnihothram, Sudhakar S; Basco, Maria D S; Mullis, Lisa; Foley, Steven L; Hart, Mark E; Sung, Kidon; Azevedo, Marli P

    2015-01-01

    Gastroenteritis caused by bacterial and viral pathogens constitutes a major public health threat in the United States accounting for 35% of hospitalizations. In particular, Salmonella enterica and noroviruses cause the majority of gastroenteritis infections, with emergence of sporadic outbreaks and incidence of increased infections. Although mechanisms underlying infections by these pathogens have been individually studied, little is known about the mechanisms regulating co-infection by these pathogens. In this study, we utilized RAW 264.7 murine macrophage cells to investigate the mechanisms governing co-infection with S. enterica serovar Heidelberg and murine norovirus (MNV). We demonstrate that infection of RAW 264.7 cells with S. enterica reduces the replication of MNV, in part by blocking virus entry early in the virus life cycle, and inducing antiviral cytokines later in the infection cycle. In particular, bacterial infection prior to, or during MNV infection affected virus entry, whereas MNV entry remained unaltered when the virus infection preceded bacterial invasion. This block in virus entry resulted in reduced virus replication, with the highest impact on replication observed during conditions of co-infection. In contrast, bacterial replication showed a threefold increase in MNV-infected cells, despite the presence of antibiotic in the medium. Most importantly, we present evidence that the infection of MNV-infected macrophages by S. enterica blocked MNV-induced apoptosis, despite allowing efficient virus replication. This apoptosis blockade was evidenced by reduction in DNA fragmentation and absence of poly-ADP ribose polymerase (PARP), caspase 3 and caspase 9 cleavage events. Our study suggests a novel mechanism of pathogenesis whereby initial co-infection with these pathogens could result in prolonged infection by either of these pathogens or both together. PMID:26658916

  6. Recombinant Vaccinia Virus: Immunization against Multiple Pathogens

    NASA Astrophysics Data System (ADS)

    Perkus, Marion E.; Piccini, Antonia; Lipinskas, Bernard R.; Paoletti, Enzo

    1985-09-01

    The coding sequences for the hepatitis B virus surface antigen, the herpes simplex virus glycoprotein D, and the influenza virus hemagglutinin were inserted into a single vaccinia virus genome. Rabbits inoculated intravenously or intradermally with this polyvalent vaccinia virus recombinant produced antibodies reactive to all three authentic foreign antigens. In addition, the feasibility of multiple rounds of vaccination with recombinant vaccinia virus was demonstrated.

  7. Protection and virus shedding of falcons vaccinated against highly pathogenic avian influenza A virus (H5N1).

    PubMed

    Lierz, Michael; Hafez, Hafez M; Klopfleisch, Robert; Lüschow, Dörte; Prusas, Christine; Teifke, Jens P; Rudolf, Miriam; Grund, Christian; Kalthoff, Donata; Mettenleiter, Thomas; Beer, Martin; Hardert, Timm

    2007-11-01

    Because fatal infections with highly pathogenic avian influenza A (HPAI) virus subtype H5N1 have been reported in birds of prey, we sought to determine detailed information about the birds' susceptibility and protection after vaccination. Ten falcons vaccinated with an inactivated influenza virus (H5N2) vaccine seroconverted. We then challenged 5 vaccinated and 5 nonvaccinated falcons with HPAI (H5N1). All vaccinated birds survived; all unvaccinated birds died within 5 days. For the nonvaccinated birds, histopathologic examination showed tissue degeneration and necrosis, immunohistochemical techniques showed influenza virus antigen in affected tissues, and these birds shed high levels of infectious virus from the oropharynx and cloaca. Vaccinated birds showed no influenza virus antigen in tissues and shed virus at lower titers from the oropharynx only. Vaccination could protect these valuable birds and, through reduced virus shedding, reduce risk for transmission to other avian species and humans.

  8. Drosophila C Virus Systemic Infection Leads to Intestinal Obstruction

    PubMed Central

    Chtarbanova, Stanislava; Lamiable, Olivier; Lee, Kwang-Zin; Galiana, Delphine; Troxler, Laurent; Meignin, Carine; Hetru, Charles; Hoffmann, Jules A.; Daeffler, Laurent

    2014-01-01

    ABSTRACT Drosophila C virus (DCV) is a positive-sense RNA virus belonging to the Dicistroviridae family. This natural pathogen of the model organism Drosophila melanogaster is commonly used to investigate antiviral host defense in flies, which involves both RNA interference and inducible responses. Although lethality is used routinely as a readout for the efficiency of the antiviral immune response in these studies, virus-induced pathologies in flies still are poorly understood. Here, we characterize the pathogenesis associated with systemic DCV infection. Comparison of the transcriptome of flies infected with DCV or two other positive-sense RNA viruses, Flock House virus and Sindbis virus, reveals that DCV infection, unlike those of the other two viruses, represses the expression of a large number of genes. Several of these genes are expressed specifically in the midgut and also are repressed by starvation. We show that systemic DCV infection triggers a nutritional stress in Drosophila which results from intestinal obstruction with the accumulation of peritrophic matrix at the entry of the midgut and the accumulation of the food ingested in the crop, a blind muscular food storage organ. The related virus cricket paralysis virus (CrPV), which efficiently grows in Drosophila, does not trigger this pathology. We show that DCV, but not CrPV, infects the smooth muscles surrounding the crop, causing extensive cytopathology and strongly reducing the rate of contractions. We conclude that the pathogenesis associated with systemic DCV infection results from the tropism of the virus for an important organ within the foregut of dipteran insects, the crop. IMPORTANCE DCV is one of the few identified natural viral pathogens affecting the model organism Drosophila melanogaster. As such, it is an important virus for the deciphering of host-virus interactions in insects. We characterize here the pathogenesis associated with DCV infection in flies and show that it results from the

  9. Greater virulence of highly pathogenic H5N1 influenza virus in cats than in dogs.

    PubMed

    Kim, Heui Man; Park, Eun Hye; Yum, Jung; Kim, Hyun Soo; Seo, Sang Heui

    2015-01-01

    Highly pathogenic H5N1 influenza virus continues to infect animals and humans. We compared the infectivity and pathogenesis of H5N1 virus in domestic cats and dogs to find out which animal is more susceptible to H5N1 influenza virus. When cats and dogs were infected with the H5N1 virus, cats suffered from severe outcomes including death, whereas dogs did not show any mortality. Viruses were shed in the nose and rectum of cats and in the nose of dogs. Viruses were detected in brain, lung, kidney, intestine, liver, and serum in the infected cats, but only in the lung in the infected dogs. Genes encoding inflammatory cytokines and chemokines, Toll-like receptors, and apoptotic factors were more highly expressed in the lungs of cats than in those of dogs. Our results suggest that the intensive monitoring of dogs is necessary to prevent human infection by H5N1 influenza virus, since infected dogs may not show clear clinical signs, in contrast to infected cats.

  10. In vivo replication of pathogenic and attenuated strains of Junin virus in different cell populations of lymphatic tissue.

    PubMed Central

    Laguens, M; Chambó, J G; Laguens, R P

    1983-01-01

    Lymphatic tissue is one of the main sites for replication of Junin virus. To characterize which cells are involved in that replication, the presence of Junin virus in purified populations of macrophages and dendritic cells from the spleens of guinea pigs infected with pathogenic and attenuated strains was investigated by immunofluorescence and intracerebral inoculation into newborn mice. The pathogenic strain was present both in macrophages and in dendritic cells, but the attenuated strain selectively infected dendritic cells. These observations suggest that the pathogenic behavior and replication efficiency of these two strains of Junin virus may be related to a difference in cell targets. Images PMID:6309667

  11. Discrete virus infection model of hepatitis B virus.

    PubMed

    Zhang, Pengfei; Min, Lequan; Pian, Jianwei

    2015-01-01

    In 1996 Nowak and his colleagues proposed a differential equation virus infection model, which has been widely applied in the study for the dynamics of hepatitis B virus (HBV) infection. Biological dynamics may be described more practically by discrete events rather than continuous ones. Using discrete systems to describe biological dynamics should be reasonable. Based on one revised Nowak et al's virus infection model, this study introduces a discrete virus infection model (DVIM). Two equilibriums of this model, E1 and E2, represents infection free and infection persistent, respectively. Similar to the case of the basic virus infection model, this study deduces a basic virus reproductive number R0 independing on the number of total cells of an infected target organ. A proposed theorem proves that if the basic virus reproductive number R0<1 then the virus free equilibrium E1 is locally stable. The DVIM is more reasonable than an abstract discrete susceptible-infected-recovered model (SIRS) whose basic virus reproductive number R0 is relevant to the number of total cells of the infected target organ. As an application, this study models the clinic HBV DNA data of a patient who was accepted via anti-HBV infection therapy with drug lamivudine. The results show that the numerical simulation is good in agreement with the clinic data.

  12. Pathogenicity of reassortant H5N1 highly pathogenic avian influenza viruses in domestic ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pathogenicity of H5N1 highly pathogenic avian influenza (HPAI) viruses in domestic ducks has increased over time. These changes in virulence have been reported with viruses from countries with high population of domestic ducks, including Egypt. In order to understand which viral genes are contri...

  13. Pediatric human immunodeficiency virus infection.

    PubMed Central

    Domachowske, J B

    1996-01-01

    In the past decade, an increase in pediatric human immunodeficiency virus (HIV) infection has had a substantial impact on childhood morbidity and mortality worldwide. The vertical transmission of HIV from mother to infant accounts for the vast majority of these cases. Identification of HIV-infected pregnant women needs to be impoved so that appropriate therapy can be initiated for both mothers and infants. While recent data demonstrate a dramatic decrease in HIV transmission from a subset of women treated with zidovudine during pregnancy, further efforts at reducing transmission are desperately needed. This review focuses on vertically transmitted HIV infection in children, its epidemiology, diagnostic criteria, natural history, and clinical manifestations including infectious and noninfectious complications. An overview of the complex medical management of these children ensues, including the use of antiretroviral therapy. Opportunistic infection prophylaxis is reviewed, along with the important role of other supportive therapies. PMID:8894346

  14. Is There Still Room for Novel Viral Pathogens in Pediatric Respiratory Tract Infections?

    PubMed Central

    Taboada, Blanca; Espinoza, Marco A.; Isa, Pavel; Aponte, Fernando E.; Arias-Ortiz, María A.; Monge-Martínez, Jesús; Rodríguez-Vázquez, Rubén; Díaz-Hernández, Fidel; Zárate-Vidal, Fernando; Wong-Chew, Rosa María; Firo-Reyes, Verónica; del Río-Almendárez, Carlos N.; Gaitán-Meza, Jesús; Villaseñor-Sierra, Alberto; Martínez-Aguilar, Gerardo; Salas-Mier, Ma. del Carmen; Noyola, Daniel E.; Pérez-Gónzalez, Luis F.; López, Susana; Santos-Preciado, José I.; Arias, Carlos F.

    2014-01-01

    Viruses are the most frequent cause of respiratory disease in children. However, despite the advanced diagnostic methods currently in use, in 20 to 50% of respiratory samples a specific pathogen cannot be detected. In this work, we used a metagenomic approach and deep sequencing to examine respiratory samples from children with lower and upper respiratory tract infections that had been previously found negative for 6 bacteria and 15 respiratory viruses by PCR. Nasal washings from 25 children (out of 250) hospitalized with a diagnosis of pneumonia and nasopharyngeal swabs from 46 outpatient children (out of 526) were studied. DNA reads for at least one virus commonly associated to respiratory infections was found in 20 of 25 hospitalized patients, while reads for pathogenic respiratory bacteria were detected in the remaining 5 children. For outpatients, all the samples were pooled into 25 DNA libraries for sequencing. In this case, in 22 of the 25 sequenced libraries at least one respiratory virus was identified, while in all other, but one, pathogenic bacteria were detected. In both patient groups reads for respiratory syncytial virus, coronavirus-OC43, and rhinovirus were identified. In addition, viruses less frequently associated to respiratory infections were also found. Saffold virus was detected in outpatient but not in hospitalized children. Anellovirus, rotavirus, and astrovirus, as well as several animal and plant viruses were detected in both groups. No novel viruses were identified. Adding up the deep sequencing results to the PCR data, 79.2% of 250 hospitalized and 76.6% of 526 ambulatory patients were positive for viruses, and all other children, but one, had pathogenic respiratory bacteria identified. These results suggest that at least in the type of populations studied and with the sampling methods used the odds of finding novel, clinically relevant viruses, in pediatric respiratory infections are low. PMID:25412469

  15. Immunosuppression During Influenza Virus Infection

    PubMed Central

    Kantzler, G. B.; Lauteria, S. F.; Cusumano, C. L.; Lee, J. D.; Ganguly, R.; Waldman, R. H.

    1974-01-01

    The effects of a live attenuated influenza vaccine and subsequent challenge with virulent influenza virus on the delayed hypersensitivity skin test, and the in vitro response of lymphocytes were evaluated. Volunteers were skin tested before and after administration of vaccine or placebo and challenge with PPD (a purified protein derivative of Mycobacterium tuberculosis), candida, mumps, and trichophytin, and their lymphocytes were tested for [3H]thymidine uptake in response to phytohemagglutin. Of eight volunteers who showed evidence of viral replication after administration of the attenuated vaccine, four had a significant diminution in their skin test response, whereas 8 of 13 volunteers infected with virulent influenza virus showed a diminution. Of the 21 volunteers who were infected with either attenuated or virulent influenza virus, 12 showed suppression of their phytohemagglutin response. None of the volunteers who were given placebo vaccine, or who showed no evidence for viral replication after immunization or challenge, had a suppression of their skin test or phytohemagglutin responses. Although most of the infected volunteers demonstrated suppression of their T-cell function, there was no evidence of a similar suppression of B-cell function. PMID:16558116

  16. Pathogenesis of gut virus infection.

    PubMed

    Salim, A F; Phillips, A D; Farthing, M J

    1990-09-01

    In summary, the pathogenesis of many gut virus infections remains uncertain. However, human and animal studies indicate that the majority of gut viruses infect villous enterocytes. Viruses appear to have different affinities for enterocytes at different sites on the villus. Infection of enterocytes leads to cell death, extrusion into the lumen, and villous atrophy when the rate of cell production in the crypts cannot keep pace with the rate of enterocyte loss. This results in a reduced surface area as well as impairment of digestive and absorptive functions. This may also result in a net secretory state. All these changes, along with others such as reduced enzymatic activity and reduced epithelial integrity, may contribute to the induction of an acute but transient malabsorptive diarrhoea which may persist until the digestive/absorptive functions of the enterocyte are restored. However, if colonic compensation is sufficient to handle the increased fluid load, diarrhoea may not be evident. The roles of villous ischaemia, altered countercurrent exchanger of altered immune responses still remain uncertain and require further investigation. PMID:1962725

  17. BK virus infection in human immunodeficiency virus-infected patients.

    PubMed

    Ledesma, J; Muñoz, P; Garcia de Viedma, D; Cabrero, I; Loeches, B; Montilla, P; Gijon, P; Rodriguez-Sanchez, B; Bouza, E

    2012-07-01

    The aim of this study is to evaluate the prevalence of BK virus (BKV) infection in HIV-positive patients receiving highly active antiretroviral therapy (HAART) in our hospital. The presence of BKV was analysed in urine and plasma samples from 78 non-selected HIV-infected patients. Clinical data were recorded using a pre-established protocol. We used a nested PCR to amplify a specific region of the BKV T-large antigen. Positive samples were quantified using real-time PCR. Mean CD4 count in HIV-infected patients was 472 cells/mm3 and median HIV viral load was <50 copies/mL. BKV viraemia was detected in only 1 HIV-positive patient, but 57.7% (45 out of 78) had BKV viruria, which was more common in patients with CD4 counts>500 cells/mm3 (74.3% vs 25.7%; p=0.007). Viruria was present in 21.7% of healthy controls (5 out of 23 samples, p=0.02). All viral loads were low (<100 copies/mL), and we could not find any association between BKV infection and renal or neurological manifestations. We provide an update on the prevalence of BKV in HIV-infected patients treated with HAART. BKV viruria was more common in HIV-infected patients; however, no role for BKV has been demonstrated in this population.

  18. Diagnosis of Respiratory Syncytial Virus Infection

    PubMed Central

    Popow-Kraupp, Therese; Aberle, Judith H

    2011-01-01

    Respiratory syncytial virus (RSV) is one of the most important pathogen causing severe lower respiratory tract infections in all age groups often requiring hospitalization. Rapid laboratory diagnosis of RSV infection significantly decreases the use of antibiotics, additional laboratory testing and is associated with shorter hospitalization periods. The specific diagnosis of RSV infection is based on the detection of virus or viral antigens or virus specific nucleic acid sequences in respiratory secretions. The kind and quality of the clinical specimen exerts a considerable influence on the results of all currently used viral detection assays. Antigen based tests are widely available, easy to perform and the results are available in a short time but their reduced sensitivity and specificity represent a considerable shortcoming. Among the methods available isolation in cell culture was considered the gold standard for the sensitive identification of RSV but is gradually replaced by highly sensitive and specific nucleic acid amplification assays that provide more rapid results. Of these reverse transcription polymerase chain reaction (PCR) was the first and is still the most frequently used nucleic acid-based assay. New methodologies, as for example the real-time PCR methods allow the quantification of viral nucleic acids in the clinical sample. Disadvantages of the nucleic acid based assays are their high costs and their limited standardization. Future research on new methodologies for the diagnosis of viral respiratory tract infections should focus on the development of sensitive, rapid and cost effective test systems allowing the screening for all probable causative agents. In addition varying testing protocols for summer and winter months based on epidemiologic data are needed to direct their practical use. PMID:22262985

  19. [Infections by Arcanobacterium haemolyticum: an emerging pathogen].

    PubMed

    Puerto Alonso, J L; García-Martos, P; Girón González, J A

    2002-09-01

    Arcanobacterium haemolyticum is a grampositive rod wich belonged, until a short time ago, to Corynebacterium genus, and recently classified in a new genus, with only one specie. Human is the main reservoir. It has been isolated from the skin and pharinx of healthy individuals, but also it is cause of infection, specially pharingitis, in children, and chronic cutaneous ulcus, in diabetic patients. Less frequently, it is cause of osteomyelitis, meningitis, pneumonia, abscess, endocarditis and sepsis. Diagnosis is difficult because its double quality: comensal and pathogen. There are not established guidelines for the treatment of these infections, although most of isolated strains are susceptibles to penicillin, erythromicin, clindamycin and tetracycline. High doses of penicillin, with or without gentamicin, it is recommended for the treatment of deep infections. PMID:12420635

  20. Pathogenicity of H3N8 influenza viruses isolated from domestic ducks in chickens with or without Escherichia coli coinfections.

    PubMed

    Pu, Juan; Fan, Yu Lei; Wang, Zhe; Ma, Bo; Brown, Earl G; Liu, Jin Hua

    2012-09-01

    Influenza viruses from domestic aquatic birds can be transmitted to chickens, resulting in continued prevalence of the disease. H3 viruses are one of the most frequently identified subtypes in domestic ducks. Results from our previous serologic study suggested that H3 virus infections potentially exist in chickens with a wide geographical distribution in China. To better understand their pathogenic potential, two H3N8 influenza viruses isolated from domestic ducks were selected for experimental infections in chickens. We found that viral shedding lasted for at least 14 days postinfection for both viruses; however, one virus caused mortality in the chickens when coinfected with Escherichia coli. Sequencing of the viral HA gene isolated from the inoculated chickens revealed two amino acid mutations within the gene. These findings demonstrate the pathogenicity of the H3N8 domestic duck influenza viruses to chickens, highlighting the need for routine epidemiologic investigations of H3 subtype influenza viruses in chicken populations.

  1. Invasive ants carry novel viruses in their new range and form reservoirs for a honeybee pathogen.

    PubMed

    Sébastien, Alexandra; Lester, Philip J; Hall, Richard J; Wang, Jing; Moore, Nicole E; Gruber, Monica A M

    2015-09-01

    When exotic animal species invade new environments they also bring an often unknown microbial diversity, including pathogens. We describe a novel and widely distributed virus in one of the most globally widespread, abundant and damaging invasive ants (Argentine ants, Linepithema humile). The Linepithema humile virus 1 is a dicistrovirus, a viral family including species known to cause widespread arthropod disease. It was detected in samples from Argentina, Australia and New Zealand. Argentine ants in New Zealand were also infected with a strain of Deformed wing virus common to local hymenopteran species, which is a major pathogen widely associated with honeybee mortality. Evidence for active replication of viral RNA was apparent for both viruses. Our results suggest co-introduction and exchange of pathogens within local hymenopteran communities. These viral species may contribute to the collapse of Argentine ant populations and offer new options for the control of a globally widespread invader. PMID:26562935

  2. Invasive ants carry novel viruses in their new range and form reservoirs for a honeybee pathogen.

    PubMed

    Sébastien, Alexandra; Lester, Philip J; Hall, Richard J; Wang, Jing; Moore, Nicole E; Gruber, Monica A M

    2015-09-01

    When exotic animal species invade new environments they also bring an often unknown microbial diversity, including pathogens. We describe a novel and widely distributed virus in one of the most globally widespread, abundant and damaging invasive ants (Argentine ants, Linepithema humile). The Linepithema humile virus 1 is a dicistrovirus, a viral family including species known to cause widespread arthropod disease. It was detected in samples from Argentina, Australia and New Zealand. Argentine ants in New Zealand were also infected with a strain of Deformed wing virus common to local hymenopteran species, which is a major pathogen widely associated with honeybee mortality. Evidence for active replication of viral RNA was apparent for both viruses. Our results suggest co-introduction and exchange of pathogens within local hymenopteran communities. These viral species may contribute to the collapse of Argentine ant populations and offer new options for the control of a globally widespread invader.

  3. Avian Influenza A Virus Infections in Humans

    MedlinePlus

    ... Research Making a Candidate Vaccine Virus Related Links Influenza Types Seasonal Avian Swine Variant Pandemic Other Get ... Submit What's this? Submit Button Past Newsletters Avian Influenza A Virus Infections in Humans Language: English Españ ...

  4. Analysis of resistance and tolerance to virus infection in Drosophila.

    PubMed

    Merkling, Sarah H; van Rij, Ronald P

    2015-07-01

    Host defense to virus infection involves both resistance mechanisms that reduce viral burden and tolerance mechanisms that limit detrimental effects of infection. The fruit fly, Drosophila melanogaster, has emerged as a model for identifying and characterizing the genetic basis of resistance and tolerance. This protocol describes how to analyze host responses to virus infection in Drosophila, and it covers the preparation of virus stocks, experimental inoculation of flies and assessment of host survival and virus production, which are indicative of resistance or tolerance. It also provides guidance on how to account for recently identified confounding factors, including natural genetic variation in the pastrel locus and contamination of fly stocks with persistent viruses and the symbiotic bacterium Wolbachia. Our protocol aims to be accessible to newcomers to the field and, although optimized for virus research using Drosophila, some of the techniques could be adapted to other host organisms and/or other microbial pathogens. Preparation of fly stocks requires ∼1 month, virus stock preparation requires 17-20 d, virus injection and survival assays require 10-15 d and virus titration requires 14 d. PMID:26110714

  5. Analysis of resistance and tolerance to virus infection in Drosophila.

    PubMed

    Merkling, Sarah H; van Rij, Ronald P

    2015-07-01

    Host defense to virus infection involves both resistance mechanisms that reduce viral burden and tolerance mechanisms that limit detrimental effects of infection. The fruit fly, Drosophila melanogaster, has emerged as a model for identifying and characterizing the genetic basis of resistance and tolerance. This protocol describes how to analyze host responses to virus infection in Drosophila, and it covers the preparation of virus stocks, experimental inoculation of flies and assessment of host survival and virus production, which are indicative of resistance or tolerance. It also provides guidance on how to account for recently identified confounding factors, including natural genetic variation in the pastrel locus and contamination of fly stocks with persistent viruses and the symbiotic bacterium Wolbachia. Our protocol aims to be accessible to newcomers to the field and, although optimized for virus research using Drosophila, some of the techniques could be adapted to other host organisms and/or other microbial pathogens. Preparation of fly stocks requires ∼1 month, virus stock preparation requires 17-20 d, virus injection and survival assays require 10-15 d and virus titration requires 14 d.

  6. Newly Emergent Highly Pathogenic H5N9 Subtype Avian Influenza A Virus

    PubMed Central

    Yu, Yang; Wang, Xingbo; Jin, Tao; Wang, Hailong; Si, Weiying; Yang, Hui; Wu, Jiusheng; Yan, Yan; Liu, Guang; Sang, Xiaoyu; Wu, Xiaopeng; Gao, Yuwei; Xia, Xianzhu; Yu, Xinfen; Pan, Jingcao; Gao, George F.

    2015-01-01

    ABSTRACT The novel H7N9 avian influenza virus (AIV) was demonstrated to cause severe human respiratory infections in China. Here, we examined poultry specimens from live bird markets linked to human H7N9 infection in Hangzhou, China. Metagenomic sequencing revealed mixed subtypes (H5, H7, H9, N1, N2, and N9). Subsequently, AIV subtypes H5N9, H7N9, and H9N2 were isolated. Evolutionary analysis showed that the hemagglutinin gene of the novel H5N9 virus originated from A/Muscovy duck/Vietnam/LBM227/2012 (H5N1), which belongs to clade 2.3.2.1. The neuraminidase gene of the novel H5N9 virus originated from human-infective A/Hangzhou/1/2013 (H7N9). The six internal genes were similar to those of other H5N1, H7N9, and H9N2 virus strains. The virus harbored the PQRERRRKR/GL motif characteristic of highly pathogenic AIVs at the HA cleavage site. Receptor-binding experiments demonstrated that the virus binds α-2,3 sialic acid but not α-2,6 sialic acid. Identically, pathogenicity experiments also showed that the virus caused low mortality rates in mice. This newly isolated H5N9 virus is a highly pathogenic reassortant virus originating from H5N1, H7N9, and H9N2 subtypes. Live bird markets represent a potential transmission risk to public health and the poultry industry. IMPORTANCE This investigation confirms that the novel H5N9 subtype avian influenza A virus is a reassortant strain originating from H5N1, H7N9, and H9N2 subtypes and is totally different from the H5N9 viruses reported before. The novel H5N9 virus acquired a highly pathogenic H5 gene and an N9 gene from human-infecting subtype H7N9 but caused low mortality rates in mice. Whether this novel H5N9 virus will cause human infections from its avian host and become a pandemic subtype is not known yet. It is therefore imperative to assess the risk of emergence of this novel reassortant virus with potential transmissibility to public health. PMID:26085150

  7. Prevention of acute otitis media by prophylaxis and treatment of influenza virus infections.

    PubMed

    Glezen, W P

    2000-12-01

    Human experimental challenge studies with influenza virus infection and controlled intervention trials have demonstrated beyond doubt the role of influenza virus infection in the pathogenesis of acute otitis media. Influenza virus infections not only disrupt eustachian tube function, but also impair recovery from infection and facilitate attachment of bacterial pathogens to respiratory epithelial cells. Immunization of young children with either inactivated or live, attenuated influenza vaccine will significantly reduce the incidence of acute otitis media. Early treatment of influenza with antiviral medication will reduce eustachian tube dysfunction that results from influenza virus infection. Influenza produces high morbidity in children that could be averted by universal immunization with attenuated nasal spray vaccine.

  8. Severity of Bovine Tuberculosis Is Associated with Co-Infection with Common Pathogens in Wild Boar

    PubMed Central

    Risco, David; Serrano, Emmanuel; Fernández-Llario, Pedro; Cuesta, Jesús M.; Gonçalves, Pilar; García-Jiménez, Waldo L.; Martínez, Remigio; Cerrato, Rosario; Velarde, Roser; Gómez, Luis; Segalés, Joaquím; Hermoso de Mendoza, Javier

    2014-01-01

    Co-infections with parasites or viruses drive tuberculosis dynamics in humans, but little is known about their effects in other non-human hosts. This work aims to investigate the relationship between Mycobacterium bovis infection and other pathogens in wild boar (Sus scrofa), a recognized reservoir of bovine tuberculosis (bTB) in Mediterranean ecosystems. For this purpose, it has been assessed whether contacts with common concomitant pathogens are associated with the development of severe bTB lesions in 165 wild boar from mid-western Spain. The presence of bTB lesions affecting only one anatomic location (cervical lymph nodes), or more severe patterns affecting more than one location (mainly cervical lymph nodes and lungs), was assessed in infected animals. In addition, the existence of contacts with other pathogens such as porcine circovirus type 2 (PCV2), Aujeszky's disease virus (ADV), swine influenza virus, porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Haemophilus parasuis and Metastrongylus spp, was evaluated by means of serological, microbiological and parasitological techniques. The existence of contacts with a structured community of pathogens in wild boar infected by M. bovis was statistically investigated by null models. Association between this community of pathogens and bTB severity was examined using a Partial Least Squares regression approach. Results showed that adult wild boar infected by M. bovis had contacted with some specific, non-random pathogen combinations. Contact with PCV2, ADV and infection by Metastrongylus spp, was positively correlated to tuberculosis severity. Therefore, measures against these concomitant pathogens such as vaccination or deworming, might be useful in tuberculosis control programmes in the wild boar. However, given the unexpected consequences of altering any community of organisms, further research should evaluate the impact of such measures under

  9. Severity of bovine tuberculosis is associated with co-infection with common pathogens in wild boar.

    PubMed

    Risco, David; Serrano, Emmanuel; Fernández-Llario, Pedro; Cuesta, Jesús M; Gonçalves, Pilar; García-Jiménez, Waldo L; Martínez, Remigio; Cerrato, Rosario; Velarde, Roser; Gómez, Luis; Segalés, Joaquím; Hermoso de Mendoza, Javier

    2014-01-01

    Co-infections with parasites or viruses drive tuberculosis dynamics in humans, but little is known about their effects in other non-human hosts. This work aims to investigate the relationship between Mycobacterium bovis infection and other pathogens in wild boar (Sus scrofa), a recognized reservoir of bovine tuberculosis (bTB) in Mediterranean ecosystems. For this purpose, it has been assessed whether contacts with common concomitant pathogens are associated with the development of severe bTB lesions in 165 wild boar from mid-western Spain. The presence of bTB lesions affecting only one anatomic location (cervical lymph nodes), or more severe patterns affecting more than one location (mainly cervical lymph nodes and lungs), was assessed in infected animals. In addition, the existence of contacts with other pathogens such as porcine circovirus type 2 (PCV2), Aujeszky's disease virus (ADV), swine influenza virus, porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Haemophilus parasuis and Metastrongylus spp, was evaluated by means of serological, microbiological and parasitological techniques. The existence of contacts with a structured community of pathogens in wild boar infected by M. bovis was statistically investigated by null models. Association between this community of pathogens and bTB severity was examined using a Partial Least Squares regression approach. Results showed that adult wild boar infected by M. bovis had contacted with some specific, non-random pathogen combinations. Contact with PCV2, ADV and infection by Metastrongylus spp, was positively correlated to tuberculosis severity. Therefore, measures against these concomitant pathogens such as vaccination or deworming, might be useful in tuberculosis control programmes in the wild boar. However, given the unexpected consequences of altering any community of organisms, further research should evaluate the impact of such measures under

  10. Preservation of Influenza Virus Infectivity by Lyophilization

    PubMed Central

    Beardmore, W. B.; Clark, T. D.; Jones, K. V.

    1968-01-01

    A method of lyophilizing influenza virus in allantoic fluid with retention of high-titer of egg infectivity is described. Five strains of virus were lyophilized, and all were much more stable than fluid virus preparations, retaining 2 to 3 logs of infectivity after storage at 37 C for 60 to 95 days. Statistical analysis of an accelerated storage test by extrapolation of viral degradation indicates that the lyophilized viruses are stable indefinitely at or below room temperature. PMID:5645420

  11. Viruses of Fish: An Overview of Significant Pathogens

    PubMed Central

    Crane, Mark; Hyatt, Alex

    2011-01-01

    The growing global demand for seafood together with the limited capacity of the wild-capture sector to meet this demand has seen the aquaculture industry continue to grow around the world. A vast array of aquatic animal species is farmed in high density in freshwater, brackish and marine systems where they are exposed to new environments and potentially new diseases. On-farm stresses may compromise their ability to combat infection, and farming practices facilitate rapid transmission of disease. Viral pathogens, whether they have been established for decades or whether they are newly emerging as disease threats, are particularly challenging since there are few, if any, efficacious treatments, and the development of effective viral vaccines for delivery in aquatic systems remains elusive. Here, we review a few of the more significant viral pathogens of finfish, including aquabirnaviruses and infectious hematopoietic necrosis virus which have been known since the first half of the 20th century, and more recent viral pathogens, for example betanodaviruses, that have emerged as aquaculture has undergone a dramatic expansion in the past few decades. PMID:22163333

  12. Influenza virus respiratory infection and transmission following ocular inoculation in ferrets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. The ocular surface represents both a potential site of virus replication and a portal of e...

  13. Novel Reassortant H5N6 Influenza A Virus from the Lao People's Democratic Republic Is Highly Pathogenic in Chickens.

    PubMed

    Butler, Jeffrey; Stewart, Cameron R; Layton, Daniel S; Phommachanh, Phouvong; Harper, Jennifer; Payne, Jean; Evans, Ryan M; Valdeter, Stacey; Walker, Som; Harvey, Gemma; Shan, Songhua; Bruce, Matthew P; Rootes, Christina L; Gough, Tamara J; Rohringer, Andreas; Peck, Grantley R; Fardy, Sarah J; Karpala, Adam J; Johnson, Dayna; Wang, Jianning; Douangngeun, Bounlom; Morrissy, Christopher; Wong, Frank Y K; Bean, Andrew G D; Bingham, John; Williams, David T

    2016-01-01

    Avian influenza viruses of H5 subtype can cause highly pathogenic disease in poultry. In March 2014, a new reassortant H5N6 subtype highly pathogenic avian influenza virus emerged in Lao People's Democratic Republic. We have assessed the pathogenicity, pathobiology and immunological responses associated with this virus in chickens. Infection caused moderate to advanced disease in 6 of 6 chickens within 48 h of mucosal inoculation. High virus titers were observed in blood and tissues (kidney, spleen, liver, duodenum, heart, brain and lung) taken at euthanasia. Viral antigen was detected in endothelium, neurons, myocardium, lymphoid tissues and other cell types. Pro-inflammatory cytokines were elevated compared to non-infected birds. Our study confirmed that this new H5N6 reassortant is highly pathogenic, causing disease in chickens similar to that of Asian H5N1 viruses, and demonstrated the ability of such clade 2.3.4-origin H5 viruses to reassort with non-N1 subtype viruses while maintaining a fit and infectious phenotype. Recent detection of influenza H5N6 poultry infections in Lao PDR, China and Viet Nam, as well as six fatal human infections in China, demonstrate that these emergent highly pathogenic H5N6 viruses may be widely established in several countries and represent an emerging threat to poultry and human populations.

  14. Novel Reassortant H5N6 Influenza A Virus from the Lao People's Democratic Republic Is Highly Pathogenic in Chickens.

    PubMed

    Butler, Jeffrey; Stewart, Cameron R; Layton, Daniel S; Phommachanh, Phouvong; Harper, Jennifer; Payne, Jean; Evans, Ryan M; Valdeter, Stacey; Walker, Som; Harvey, Gemma; Shan, Songhua; Bruce, Matthew P; Rootes, Christina L; Gough, Tamara J; Rohringer, Andreas; Peck, Grantley R; Fardy, Sarah J; Karpala, Adam J; Johnson, Dayna; Wang, Jianning; Douangngeun, Bounlom; Morrissy, Christopher; Wong, Frank Y K; Bean, Andrew G D; Bingham, John; Williams, David T

    2016-01-01

    Avian influenza viruses of H5 subtype can cause highly pathogenic disease in poultry. In March 2014, a new reassortant H5N6 subtype highly pathogenic avian influenza virus emerged in Lao People's Democratic Republic. We have assessed the pathogenicity, pathobiology and immunological responses associated with this virus in chickens. Infection caused moderate to advanced disease in 6 of 6 chickens within 48 h of mucosal inoculation. High virus titers were observed in blood and tissues (kidney, spleen, liver, duodenum, heart, brain and lung) taken at euthanasia. Viral antigen was detected in endothelium, neurons, myocardium, lymphoid tissues and other cell types. Pro-inflammatory cytokines were elevated compared to non-infected birds. Our study confirmed that this new H5N6 reassortant is highly pathogenic, causing disease in chickens similar to that of Asian H5N1 viruses, and demonstrated the ability of such clade 2.3.4-origin H5 viruses to reassort with non-N1 subtype viruses while maintaining a fit and infectious phenotype. Recent detection of influenza H5N6 poultry infections in Lao PDR, China and Viet Nam, as well as six fatal human infections in China, demonstrate that these emergent highly pathogenic H5N6 viruses may be widely established in several countries and represent an emerging threat to poultry and human populations. PMID:27631618

  15. Pathogenesis and pathobiology of avian influenza virus infection in birds.

    PubMed

    Pantin-Jackwood, M J; Swayne, D E

    2009-04-01

    Avian influenza (AI) viruses vary in their ability to produce infection, disease and death in different bird species. Based on the pathobiological effect in chickens, AI viruses (AIV) are categorised as low pathogenic (LPAIV) or highly pathogenic (HPAIV). Typically, LPAIV cause asymptomatic infections in wild aquatic birds, but when introduced into domesticated poultry, infections may be asymptomatic or produce clinical signs and lesions reflecting pathophysiological damage to the respiratory, digestive and reproductive systems. The HPAIV have primarily been seen in gallinaceous poultry, producing high morbidity and mortality, and systemic disease with necrosis and inflammation in multiple visceral organs, nervous and cardiovascular systems, and the integument. Although HPAIV have rarely infected domestic waterfowl or wild birds, the Eurasian-African H5N1 HPAIV have evolved over the past decade with the unique capacity to infect and cause disease in domestic ducks and wild birds, producing a range of syndromes including asymptomatic respiratory and digestive tract infections; systemic disease limited to two or three critical organs, usually the brain, heart and pancreas; and severe disseminated infection and death as seen in gallinaceous poultry. Although experimental studies using intranasal inoculation have produced infection in a variety of wild bird species, the inefficiency of contact transmission in some of them, for example, passerines and Columbiformes, suggests they are unlikely to be a reservoir for the viruses, while others such as some wild Anseriformes, can be severely affected and could serve as a dissemination host over intermediate distances.

  16. Grapevine Pathogenic Microorganisms: Understanding Infection Strategies and Host Response Scenarios.

    PubMed

    Armijo, Grace; Schlechter, Rudolf; Agurto, Mario; Muñoz, Daniela; Nuñez, Constanza; Arce-Johnson, Patricio

    2016-01-01

    Grapevine (Vitis vinifera L.) is one of the most important fruit crop worldwide. Commercial cultivars are greatly affected by a large number of pathogenic microorganisms that cause diseases during pre- and/or post-harvest periods, affecting production, processing and export, along with fruit quality. Among the potential threats, we can find bacteria, fungi, oomycete, or viruses with different life cycles, infection mechanisms and evasion strategies. While plant-pathogen interactions are cycles of resistance and susceptibility, resistance traits from natural resources are selected and may be used for breeding purposes and for a sustainable agriculture. In this context, here we summarize some of the most important diseases affecting V. vinifera together with their causal agents. The aim of this work is to bring a comprehensive review of the infection strategies deployed by significant types of pathogens while understanding the host response in both resistance and susceptibility scenarios. New approaches being used to uncover grapevine status during biotic stresses and scientific-based procedures needed to control plant diseases and crop protection are also addressed.

  17. Grapevine Pathogenic Microorganisms: Understanding Infection Strategies and Host Response Scenarios.

    PubMed

    Armijo, Grace; Schlechter, Rudolf; Agurto, Mario; Muñoz, Daniela; Nuñez, Constanza; Arce-Johnson, Patricio

    2016-01-01

    Grapevine (Vitis vinifera L.) is one of the most important fruit crop worldwide. Commercial cultivars are greatly affected by a large number of pathogenic microorganisms that cause diseases during pre- and/or post-harvest periods, affecting production, processing and export, along with fruit quality. Among the potential threats, we can find bacteria, fungi, oomycete, or viruses with different life cycles, infection mechanisms and evasion strategies. While plant-pathogen interactions are cycles of resistance and susceptibility, resistance traits from natural resources are selected and may be used for breeding purposes and for a sustainable agriculture. In this context, here we summarize some of the most important diseases affecting V. vinifera together with their causal agents. The aim of this work is to bring a comprehensive review of the infection strategies deployed by significant types of pathogens while understanding the host response in both resistance and susceptibility scenarios. New approaches being used to uncover grapevine status during biotic stresses and scientific-based procedures needed to control plant diseases and crop protection are also addressed. PMID:27066032

  18. Grapevine Pathogenic Microorganisms: Understanding Infection Strategies and Host Response Scenarios

    PubMed Central

    Armijo, Grace; Schlechter, Rudolf; Agurto, Mario; Muñoz, Daniela; Nuñez, Constanza; Arce-Johnson, Patricio

    2016-01-01

    Grapevine (Vitis vinifera L.) is one of the most important fruit crop worldwide. Commercial cultivars are greatly affected by a large number of pathogenic microorganisms that cause diseases during pre- and/or post-harvest periods, affecting production, processing and export, along with fruit quality. Among the potential threats, we can find bacteria, fungi, oomycete, or viruses with different life cycles, infection mechanisms and evasion strategies. While plant–pathogen interactions are cycles of resistance and susceptibility, resistance traits from natural resources are selected and may be used for breeding purposes and for a sustainable agriculture. In this context, here we summarize some of the most important diseases affecting V. vinifera together with their causal agents. The aim of this work is to bring a comprehensive review of the infection strategies deployed by significant types of pathogens while understanding the host response in both resistance and susceptibility scenarios. New approaches being used to uncover grapevine status during biotic stresses and scientific-based procedures needed to control plant diseases and crop protection are also addressed. PMID:27066032

  19. From cholera to corals: Viruses as drivers of virulence in a major coral bacterial pathogen

    PubMed Central

    Weynberg, Karen D.; Voolstra, Christian R.; Neave, Matthew J.; Buerger, Patrick; van Oppen, Madeleine J. H.

    2015-01-01

    Disease is an increasing threat to reef-building corals. One of the few identified pathogens of coral disease is the bacterium Vibrio coralliilyticus. In Vibrio cholerae, infection by a bacterial virus (bacteriophage) results in the conversion of non-pathogenic strains to pathogenic strains and this can lead to cholera pandemics. Pathogenicity islands encoded in the V. cholerae genome play an important role in pathogenesis. Here we analyse five whole genome sequences of V. coralliilyticus to examine whether virulence is similarly driven by horizontally acquired elements. We demonstrate that bacteriophage genomes encoding toxin genes with homology to those found in pathogenic V. cholerae are integrated in V. coralliilyticus genomes. Virulence factors located on chromosomal pathogenicity islands also exist in some strains of V. coralliilyticus. The presence of these genetic signatures indicates virulence in V. coralliilyticus is driven by prophages and other horizontally acquired elements. Screening for pathogens of coral disease should target conserved regions in these elements. PMID:26644037

  20. Pathogenicity and treatment of Bartonella infections.

    PubMed

    Angelakis, Emmanouil; Raoult, Didier

    2014-07-01

    Bartonella spp. are responsible for emerging and re-emerging diseases around the world. The majority of human infections are caused by Bartonella henselae, Bartonella quintana and Bartonella bacilliformis, although other Bartonella spp. have also been associated with clinical manifestations in humans. The severity of Bartonella infection correlates with the patient's immune status. Clinical manifestations can range from benign and self-limited to severe and life-threatening disease. Clinical conditions associated with Bartonella spp. include local lymphadenopathy, bacteraemia, endocarditis, and tissue colonisation resulting in bacillary angiomatosis and peliosis hepatis. Without treatment, Bartonella infection can cause high mortality. To date, no single treatment is effective for all Bartonella-associated diseases. In the absence of systematic reviews, treatment decisions for Bartonella infections are based on case reports that test a limited number of patients. Antibiotics do not significantly affect the cure rate in patients with Bartonella lymphadenopathy. Patients with Bartonella spp. bacteraemia should be treated with gentamicin and doxycycline, but chloramphenicol has been proposed for the treatment of B. bacilliformis bacteraemia. Gentamicin in combination with doxycycline is considered the best treatment regimen for endocarditis, and erythromycin is the first-line antibiotic therapy for the treatment of angioproliferative lesions. Rifampicin or streptomycin can be used to treat verruga peruana. In this review, we present recent data and recommendations related to the treatment of Bartonella infections based on the pathogenicity of Bartonella spp.

  1. Neuropathology of Zika Virus Infection

    PubMed Central

    Solomon, Isaac H; Milner, Danny A; Folkerth, Rebecca D

    2016-01-01

    Zika virus (ZIKV) is a member of the Flaviviridae family that had been associated only with mild disease prior to the 2015 outbreak in Brazil. A dramatic increase in reported cases of microcephaly and Guillain-Barré syndrome during this time prompted significant research into possible associations with ZIKV and its neurotropic properties. Infection of neural progenitor cells and organoids have been shown to induce apoptosis and dysregulation of growth, and mouse studies have demonstrated viral replication in brain tissue in adults, as well as vertical transmission resulting in embryonic brain abnormalities. Large case series of clinical and radiological findings of congenital ZIKV infection have begun to be published; however, pathology reports have been limited to two case reports and two small case series. Thus far, the findings have largely been restricted to the brain and include diffuse grey and white matter involvement consisting of dystrophic calcifications, gliosis, microglial nodules, neuronophagia, and scattered lymphocytes. Mild chronic villitis was observed in the placental tissue in some cases, and the remaining organs were essentially uninvolved. Larger, systematic studies, including correlation of histological findings with gestational age at the time of maternal infection, will be required to determine the full range of Zika virus-induced abnormalities and to help guide future clinical decision making. PMID:27525286

  2. Within-host competition among the honey bees pathogens Nosema ceranae and Deformed wing virus is asymmetric and to the disadvantage of the virus.

    PubMed

    Doublet, Vincent; Natsopoulou, Myrsini E; Zschiesche, Luise; Paxton, Robert J

    2015-01-01

    Two pathogens co-infecting a common host can either interact positively (facilitation), negatively (competition) or act independently. A correlative study has suggested that two pathogens of the honey bee, Nosema ceranae and Deformed wing virus (DWV), interact negatively within a host (Costa et al., 2011). To test this hypothesis, we sequentially co-infected honey bees with these pathogens in a reciprocally crossed experimental design. Prior establishment in the host ventriculus by N. ceranae inhibited DWV while prior infection by DWV did not impact N. ceranae, highlighting an asymmetry in the competitive interaction between these emerging pathogens.

  3. Persistent Seoul virus infection in Lewis rats.

    PubMed

    Compton, S R; Jacoby, R O; Paturzo, F X; Smith, A L

    2004-07-01

    Mechanistic studies of hantavirus persistence in rodent reservoirs have been limited by the lack of a versatile animal model. This report describes findings from experimental infection of inbred Lewis rats with Seoul virus strain 80-39. Rats inoculated with virus intraperitoneally at 6 days of age became persistently infected without clinical signs. Tissues from Seoul virus-inoculated 6-day-old rats were assessed at 6, 9, and 12 weeks post-inoculation for viral RNA by RT-PCR and in situ hybridization (ISH) and for infectious virus by inoculation of Vero E6 cells. Virus was isolated from lung and kidney of infected rats at 6 weeks and viral RNA was detected in lung, kidney, pancreas, salivary gland, brain, spleen, liver and skin at 6, 9 and 12 weeks. Rats inoculated with Seoul virus intraperitoneally at 10 or 21 days of age became infected without clinical signs but had low to undetectable levels of viral RNA in tissues at 6 weeks post-inoculation. ISH identified vascular smooth muscle and endothelial cells as common sites of persistent infection. Cultured rat smooth muscle cells and to a lesser extent cultured endothelial cells also were susceptible to Seoul virus infection. Pancreatic infection resulted in insulitis with associated hyperglycemia. These studies demonstrate that infant Lewis rats are uniformly susceptible to asymptomatic persistent Seoul virus infection. Additionally, they offer opportunities for correlative in vivo and in vitro study of Seoul virus interactions in host cell types that support persistent infection.

  4. Pathogenicity and Transmissibility of North American Triple Reassortant Swine Influenza A Viruses in Ferrets

    PubMed Central

    Barman, Subrata; Krylov, Petr S.; Fabrizio, Thomas P.; Franks, John; Turner, Jasmine C.; Seiler, Patrick; Wang, David; Rehg, Jerold E.; Erickson, Gene A.; Gramer, Marie; Webster, Robert G.; Webby, Richard J.

    2012-01-01

    North American triple reassortant swine (TRS) influenza A viruses have caused sporadic human infections since 2005, but human-to-human transmission has not been documented. These viruses have six gene segments (PB2, PB1, PA, HA, NP, and NS) closely related to those of the 2009 H1N1 pandemic viruses. Therefore, understanding of these viruses' pathogenicity and transmissibility may help to identify determinants of virulence of the 2009 H1N1 pandemic viruses and to elucidate potential human health threats posed by the TRS viruses. Here we evaluated in a ferret model the pathogenicity and transmissibility of three groups of North American TRS viruses containing swine-like and/or human-like HA and NA gene segments. The study was designed only to detect informative and significant patterns in the transmissibility and pathogenicity of these three groups of viruses. We observed that irrespective of their HA and NA lineages, the TRS viruses were moderately pathogenic in ferrets and grew efficiently in both the upper and lower respiratory tracts. All North American TRS viruses studied were transmitted between ferrets via direct contact. However, their transmissibility by respiratory droplets was related to their HA and NA lineages: TRS viruses with human-like HA and NA were transmitted most efficiently, those with swine-like HA and NA were transmitted minimally or not transmitted, and those with swine-like HA and human-like NA (N2) showed intermediate transmissibility. We conclude that the lineages of HA and NA may play a crucial role in the respiratory droplet transmissibility of these viruses. These findings have important implications for pandemic planning and warrant confirmation. PMID:22829764

  5. Pathogenesis in Eurasian tree sparrows inoculated with H5N1 highly pathogenic avian influenza virus and experimental virus transmission from tree sparrows to chickens.

    PubMed

    Yamamoto, Yu; Nakamura, Kikuyasu; Yamada, Manabu; Mase, Masaji

    2013-06-01

    Small wild birds that routinely enter poultry farms may be possible vectors of Asian lineage H5N1 highly pathogenic avian influenza virus. In this study, we conducted experimental infections using wild-caught Eurasian tree sparrows (Passer montanus) to evaluate their possible epidemiological involvement in virus transmission. When tree sparrows were intranasally inoculated with the virus at a low or high dose, all sparrows excluding euthanatized birds died within 11 days after inoculation. Viruses were frequently isolated from the drinking water, oral swabs, and visceral organs of the sparrows. Immunohistochemical analysis revealed that the virus replicated strongly in the central nervous system, heart, and adrenal gland following primary infection in the upper respiratory tract and a probable subsequent viremic stage. In the contact infection study using virus-inoculated sparrows and untreated contact chickens, more than half of all chickens died from viral infection. In the virus transmission study in which chickens were given drinking water collected from virus-inoculated sparrows, mortality due to viral infection was observed in chickens. Our data suggest that Eurasian tree sparrows could be biological vectors of the H5N1 highly pathogenic avian influenza virus. In addition to frequent virus detection in the drinking water of sparrows, the results of the virus transmission study suggest that waterborne pathways could be important for viral transmission from tree sparrows to poultry.

  6. Hepatitis B virus infection in Indonesia

    PubMed Central

    Yano, Yoshihiko; Utsumi, Takako; Lusida, Maria Inge; Hayashi, Yoshitake

    2015-01-01

    Approximately 240 million people are chronically infected with hepatitis B virus (HBV), 75% of whom reside in Asia. Approximately 600000 of infected patients die each year due to HBV-related diseases or hepatocellular carcinoma (HCC). The endemicity of hepatitis surface antigen in Indonesia is intermediate to high with a geographical difference. The risk of HBV infection is high in hemodialysis (HD) patients, men having sex with men, and health care workers. Occult HBV infection has been detected in various groups such as blood donors, HD patients, and HIV-infected individuals and children. The most common HBV subgenotype in Indonesia is B3 followed by C1. Various novel subgenotypes of HBV have been identified throughout Indonesia, with the novel HBV subgenotypes C6-C16 and D6 being successfully isolated. Although a number of HBV subgenotypes have been discovered in Indonesia, genotype-related pathogenicity has not yet been elucidated in detail. Therefore, genotype-related differences in the prognosis of liver disease and their effects on treatments need to be determined. A previous study conducted in Indonesia revealed that hepatic steatosis was associated with disease progression. Pre-S2 mutations and mutations at C1638T and T1753V in HBV/B3 have been associated with advanced liver diseases including HCC. However, drug resistance to lamivudine, which is prominent in Indonesia, remains obscure. Although the number of studies on HBV in Indonesia has been increasing, adequate databases on HBV infection are limited. We herein provided an overview of the epidemiology and clinical characteristics of HBV infection in Indonesia. PMID:26478663

  7. Hepatitis B virus infection in Indonesia.

    PubMed

    Yano, Yoshihiko; Utsumi, Takako; Lusida, Maria Inge; Hayashi, Yoshitake

    2015-10-14

    Approximately 240 million people are chronically infected with hepatitis B virus (HBV), 75% of whom reside in Asia. Approximately 600000 of infected patients die each year due to HBV-related diseases or hepatocellular carcinoma (HCC). The endemicity of hepatitis surface antigen in Indonesia is intermediate to high with a geographical difference. The risk of HBV infection is high in hemodialysis (HD) patients, men having sex with men, and health care workers. Occult HBV infection has been detected in various groups such as blood donors, HD patients, and HIV-infected individuals and children. The most common HBV subgenotype in Indonesia is B3 followed by C1. Various novel subgenotypes of HBV have been identified throughout Indonesia, with the novel HBV subgenotypes C6-C16 and D6 being successfully isolated. Although a number of HBV subgenotypes have been discovered in Indonesia, genotype-related pathogenicity has not yet been elucidated in detail. Therefore, genotype-related differences in the prognosis of liver disease and their effects on treatments need to be determined. A previous study conducted in Indonesia revealed that hepatic steatosis was associated with disease progression. Pre-S2 mutations and mutations at C1638T and T1753V in HBV/B3 have been associated with advanced liver diseases including HCC. However, drug resistance to lamivudine, which is prominent in Indonesia, remains obscure. Although the number of studies on HBV in Indonesia has been increasing, adequate databases on HBV infection are limited. We herein provided an overview of the epidemiology and clinical characteristics of HBV infection in Indonesia.

  8. Limited Protection from a Pathogenic Chimeric Simian-Human Immunodeficiency Virus Challenge following Immunization with Attenuated Simian Immunodeficiency Virus

    PubMed Central

    Lewis, Mark G.; Yalley-Ogunro, Jake; Greenhouse, Jack J.; Brennan, Terry P.; Jiang, Jennifer Bo; VanCott, Thomas C.; Lu, Yichen; Eddy, Gerald A.; Birx, Deborah L.

    1999-01-01

    Two live attenuated single-deletion mutant simian immunodeficiency virus (SIV) constructs, SIV239Δnef and SIVPBj6.6Δnef, were tested for their abilities to stimulate protective immunity in macaques. During the immunization period the animals were examined for specific immune responses and virus growth. Each construct generated high levels of specific immunity in all of the immunized animals. The SIV239Δnef construct was found to grow to high levels in all immunized animals, with some animals remaining positive for virus isolation and plasma RNA throughout the immunization period. The SIVPBj6.6Δnef was effectively controlled by all of the immunized animals, with virus mostly isolated only during the first few months following immunization and plasma RNA never detected. Following an extended period of immunization of over 80 weeks, the animals were challenged with a pathogenic simian-human immunodeficiency virus (SHIV) isolate, SIV89.6PD, by intravenous injection. All of the SIV239Δnef-immunized animals became infected with the SHIV isolate; two of five animals eventually controlled the challenge and three of five animals, which failed to check the immunizing virus, progressed to disease state before the unvaccinated controls. One of five animals immunized with SIVPBj6.6Δnef totally resisted infection by the challenge virus, while three others limited its growth and the remaining animal became persistently infected and eventually died of a pulmonary thrombus. These data indicate that vaccination with attenuated SIV can protect macaques from disease and in some cases from infection by a divergent SHIV. However, if animals are unable to control the immunizing virus, potential damage that can accelerate the disease course of a pathogenic challenge virus may occur. PMID:9882330

  9. Akabane virus nonstructural protein NSm regulates viral growth and pathogenicity in a mouse model

    PubMed Central

    ISHIHARA, Yukari; SHIODA, Chieko; BANGPHOOMI, Norasuthi; SUGIURA, Keita; SAEKI, Kohei; TSUDA, Shumpei; IWANAGA, Tatsuya; TAKENAKA-UEMA, Akiko; KATO, Kentaro; MURAKAMI, Shin; UCHIDA, Kazuyuki; AKASHI, Hiroomi; HORIMOTO, Taisuke

    2016-01-01

    The biological function of a nonstructural protein, NSm, of Akabane virus (AKAV) is unknown. In this study, we generated a series of NSm deletion mutant viruses by reverse genetics and compared their phenotypes. The mutant in which the NSm coding region was almost completely deleted could not be rescued, suggesting that NSm plays a role in virus replication. We next generated mutant viruses possessing various partial deletions in NSm and identified several regions critical for virus infectivity. All rescued mutant viruses produced smaller plaques and grew inefficiently in cell culture, compared to the wild-type virus. Interestingly, although the pathogenicity of NSm deletion mutant viruses varied in mice depending on their deletion regions and sizes, more than half the mice died following infection with any mutant virus and the dead mice exhibited encephalitis as in wild-type virus-inoculated mice, indicating their neuroinvasiveness. Abundant viral antigens were detected in the brain tissues of dead mice, whereas appreciable antigen was not observed in those of surviving mice, suggesting a correlation between virus growth rate in the brain and neuropathogenicity in mice. We conclude that NSm affects AKAV replication in vitro as well as in vivo and that it may function as a virulence factor. PMID:27181086

  10. Chronic rabies virus infection of cell cultures.

    PubMed

    Wiktor, T J; Clark, H F

    1972-12-01

    Exposure of both mammalian and reptilian cells in tissue culture to different strains of fixed rabies virus resulted in a carrier type of infection. No cytopathic effect was observed in either type of culture; infected cultures could be maintained by cell transfer for unlimited numbers of passages. A consistent pattern of cyclically rising and falling levels of viral infection was observed by fluorescent-antibody staining techniques and by titration of released infectious virus. Resistance to super-infection by vesicular stomatis virus and the production of an interferon-like substance by infected cells indicated that the maintenance of a carrier type of infection may be interferon-mediated. The degree of susceptibility of rabies-infected cells to immunolysis by antirabies antibody in the presence of complement was found to be correlated with the amount of virus maturation occurring by budding through the cell membrane and not with the presence of immunofluorescent antigen in the cytoplasm of infected cells.

  11. Models of dengue virus infection.

    PubMed

    Bente, Dennis A; Rico-Hesse, Rebeca

    2006-01-01

    The need for models of dengue disease has reached a pinnacle as the transmission of this mosquito-borne virus has increased dramatically. Little is known about the mechanisms that lead to dengue fever and its more severe form, dengue hemorrhagic fever; this is owing to the fact that only humans show signs of disease. In the past 5 years, research has better identified the initial target cells of infection, and this has led to the development of models of infection in primary human cell cultures. Mouse-human chimeras, containing these target cells, have also led to progress in developing animal models. These advances should soon end the stalemate in testing antivirals and vaccine preparations that had necessarily been done in incomplete or irrelevant models. PMID:18087566

  12. Zika Virus Infection and Zika Fever: Frequently Asked Questions

    MedlinePlus

    ... Updated: 25 March 2016 ABOUT ZIKA What is Zika virus infection? Zika virus infection is caused by the ... possible to characterize the disease better. How is Zika virus transmitted? Zika virus is transmitted to people through ...

  13. Zika virus and the never-ending story of emerging pathogens and transfusion medicine.

    PubMed

    Marano, Giuseppe; Pupella, Simonetta; Vaglio, Stefania; Liumbruno, Giancarlo M; Grazzini, Giuliano

    2016-03-01

    In the last few years, the transfusion medicine community has been paying special attention to emerging vector-borne diseases transmitted by arboviruses. Zika virus is the latest of these pathogens and is responsible for major outbreaks in Africa, Asia and, more recently, in previously infection-naïve territories of the Pacific area. Many issues regarding this emerging pathogen remain unclear and require further investigation. National health authorities have adopted different prevention strategies. The aim of this review article is to discuss the currently available, though limited, information and the potential impact of this virus on transfusion medicine.

  14. Zika virus and the never-ending story of emerging pathogens and Transfusion Medicine

    PubMed Central

    Marano, Giuseppe; Pupella, Simonetta; Vaglio, Stefania; Liumbruno, Giancarlo M.; Grazzini, Giuliano

    2016-01-01

    In the last few years, the transfusion medicine community has been paying special attention to emerging vector-borne diseases transmitted by arboviruses. Zika virus is the latest of these pathogens and is responsible for major outbreaks in Africa, Asia and, more recently, in previously infection-naïve territories of the Pacific area. Many issues regarding this emerging pathogen remain unclear and require further investigation. National health authorities have adopted different prevention strategies. The aim of this review article is to discuss the currently available, though limited, information and the potential impact of this virus on transfusion medicine. PMID:26674815

  15. Zika virus and the never-ending story of emerging pathogens and transfusion medicine.

    PubMed

    Marano, Giuseppe; Pupella, Simonetta; Vaglio, Stefania; Liumbruno, Giancarlo M; Grazzini, Giuliano

    2016-03-01

    In the last few years, the transfusion medicine community has been paying special attention to emerging vector-borne diseases transmitted by arboviruses. Zika virus is the latest of these pathogens and is responsible for major outbreaks in Africa, Asia and, more recently, in previously infection-naïve territories of the Pacific area. Many issues regarding this emerging pathogen remain unclear and require further investigation. National health authorities have adopted different prevention strategies. The aim of this review article is to discuss the currently available, though limited, information and the potential impact of this virus on transfusion medicine. PMID:26674815

  16. Chronic infection of rodents by Machupo virus.

    PubMed

    Johnson, K M; Mackenzie, R B; Webb, P A; Kuns, M L

    1965-12-17

    Machupo virus, the etiologic agent of human hemorrhagic fever in Bolivia, induced chronic asymptomatic infection in laboratory hamsters and colonized individuals of the peridomestic, wild, South American rodent, Calomys callosus. Viruria was detected for more than 500 and 150 days, respectively, in the two species. Chronic viremia was shown only for Calomys. Virus-neutralizing substances were present in parenterally infected adult animals, but not in animals born to, and in contact with, an infected female. Chronic infection in wild rodents may be an important mechanism in the natural history of Machupo and related virus infections.

  17. Differential Sensitivity of Bat Cells to Infection by Enveloped RNA Viruses: Coronaviruses, Paramyxoviruses, Filoviruses, and Influenza Viruses

    PubMed Central

    Hoffmann, Markus; Müller, Marcel Alexander; Drexler, Jan Felix; Glende, Jörg; Erdt, Meike; Gützkow, Tim; Losemann, Christoph; Binger, Tabea; Deng, Hongkui; Schwegmann-Weßels, Christel; Esser, Karl-Heinz; Drosten, Christian; Herrler, Georg

    2013-01-01

    Bats (Chiroptera) host major human pathogenic viruses including corona-, paramyxo, rhabdo- and filoviruses. We analyzed six different cell lines from either Yinpterochiroptera (including African flying foxes and a rhinolophid bat) or Yangochiroptera (genera Carollia and Tadarida) for susceptibility to infection by different enveloped RNA viruses. None of the cells were sensitive to infection by transmissible gastroenteritis virus (TGEV), a porcine coronavirus, or to infection mediated by the Spike (S) protein of SARS-coronavirus (SARS-CoV) incorporated into pseudotypes based on vesicular stomatitis virus (VSV). The resistance to infection was overcome if cells were transfected to express the respective cellular receptor, porcine aminopeptidase N for TGEV or angiotensin-converting enzyme 2 for SARS-CoV. VSV pseudotypes containing the S proteins of two bat SARS-related CoV (Bg08 and Rp3) were unable to infect any of the six tested bat cell lines. By contrast, viral pseudotypes containing the surface protein GP of Marburg virus from the family Filoviridae infected all six cell lines though at different efficiency. Notably, all cells were sensitive to infection by two paramyxoviruses (Sendai virus and bovine respiratory syncytial virus) and three influenza viruses from different subtypes. These results indicate that bat cells are more resistant to infection by coronaviruses than to infection by paramyxoviruses, filoviruses and influenza viruses. Furthermore, these results show a receptor-dependent restriction of the infection of bat cells by CoV. The implications for the isolation of coronaviruses from bats are discussed. PMID:24023659

  18. Differential sensitivity of bat cells to infection by enveloped RNA viruses: coronaviruses, paramyxoviruses, filoviruses, and influenza viruses.

    PubMed

    Hoffmann, Markus; Müller, Marcel Alexander; Drexler, Jan Felix; Glende, Jörg; Erdt, Meike; Gützkow, Tim; Losemann, Christoph; Binger, Tabea; Deng, Hongkui; Schwegmann-Weßels, Christel; Esser, Karl-Heinz; Drosten, Christian; Herrler, Georg

    2013-01-01

    Bats (Chiroptera) host major human pathogenic viruses including corona-, paramyxo, rhabdo- and filoviruses. We analyzed six different cell lines from either Yinpterochiroptera (including African flying foxes and a rhinolophid bat) or Yangochiroptera (genera Carollia and Tadarida) for susceptibility to infection by different enveloped RNA viruses. None of the cells were sensitive to infection by transmissible gastroenteritis virus (TGEV), a porcine coronavirus, or to infection mediated by the Spike (S) protein of SARS-coronavirus (SARS-CoV) incorporated into pseudotypes based on vesicular stomatitis virus (VSV). The resistance to infection was overcome if cells were transfected to express the respective cellular receptor, porcine aminopeptidase N for TGEV or angiotensin-converting enzyme 2 for SARS-CoV. VSV pseudotypes containing the S proteins of two bat SARS-related CoV (Bg08 and Rp3) were unable to infect any of the six tested bat cell lines. By contrast, viral pseudotypes containing the surface protein GP of Marburg virus from the family Filoviridae infected all six cell lines though at different efficiency. Notably, all cells were sensitive to infection by two paramyxoviruses (Sendai virus and bovine respiratory syncytial virus) and three influenza viruses from different subtypes. These results indicate that bat cells are more resistant to infection by coronaviruses than to infection by paramyxoviruses, filoviruses and influenza viruses. Furthermore, these results show a receptor-dependent restriction of the infection of bat cells by CoV. The implications for the isolation of coronaviruses from bats are discussed. PMID:24023659

  19. Can plant viruses cross the kingdom border and be pathogenic to humans?

    PubMed

    Balique, Fanny; Lecoq, Hervé; Raoult, Didier; Colson, Philippe

    2015-04-01

    Phytoviruses are highly prevalent in plants worldwide, including vegetables and fruits. Humans, and more generally animals, are exposed daily to these viruses, among which several are extremely stable. It is currently accepted that a strict separation exists between plant and vertebrate viruses regarding their host range and pathogenicity, and plant viruses are believed to infect only plants. Accordingly, plant viruses are not considered to present potential pathogenicity to humans and other vertebrates. Notwithstanding these beliefs, there are many examples where phytoviruses circulate and propagate in insect vectors. Several issues are raised here that question if plant viruses might further cross the kingdom barrier to cause diseases in humans. Indeed, there is close relatedness between some plant and animal viruses, and almost identical gene repertoires. Moreover, plant viruses can be detected in non-human mammals and humans samples, and there are evidence of immune responses to plant viruses in invertebrates, non-human vertebrates and humans, and of the entry of plant viruses or their genomes into non-human mammal cells and bodies after experimental exposure. Overall, the question raised here is unresolved, and several data prompt the additional extensive study of the interactions between phytoviruses and non-human mammals and humans, and the potential of these viruses to cause diseases in humans. PMID:25903834

  20. Can Plant Viruses Cross the Kingdom Border and Be Pathogenic to Humans?

    PubMed Central

    Balique, Fanny; Lecoq, Hervé; Raoult, Didier; Colson, Philippe

    2015-01-01

    Phytoviruses are highly prevalent in plants worldwide, including vegetables and fruits. Humans, and more generally animals, are exposed daily to these viruses, among which several are extremely stable. It is currently accepted that a strict separation exists between plant and vertebrate viruses regarding their host range and pathogenicity, and plant viruses are believed to infect only plants. Accordingly, plant viruses are not considered to present potential pathogenicity to humans and other vertebrates. Notwithstanding these beliefs, there are many examples where phytoviruses circulate and propagate in insect vectors. Several issues are raised here that question if plant viruses might further cross the kingdom barrier to cause diseases in humans. Indeed, there is close relatedness between some plant and animal viruses, and almost identical gene repertoires. Moreover, plant viruses can be detected in non-human mammals and humans samples, and there are evidence of immune responses to plant viruses in invertebrates, non-human vertebrates and humans, and of the entry of plant viruses or their genomes into non-human mammal cells and bodies after experimental exposure. Overall, the question raised here is unresolved, and several data prompt the additional extensive study of the interactions between phytoviruses and non-human mammals and humans, and the potential of these viruses to cause diseases in humans. PMID:25903834

  1. Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus.

    PubMed

    Kim, Young-Il; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Lim, Gyo-Jin; Kim, Eun-Ha; Yoon, Sun-Woo; Park, Su-Jin; Kim, Se Mi; Choi, Eun-Ji; Si, Young-Jae; Lee, Ok-Jun; Shim, Woo-Sub; Kim, Si-Wook; Mo, In-Pil; Bae, Yeonji; Lim, Yong Taik; Sung, Moon Hee; Kim, Chul-Joong; Webby, Richard J; Webster, Robert G; Choi, Young Ki

    2014-10-01

    The endemicity of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Asia has led to the generation of reassortant H5 strains with novel gene constellations. A newly emerged HPAI A(H5N8) virus caused poultry outbreaks in the Republic of Korea in 2014. Because newly emerging high-pathogenicity H5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. Here, we characterized A/mallard duck/Korea/W452/2014 (MDk/W452(H5N8)), a representative virus, and evaluated its pathogenic and pandemic potential in various animal models. We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks. Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues. In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses. It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding. Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection. With their potential to become established in ducks, continued circulation of A(H5N8) viruses could alter the genetic evolution of pre-existing avian poultry strains. Overall, detailed virological investigation remains a necessity given the capacity of H5 viruses to evolve to cause human illness with few changes in the viral genome. PMID:26038499

  2. Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus

    PubMed Central

    Kim, Young-Il; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Lim, Gyo-Jin; Kim, Eun-Ha; Yoon, Sun-Woo; Park, Su-Jin; Kim, Se Mi; Choi, Eun-Ji; Si, Young-Jae; Lee, Ok-Jun; Shim, Woo-Sub; Kim, Si-Wook; Mo, In-Pil; Bae, Yeonji; Lim, Yong Taik; Sung, Moon Hee; Kim, Chul-Joong; Webby, Richard J; Webster, Robert G; Choi, Young Ki

    2014-01-01

    The endemicity of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Asia has led to the generation of reassortant H5 strains with novel gene constellations. A newly emerged HPAI A(H5N8) virus caused poultry outbreaks in the Republic of Korea in 2014. Because newly emerging high-pathogenicity H5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. Here, we characterized A/mallard duck/Korea/W452/2014 (MDk/W452(H5N8)), a representative virus, and evaluated its pathogenic and pandemic potential in various animal models. We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks. Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues. In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses. It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding. Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection. With their potential to become established in ducks, continued circulation of A(H5N8) viruses could alter the genetic evolution of pre-existing avian poultry strains. Overall, detailed virological investigation remains a necessity given the capacity of H5 viruses to evolve to cause human illness with few changes in the viral genome. PMID:26038499

  3. Characterization of low-pathogenicity H5 and H7 Korean avian influenza viruses in chickens.

    PubMed

    Lee, D-H; Kwon, J-H; Park, J-K; Lee, Y-N; Yuk, S-S; Lee, J-B; Park, S-Y; Choi, I-S; Song, C-S

    2012-12-01

    To date, all isolated highly pathogenic avian influenza (HPAI) viruses that cause systemic infection with a high mortality rate in poultry species have been known to belong to either the H5 or H7 subtypes. The HPAI viruses may originate because of the insertion of multiple basic amino acids at the cleavage site of the hemagglutinin protein after the low-pathogenic H5 and H7 viruses have been introduced into poultry. In the present study, we investigated the phylogenetic characteristics of the H5 (n = 4) and H7 (n = 3) low-pathogenic avian influenza (LPAI) viruses isolated from wild birds in Korea by using nucleotide sequences of all 8 gene segments of the viral genome. Further, we evaluated the infectivity, transmissibility, and pathogenic potential of these viruses in chickens. Phylogenetic analysis showed that all viruses used in the study clustered in the Eurasian lineage and were similar to the viruses isolated in Asian countries that share the East Asian-Australasian migratory bird flyway. Our H5N2 isolates could not be replicated and transmitted in chickens, but the H7N8 isolates could efficiently be replicated and transmitted to contact-exposure chickens. In addition, because our H7N8 isolates caused watery diarrhea in chickens, these viruses cannot only serve as progenitors of novel HPAI strains but also potentially cause clinical disease in poultry. Although there have been no reports of LPAI mutation to HPAI in these regions, the wild bird surveillance effort should focus on monitoring the introduction and transmission of the HPAI H5N1 and LPAI H5 and H7 viruses.

  4. Influenza A(H5N8) Virus Similar to Strain in Korea Causing Highly Pathogenic Avian Influenza in Germany.

    PubMed

    Harder, Timm; Maurer-Stroh, Sebastian; Pohlmann, Anne; Starick, Elke; Höreth-Böntgen, Detlef; Albrecht, Karin; Pannwitz, Gunter; Teifke, Jens; Gunalan, Vithiagaran; Lee, Raphael T C; Sauter-Louis, Carola; Homeier, Timo; Staubach, Christoph; Wolf, Carola; Strebelow, Günter; Höper, Dirk; Grund, Christian; Conraths, Franz J; Mettenleiter, Thomas C; Beer, Martin

    2015-05-01

    Highly pathogenic avian influenza (H5N8) virus, like the recently described H5N8 strain from Korea, was detected in November 2014 in farmed turkeys and in a healthy common teal (Anas crecca) in northeastern Germany. Infected wild birds possibly introduced this virus. PMID:25897703

  5. Comparative pathogenicity of four strains of Aleutian disease virus for pastel and sapphire mink.

    PubMed

    Hadlow, W J; Race, R E; Kennedy, R C

    1983-09-01

    Information was sought on the comparative pathogenicity of four North American strains (isolates) of Aleutian disease virus for royal pastel (a non-Aleutian genotype) and sapphire (an Aleutian genotype) mink. The four strains (Utah-1, Ontario [Canada], Montana, and Pullman [Washington]), all of mink origin, were inoculated intraperitoneally and intranasally in serial 10-fold dilutions. As indicated by the appearance of specific antibody (counterimmunoelectrophoresis test), all strains readily infected both color phases of mink, and all strains were equally pathogenic for sapphire mink. Not all strains, however, regularly caused Aleutian disease in pastel mink. Infection of pastel mink with the Utah-1 strain invariably led to fatal disease. Infection with the Ontario strain caused fatal disease nearly as often. The Pullman strain, by contrast, almost never caused disease in infected pastel mink. The pathogenicity of the Montana strain for this color phase was between these extremes. These findings emphasize the need to distinguish between infection and disease when mink are exposed to Aleutian disease virus. The distinction has important implications for understanding the natural history of Aleutian disease virus infection in ranch mink.

  6. Comparative pathogenicity of four strains of Aleutian disease virus for pastel and sapphire mink.

    PubMed Central

    Hadlow, W J; Race, R E; Kennedy, R C

    1983-01-01

    Information was sought on the comparative pathogenicity of four North American strains (isolates) of Aleutian disease virus for royal pastel (a non-Aleutian genotype) and sapphire (an Aleutian genotype) mink. The four strains (Utah-1, Ontario [Canada], Montana, and Pullman [Washington]), all of mink origin, were inoculated intraperitoneally and intranasally in serial 10-fold dilutions. As indicated by the appearance of specific antibody (counterimmunoelectrophoresis test), all strains readily infected both color phases of mink, and all strains were equally pathogenic for sapphire mink. Not all strains, however, regularly caused Aleutian disease in pastel mink. Infection of pastel mink with the Utah-1 strain invariably led to fatal disease. Infection with the Ontario strain caused fatal disease nearly as often. The Pullman strain, by contrast, almost never caused disease in infected pastel mink. The pathogenicity of the Montana strain for this color phase was between these extremes. These findings emphasize the need to distinguish between infection and disease when mink are exposed to Aleutian disease virus. The distinction has important implications for understanding the natural history of Aleutian disease virus infection in ranch mink. PMID:6193063

  7. Modeling Zika Virus Infection in Mice.

    PubMed

    Rossi, Shannan L; Vasilakis, Nikos

    2016-07-01

    Understanding the link between Zika virus (ZIKV) infection and microcephaly requires in vivo models of ZIKV infection in pregnant adults and fetuses. Three studies recently generated such mouse models of ZIKV infection, which corroborate previous in vitro evidence linking ZIKV infection and apoptosis induction in neurons and progenitors to microcephaly. PMID:27392219

  8. Modeling Zika Virus Infection in Mice.

    PubMed

    Rossi, Shannan L; Vasilakis, Nikos

    2016-07-01

    Understanding the link between Zika virus (ZIKV) infection and microcephaly requires in vivo models of ZIKV infection in pregnant adults and fetuses. Three studies recently generated such mouse models of ZIKV infection, which corroborate previous in vitro evidence linking ZIKV infection and apoptosis induction in neurons and progenitors to microcephaly.

  9. Systems analysis of West Nile virus infection.

    PubMed

    Suthar, Mehul S; Pulendran, Bali

    2014-06-01

    Emerging and re-emerging mosquito-borne viruses continue to pose a significant threat to human health throughout the world. Over the past decade, West Nile virus (WNV), Dengue virus (DENV), and Chikungunya virus (CHIKV), have caused annual epidemics of virus-induced encephalitis, hemorrhagic fever\\shock syndromes, and arthritis, respectively. Currently, no specific antiviral therapies or vaccines exist for use in humans to combat or prevent these viral infections. Thus, there is a pressing need to define the virus-host interactions that govern immunity and infection outcome. Recent technological breakthroughs in 'omics' resources and high-throughput based assays are beginning to accelerate antiviral drug discovery and improve on current strategies for vaccine design. In this review, we highlight studies with WNV and discuss how traditional and systems biological approaches are being used to rapidly identify novel host targets for therapeutic intervention and develop a deeper conceptual understanding of the host response to virus infection.

  10. Pathogenesis of experimentally induced feline immunodeficiency virus infection in cats.

    PubMed

    Yamamoto, J K; Sparger, E; Ho, E W; Andersen, P R; O'Connor, T P; Mandell, C P; Lowenstine, L; Munn, R; Pedersen, N C

    1988-08-01

    Feline immunodeficiency virus (FIV; formerly, feline T-lymphotropic lentivirus) is a typical lentivirus resembling human and simian immunodeficiency viruses in morphologic features, protein structure, and reverse transcriptase enzyme. It is antigenically dissimilar, however. The virus is tropic for primary and permanent feline T-lymphoblastoid cells and Crandell feline kidney cells. The virus did not grow in other permanent feline non-lymphoblastoid cells that were tested, or in lymphoid and non-lymphoid cells from man, dogs, mice, and sheep. During short-term inoculation studies in cats, the feline immunodeficiency-like syndrome found in nature was not experimentally induced, but a distinct primary phase of infection was observed. Fever and neutropenia were observed 4 to 5 weeks after inoculation; fever lasted several days, and neutropenia persisted from 1 to 9 weeks. Generalized lymphadenopathy that persisted for 2 to 9 months appeared at the same time. Antibodies to FIV appeared 2 weeks after inoculation and then plateaued. Virus was reisolated from the blood of all infected cats within 4 to 5 weeks after inoculation and persisted indefinitely in the face of humoral antibody response. Virus was recovered from blood, plasma, CSF and saliva, but not from colostrum or milk. Contact transmission was achieved slowly in one colony of naturally infected cats, but not between experimentally infected and susceptible specific-pathogen-free cats kept together for periods as long as 4 to 14 months. The infection was transmitted readily, however, by parenteral inoculation with blood, plasma, or infective cell culture fluids. In utero and lactogenic transmission were not observed in kittens born to naturally or experimentally infected queens. Lymphadenopathy observed during the initial stage of FIV infection was ascribed to lymphoid hyperplasia and follicular dysplasia. A myeloproliferative disorder was observed in 1 cat with experimentally induced infection. PMID:2459996

  11. Cellular and humoral mediated immunity and distribution of viral antigen in chickens after infection with a low pathogenic avian influenza virus (H4N6) isolated from wild ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four-week-old commercial chickens were intranasally inoculated with an H4N6 low pathogenicity avian influenza virus (LPAIV) isolated from a duck in Ukraine. Cecum, spleen, lung, and trachea samples were collected from birds from 1 to 21 days post inoculation (dpi) and examined by immunohistochemica...

  12. Experimental biology and pathogenesis of Junin virus infection in animals and man*

    PubMed Central

    Weissenbacher, M. C.; De Guerrero, L. B.; Boxaca, M. C.

    1975-01-01

    A fatal disease resembling Argentine haemorrhagic fever of man has been produced in guinea-pigs and mice by inoculation with Junin virus. Infected guinea-pigs show macroscopic and microscopic haemorrhagic lesions, marked bone marrow changes, decreased leukocytes and platelets in the peripheral blood, and impairment of immunological response. This response permits differentiation between pathogenic (XJ) and attenuated (XJ Cl3) strains. Guinea-pigs inoculated with the XJ Cl3 strain develop an inapparent infection accompanied by slight haematological changes, the appearance of antibody, and protection against challenge with the pathogenic strain. The attenuated strain has been used successfully as an immunizing antigen in 636 human volunteers. Guinea-pigs infected with Tacaribe virus show cross-protection against Junin virus, with the presence of heterologous neutralizing antibodies. Suckling mice infected with Junin virus develop a typical viral encephalitis; the pathogenicity of the virus decreases with increasing age of the mice. Experiments with thymectomized mice and with mice treated with antithymocyte serum suggest that the pathogenicity of Junin virus in this host is related to the integrity of the thymus-dependent immune system. There is evidence that humoral antibodies do not play any role in the development of the encephalitic lesions but rather protect mice against Junin virus infection. A recent serological survey among laboratory workers and inhabitants of the endemic area has demonstrated the presence of inapparent infection with Junin virus. PMID:182401

  13. Attenuated rabies virus activates, while pathogenic rabies virus evades, the host innate immune responses in the central nervous system.

    PubMed

    Wang, Zhi W; Sarmento, Luciana; Wang, Yuhuan; Li, Xia-qing; Dhingra, Vikas; Tseggai, Tesfai; Jiang, Baoming; Fu, Zhen F

    2005-10-01

    Rabies virus (RV) induces encephalomyelitis in humans and animals. However, the pathogenic mechanism of rabies is not fully understood. To investigate the host responses to RV infection, we examined and compared the pathology, particularly the inflammatory responses, and the gene expression profiles in the brains of mice infected with wild-type (wt) virus silver-haired bat RV (SHBRV) or laboratory-adapted virus B2C, using a mouse genomic array (Affymetrix). Extensive inflammatory responses were observed in animals infected with the attenuated RV, but little or no inflammatory responses were found in mice infected with wt RV. Furthermore, attenuated RV induced the expression of the genes involved in the innate immune and antiviral responses, especially those related to the alpha/beta interferon (IFN-alpha/beta) signaling pathways and inflammatory chemokines. For the IFN-alpha/beta signaling pathways, many of the interferon regulatory genes, such as the signal transduction activation transducers and interferon regulatory factors, as well as the effector genes, for example, 2'-5'-oligoadenylate synthetase and myxovirus proteins, are highly induced in mice infected with attenuated RV. However, many of these genes were not up-regulated in mice infected with wt SHBRV. The data obtained by microarray analysis were confirmed by real-time PCR. Together, these data suggest that attenuated RV activates, while pathogenic RV evades, the host innate immune and antiviral responses.

  14. Experimental Infection of Chickens with Intercontinental Reassortant H9N2 Influenza Viruses from Wild Birds.

    PubMed

    Lee, Dong-Hun; Kwon, Jung-Hoon; Park, Jae-Keun; Yuk, Seong-Su; Tseren-Ochir, Erdene-Ochir; Noh, Jin-Yong; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Song, Chang-Seon

    2016-06-01

    The H9N2 subtype of low pathogenic avian influenza (LPAI) virus is the most prevalent LPAI in domestic poultry. We previously reported the natural reassortant H9N2 viruses between North American and Eurasian lineages isolated from wild birds in Korea. These viruses were identified in China and Alaska, providing evidence of intercontinental dispersal. In this study, we evaluated the infectivity, transmissibility, and pathogenic potential of these H9N2 viruses and Eurasian H9N2 virus identified from wild birds using specific-pathogen-free chickens. Three-week-old chickens were infected intranasally. All of these reassortant H9N2 viruses could not be replicated and transmitted in chickens. On the other hand, three out of eight chickens inoculated with the Eurasian H9N2 virus shed detectable levels of virus and showed seroconversion but did not show contact transmission of the virus. Although all reassortant H9N2 viruses could not be replicated and transmitted in chickens, and although there are no reports on reassortant H9N2 virus infection in poultry farms until now, monitoring of reassortant H9N2 viruses should be continued to prepare for the advent and evolution of these viruses. PMID:27309293

  15. Experimental Infection of Chickens with Intercontinental Reassortant H9N2 Influenza Viruses from Wild Birds.

    PubMed

    Lee, Dong-Hun; Kwon, Jung-Hoon; Park, Jae-Keun; Yuk, Seong-Su; Tseren-Ochir, Erdene-Ochir; Noh, Jin-Yong; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Song, Chang-Seon

    2016-06-01

    The H9N2 subtype of low pathogenic avian influenza (LPAI) virus is the most prevalent LPAI in domestic poultry. We previously reported the natural reassortant H9N2 viruses between North American and Eurasian lineages isolated from wild birds in Korea. These viruses were identified in China and Alaska, providing evidence of intercontinental dispersal. In this study, we evaluated the infectivity, transmissibility, and pathogenic potential of these H9N2 viruses and Eurasian H9N2 virus identified from wild birds using specific-pathogen-free chickens. Three-week-old chickens were infected intranasally. All of these reassortant H9N2 viruses could not be replicated and transmitted in chickens. On the other hand, three out of eight chickens inoculated with the Eurasian H9N2 virus shed detectable levels of virus and showed seroconversion but did not show contact transmission of the virus. Although all reassortant H9N2 viruses could not be replicated and transmitted in chickens, and although there are no reports on reassortant H9N2 virus infection in poultry farms until now, monitoring of reassortant H9N2 viruses should be continued to prepare for the advent and evolution of these viruses.

  16. Dissecting the Role of COPI Complexes in Influenza Virus Infection

    PubMed Central

    Sun, Eileen; He, Jiang

    2013-01-01

    As an obligate pathogen, influenza virus requires host cell factors and compartments to mediate productive infection and to produce infectious progeny virus. Recently, several small interfering RNA (siRNA) knockdown screens revealed influenza virus host dependency proteins, all of which identified at least two subunits of the coat protein I (COPI) complex. COPI proteins oligomerize to form coated vesicles that transport contents between the Golgi apparatus and the endoplasmic reticulum, and they have also been reported to mediate endosomal trafficking. However, it remains unclear which steps in the influenza virus infection cycle rely on the COPI complex. Upon systematic dissection of the influenza virus infection cycle, from entry to progeny virion production, we found that prolonged exposure to COPI complex disruption through siRNA depletion resulted in significant defects in virus internalization and trafficking to late endosomes. Acute inhibition of COPI complex recruitment to the Golgi apparatus with pharmacological compounds failed to recapitulate the same entry defects as observed with the COPI-depleted cells but did result in specific decreases in viral membrane protein expression and assembly, leading to defects in progeny virion production. Taken together, our findings suggest that COPI complexes likely function indirectly in influenza virus entry but play direct roles in viral membrane protein expression and assembly. PMID:23255804

  17. Proteins of duck influenza virus responsible for acquisition of pathogenicity in chickens.

    PubMed

    Yamamoto, Naoki; Soda, Kosuke; Sakoda, Yoshihiro; Okamatsu, Masatoshi; Kida, Hiroshi

    2013-05-01

    Influenza virus rgVac1sub-P0 (H5N1) (rgVac1-P0), in which a pair of dibasic amino acid residues was introduced at the cleavage site of the HA of a reassortant of H5N2 and H7N1 viruses of duck origin, was low pathogenic in chickens. Vac1sub-P3 (H5N1) (Vac1-P3) was selected as a highly pathogenic avian influenza virus by 3 consecutive passages in chickens from low pathogenic strain rgVac1-P0. Comparison of amino acid sequences of the virus proteins and experimental infection of chickens with a series of recombinant viruses demonstrated that in addition to the HA, each of the PA, NP, M1, and M2 of Vac1-P3 are responsible for the acquisition of pathogenicity in chickens. These 4 proteins of Vac1-P3 synergistically contributed to efficient virus replication in chickens.

  18. Looking at protists as a source of pathogenic viruses.

    PubMed

    La Scola, Bernard

    2014-12-01

    In the environment, protozoa are predators of bacteria and feed on them. The possibility that some protozoa could be a source of human pathogens is consistent with the discovery that free-living amoebae were the reservoir of Legionella pneumophila, the agent of Legionnaires' disease. Later, while searching for Legionella in the environment using amoeba co-culture, the first giant virus, Acanthamoeba polyphaga mimivirus, was discovered. Since then, many other giant viruses have been isolated, including Marseilleviridae, Pithovirus sibericum, Cafeteria roenbergensis virus and Pandoravirus spp. The methods used to isolate all of these viruses are herein reviewed. By analogy to Legionella, it was originally suspected that these viruses could be human pathogens. After showing by indirect evidence, such as sero-epidemiologic studies, that it was possible for these viruses to be human pathogens, the recent isolation of some of these viruses (belonging to the Mimiviridae and Marseilleviridae families) in humans in the context of pathologic conditions shows that they are opportunistic human pathogens in some instances.

  19. RNA Viruses Infecting Pest Insects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    RNA viruses are viruses whose genetic material is ribonucleic acid (RNA). RNA viruses may be double or single-stranded based on the type of RNA they contain. Single-stranded RNA viruses can be further grouped into negative sense or positive-sense viruses according to the polarity of their RNA. Fur...

  20. Replication and pathogenicity of human immunodeficiency virus type 1 accessory gene mutants in SCID-hu mice.

    PubMed Central

    Aldrovandi, G M; Zack, J A

    1996-01-01

    The functional roles of the human immunodeficiency virus type 1 (HIV-1) accessory genes (nef, vpr, vpu, and vif) are as yet unclear. Using the SCID-hu model system, we have examined the infectivity, replicative capacity, and pathogenicity of strains of the molecular clone HIV-1NL4-3 that contain deletion mutations in these individual accessory genes. We determined that deletion of these genes had differential effects on both infectivity and pathogenicity. Deletion of vpr had little or no effect on viral infectivity, replication, and pathogenicity; however, deletion of vpu or vif had a significant effect on infectivity and moderate effects on pathogenicity. nef-minus strains were the most attenuated in this system, demonstrating significantly lower levels of infectivity and pathogenicity. However, deletion of these individual genes attenuated but did not abrogate the pathogenic properties of HIV-1. Mutant viruses still retained the ability to induce thymocyte depletion to various degrees if implants were infected with higher doses of virus or observed for longer periods of time. The relative contributions of these genes to in vivo pathogenic potential should be taken into consideration when one is contemplating a live attenuated vaccine for HIV-1. PMID:8627668

  1. Infection strategies of enteric pathogenic Escherichia coli

    PubMed Central

    Clements, Abigail; Young, Joanna C.; Constantinou, Nicholas; Frankel, Gad

    2012-01-01

    Enteric Escherichia coli (E. coli) are both natural flora of humans and important pathogens causing significant morbidity and mortality worldwide. Traditionally enteric E. coli have been divided into 6 pathotypes, with further pathotypes often proposed. In this review we suggest expansion of the enteric E. coli into 8 pathotypes to include the emerging pathotypes of adherent invasive E. coli (AIEC) and Shiga-toxin producing enteroaggregative E. coli (STEAEC). The molecular mechanisms that allow enteric E. coli to colonize and cause disease in the human host are examined and for two of the pathotypes that express a type 3 secretion system (T3SS) we discuss the complex interplay between translocated effectors and manipulation of host cell signaling pathways that occurs during infection. PMID:22555463

  2. The genus Aeromonas: taxonomy, pathogenicity, and infection.

    PubMed

    Janda, J Michael; Abbott, Sharon L

    2010-01-01

    Over the past decade, the genus Aeromonas has undergone a number of significant changes of practical importance to clinical microbiologists and scientists alike. In parallel with the molecular revolution in microbiology, several new species have been identified on a phylogenetic basis, and the genome of the type species, A. hydrophila ATCC 7966, has been sequenced. In addition to established disease associations, Aeromonas has been shown to be a significant cause of infections associated with natural disasters (hurricanes, tsunamis, and earthquakes) and has been linked to emerging or new illnesses, including near-drowning events, prostatitis, and hemolytic-uremic syndrome. Despite these achievements, issues still remain regarding the role that Aeromonas plays in bacterial gastroenteritis, the extent to which species identification should be attempted in the clinical laboratory, and laboratory reporting of test results from contaminated body sites containing aeromonads. This article provides an extensive review of these topics, in addition to others, such as taxonomic issues, microbial pathogenicity, and antimicrobial resistance markers.

  3. Increased Pathogenicity of a Reassortant 2009 Pandemic H1N1 Influenza Virus Containing an H5N1 Hemagglutinin▿

    PubMed Central

    Cline, Troy D.; Karlsson, Erik A.; Freiden, Pamela; Seufzer, Bradley J.; Rehg, Jerold E.; Webby, Richard J.; Schultz-Cherry, Stacey

    2011-01-01

    A novel H1N1 influenza virus emerged in 2009 (pH1N1) to become the first influenza pandemic of the 21st century. This virus is now cocirculating with highly pathogenic H5N1 avian influenza viruses in many parts of the world, raising concerns that a reassortment event may lead to highly pathogenic influenza strains with the capacity to infect humans more readily and cause severe disease. To investigate the virulence of pH1N1-H5N1 reassortant viruses, we created pH1N1 (A/California/04/2009) viruses expressing individual genes from an avian H5N1 influenza strain (A/Hong Kong/483/1997). Using several in vitro models of virus replication, we observed increased replication for a reassortant CA/09 virus expressing the hemagglutinin (HA) gene of HK/483 (CA/09-483HA) relative to that of either parental CA/09 virus or reassortant CA/09 expressing other HK/483 genes. This increased replication correlated with enhanced pathogenicity in infected mice similar to that of the parental HK/483 strain. The serial passage of the CA/09 parental virus and the CA/09-483HA virus through primary human lung epithelial cells resulted in increased pathogenicity, suggesting that these viruses easily adapt to humans and become more virulent. In contrast, serial passage attenuated the parental HK/483 virus in vitro and resulted in slightly reduced morbidity in vivo, suggesting that sustained replication in humans attenuates H5N1 avian influenza viruses. Taken together, these data suggest that reassortment between cocirculating human pH1N1 and avian H5N1 influenza strains will result in a virus with the potential for increased pathogenicity in mammals. PMID:21917948

  4. New evidence that Deformed Wing Virus and Black Queen Cell Virus are Multi-host pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The host-range breadth of pathogens can have important consequences for pathogens’ long term evolution and virulence, and play critical roles in the emergence and spread of the new diseases. Black queen cell virus (BQCV) and Deformed wing virus (DWV) are the two most common and prevalent viruses in...

  5. Ebola Virus Infection: What Should Be Known?

    PubMed Central

    Wiwanitkit, Viroj

    2014-01-01

    Ebola virus infection is the present global consideration. This deadly virus can result in a deadly acute febrile hemorrhagic illness. The patient can have several clinical manifestations. As a new emerging infection, the knowledge on this infection is extremely limited. The interesting issues to be discussed include a) the atypical clinical presentation, b) new diagnostic tool, c) new treatment, and d) disease prevention. Those topics will be discussed in this special review. PMID:25535601

  6. Susceptibility of avian species to North American H13 low pathogenic avian influenza viruses.

    PubMed

    Brown, Justin; Poulson, Rebecca; Carter, Deborah; Lebarbenchon, Camille; Pantin-Jackwood, Mary; Spackman, Erica; Shepherd, Eric; Killian, Mary; Stallknecht, David

    2012-12-01

    Gulls are widely recognized reservoirs for low pathogenic avian influenza (LPAI) viruses; however, the subtypes maintained in these populations and/or the transmission mechanisms involved are poorly understood. Although, a wide diversity of influenza viruses have been isolated from gulls, two hemagglutinin subtypes (H13 and H16) are rarely detected in other avian groups, and existing surveillance data suggests they are maintained almost exclusively within gull populations. In order to evaluate the host range of these gull-adapted influenza subtypes and to characterize viral infection in the gull host, we conducted a series of challenge experiments, with multiple North American strains of H13 LPAI virus in ring-billed gulls (Larus delawarensis), mallards (Anas platyrhynchos), chickens (Gallus domesticus), and turkeys (Meleagris gallopavo). The susceptibility to H13 LPAI viruses varied between species and viral strain. Gulls were highly susceptible to H13 LPAI virus infection and excreted virus via the oropharynx and cloaca for several days. The quantity and duration of shedding was similar between the two routes. Turkeys and ducks were resistant to infection with most strains of H13 LPAI virus, but low numbers of inoculated birds were infected after challenge with specific viral strains. Chickens were refractory to infection with all strains of H13 LPAI virus they were challenged with. The experimental results presented herein are consistent with existing surveillance data on H13 LPAI viruses in birds, and indicate that influenza viruses of the H13 subtype are strongly host-adapted to gulls, but rare spill-over into aberrant hosts (i.e., turkeys and ducks) can occur.

  7. Influenza A virus acquires enhanced pathogenicity and transmissibility after serial passages in swine.

    PubMed

    Wei, Kai; Sun, Honglei; Sun, Zhenhong; Sun, Yipeng; Kong, Weili; Pu, Juan; Ma, Guangpeng; Yin, Yanbo; Yang, Hanchun; Guo, Xin; Chang, Kin-Chow; Liu, Jinhua

    2014-10-01

    Genetic and phylogenetic analyses suggest that the pandemic H1N1/2009 virus was derived from well-established swine influenza lineages; however, there is no convincing evidence that the pandemic virus was generated from a direct precursor in pigs. Furthermore, the evolutionary dynamics of influenza virus in pigs have not been well documented. Here, we subjected a recombinant virus (rH1N1) with the same constellation makeup as the pandemic H1N1/2009 virus to nine serial passages in pigs. The severity of infection sequentially increased with each passage. Deep sequencing of viral quasispecies from the ninth passage found five consensus amino acid mutations: PB1 A469T, PA 1129T, NA N329D, NS1 N205K, and NEP T48N. Mutations in the hemagglutinin (HA) protein, however, differed greatly between the upper and lower respiratory tracts. Three representative viral clones with the five consensus mutations were selected for functional evaluation. Relative to the parental virus, the three viral clones showed enhanced replication and polymerase activity in vitro and enhanced replication, pathogenicity, and transmissibility in pigs, guinea pigs, and ferrets in vivo. Specifically, two mutants of rH1N1 (PB1 A469T and a combination of NS1 N205K and NEP T48N) were identified as determinants of transmissibility in guinea pigs. Crucially, one mutant viral clone with the five consensus mutations, which also carried D187E, K211E, and S289N mutations in its HA, additionally was able to infect ferrets by airborne transmission as effectively as the pandemic virus. Our findings demonstrate that influenza virus can acquire viral characteristics that are similar to those of the pandemic virus after limited serial passages in pigs. Importance: We demonstrate here that an engineered reassortant swine influenza virus, with the same gene constellation pattern as the pandemic H1N1/2009 virus and subjected to only nine serial passages in pigs, acquired greatly enhanced virulence and transmissibility

  8. The Synthetic Antiviral Drug Arbidol Inhibits Globally Prevalent Pathogenic Viruses

    PubMed Central

    Pécheur, Eve-Isabelle; Borisevich, Viktoriya; Halfmann, Peter; Morrey, John D.; Smee, Donald F.; Prichard, Mark; Mire, Chad E.; Kawaoka, Yoshihiro; Geisbert, Thomas W.

    2016-01-01

    ABSTRACT Arbidol (ARB) is a synthetic antiviral originally developed to combat influenza viruses. ARB is currently used clinically in several countries but not in North America. We have previously shown that ARB inhibits in vitro hepatitis C virus (HCV) by blocking HCV entry and replication. In this report, we expand the list of viruses that are inhibited by ARB and demonstrate that ARB suppresses in vitro infection of mammalian cells with Ebola virus (EBOV), Tacaribe arenavirus, and human herpesvirus 8 (HHV-8). We also confirm suppression of hepatitis B virus and poliovirus by ARB. ARB inhibited EBOV Zaire Kikwit infection when added before or at the same time as virus infection and was less effective when added 24 h after EBOV infection. Experiments with recombinant vesicular stomatitis virus (VSV) expressing the EBOV Zaire glycoprotein showed that infection was inhibited by ARB at early stages, most likely at the level of viral entry into host cells. ARB inhibited HHV-8 replication to a similar degree as cidofovir. Our data broaden the spectrum of antiviral efficacy of ARB to include globally prevalent viruses that cause significant morbidity and mortality. IMPORTANCE There are many globally prevalent viruses for which there are no licensed vaccines or antiviral medicines. Some of these viruses, such as Ebola virus or members of the arenavirus family, rapidly cause severe hemorrhagic diseases that can be fatal. Other viruses, such as hepatitis B virus or human herpesvirus 8 (HHV-8), establish persistent infections that cause chronic illnesses, including cancer. Thus, finding an affordable, effective, and safe drug that blocks many viruses remains an unmet medical need. The antiviral drug arbidol (ARB), already in clinical use in several countries as an anti-influenza treatment, has been previously shown to suppress the growth of many viruses. In this report, we expand the list of viruses that are blocked by ARB in a laboratory setting to include Ebola virus

  9. Enteric ganglionitis in rhesus macaques infected with simian immunodeficiency virus.

    PubMed

    Orandle, Marlene S; Veazey, Ronald S; Lackner, Andrew A

    2007-06-01

    Gastrointestinal (GI) disease is a debilitating feature of human immunodeficiency virus (HIV) infection that can occur in the absence of histopathological abnormalities or identifiable enteropathogens. However, the mechanisms of GI dysfunction are poorly understood. The present study was undertaken to characterize changes in resident and inflammatory cells in the enteric nervous system (ENS) of macaques during the acute stage of simian immunodeficiency virus (SIV) infection to gain insight into potential pathogenic mechanisms of GI disease. Ganglia from duodenum, ileum, and colon were examined in healthy and acutely infected macaques by using a combination of routine histology, double-label immunofluorescence and in situ hybridization. Evaluation of tissues from infected macaques showed progressive infiltration of myenteric ganglia by CD3+ T cells and IBA1+ macrophages beginning as early as 8 days postinfection. Quantitative image analysis revealed that the severity of myenteric ganglionitis increased with time after SIV infection and, in general, was more severe in ganglia from the small intestine than in ganglia from the colon. Despite an abundance of inflammatory cells in myenteric ganglia during acute infection, the ENS was not a target for virus infection. This study provides evidence that the ENS may be playing a role in the pathogenesis of GI disease and enteropathy in HIV-infected people.

  10. Pathogenicity of virulent infectious bronchitis virus isolate YN on hen ovary and oviduct.

    PubMed

    Zhong, Qi; Hu, Yan-Xin; Jin, Ji-Hui; Zhao, Ye; Zhao, Jing; Zhang, Guo-Zhong

    2016-09-25

    Avian infectious bronchitis is an economically important poultry disease caused by avian infectious bronchitis virus (IBV). IBV isolate YN is a virulent strain, which is genetically similar to most of the prevalent strains in China. In this study, 21-day-old commercial laying hens were infected with IBV strain YN. The damaging effects of the virus on the reproductive organs were evaluated with clinical observations, gross autopsy and histopathological examinations during the 100-day monitoring period post infection. IBV strain YN infection caused a death rate of 40.5%. Microscopic lesions were observed on the ovary post-infection, but were restricted to the acute infection period. The pathological damage to the cystic oviducts were observed throughout the surveillance period. This study provides detailed information on the pathological changes in the hen ovary and oviduct after challenge with IBV strain YN, which could provide a better understanding about the pathogenicity of IBV. PMID:27599936

  11. Stability of the gorilla microbiome despite simian immunodeficiency virus infection.

    PubMed

    Moeller, Andrew H; Peeters, Martine; Ayouba, Ahidjo; Ngole, Eitel Mpoudi; Esteban, Amadine; Hahn, Beatrice H; Ochman, Howard

    2015-02-01

    Simian immunodeficiency viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in faecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. Here, we examine the effects of SIVgor, a close relative of SIVcpz of chimpanzees and HIV-1 of humans, on the gut bacterial communities residing within wild gorillas, revealing that gorilla gut microbiomes are exceptionally robust to SIV infection. In contrast to the microbiomes of HIV-1-infected humans and SIVcpz-infected chimpanzees, SIVgor-infected gorilla microbiomes exhibit neither rises in the frequencies of opportunistic pathogens nor elevated rates of microbial turnover within individual hosts. Regardless of SIV infection status, gorilla microbiomes assort into enterotypes, one of which is compositionally analogous to those identified in humans and chimpanzees. The other gorilla enterotype appears specialized for a leaf-based diet and is enriched in environmentally derived bacterial genera. We hypothesize that the acquisition of this gorilla-specific enterotype was enabled by lowered immune system control over the composition of the microbiome. Our results indicate differences between the pathology of SIVgor and SIVcpz/HIV-1 infections, demonstrating the utility of investigating host microbial ecology as a means for studying disease in wild primates of high conservation priority.

  12. Modeling inoculum dose dependent patterns of acute virus infections.

    PubMed

    Li, Yan; Handel, Andreas

    2014-04-21

    Inoculum dose, i.e. the number of pathogens at the beginning of an infection, often affects key aspects of pathogen and immune response dynamics. These in turn determine clinically relevant outcomes, such as morbidity and mortality. Despite the general recognition that inoculum dose is an important component of infection outcomes, we currently do not understand its impact in much detail. This study is intended to start filling this knowledge gap by analyzing inoculum dependent patterns of viral load dynamics in acute infections. Using experimental data for adenovirus and infectious bronchitis virus infections as examples, we demonstrate inoculum dose dependent patterns of virus dynamics. We analyze the data with the help of mathematical models to investigate what mechanisms can reproduce the patterns observed in experimental data. We find that models including components of both the innate and adaptive immune response are needed to reproduce the patterns found in the data. We further analyze which types of innate or adaptive immune response models agree with observed data. One interesting finding is that only models for the adaptive immune response that contain growth terms partially independent of viral load can properly reproduce observed patterns. This agrees with the idea that an antigen-independent, programmed response is part of the adaptive response. Our analysis provides useful insights into the types of model structures that are required to properly reproduce observed virus dynamics for varying inoculum doses. We suggest that such models should be taken as basis for future models of acute viral infections.

  13. Detection and diagnosis of rice-infecting viruses

    PubMed Central

    Uehara-Ichiki, Tamaki; Shiba, Takuya; Matsukura, Keiichiro; Ueno, Takanori; Hirae, Masahiro; Sasaya, Takahide

    2013-01-01

    Rice-infecting viruses have caused serious damage to rice production in Asian, American, and African countries, where about 30 rice viruses and diseases have been reported. To control these diseases, developing accurate, quick methods to detect and diagnose the viruses in the host plants and any insect vectors of the viruses is very important. Based on an antigen–antibody reaction, serological methods such as latex agglutination reaction and enzyme-linked immunosorbent assay have advanced to detect viral particles or major proteins derived from viruses. They aid in forecasting disease and surveying disease spread and are widely used for virus detection at plant protection stations and research laboratories. From the early 2000s, based on sequence information for the target virus, several other methods such as reverse transcription-polymerase chain reaction (RT-PCR) and reverse transcription-loop-mediated isothermal amplification have been developed that are sensitive, rapid, and able to differentiate closely related viruses. Recent techniques such as real-time RT-PCR can be used to quantify the pathogen in target samples and monitor population dynamics of a virus, and metagenomic analyses using next-generation sequencing and microarrays show potential for use in the diagnosis of rice diseases. PMID:24130554

  14. Naturally occurring, nonregressing canine oral papillomavirus infection: host immunity, virus characterization, and experimental infection.

    PubMed

    Nicholls, P K; Klaunberg, B A; Moore, R A; Santos, E B; Parry, N R; Gough, G W; Stanley, M A

    1999-12-20

    Papillomaviruses occasionally cause severe, nonregressing or recurrent infections in their human and animal hosts. The mechanisms underlying these atypical infections are not known. Canine oral papillomavirus (COPV) typically regresses spontaneously and is an important model of mucosal human papillomavirus infections. A severe, naturally occurring, nonregressing COPV infection provided an opportunity to investigate some aspects of viral pathogenicity and host immunity. In this case, the papillomas proved refractory to surgical and medical treatments, including autogenous vaccination and vaccination with capsid (L1) virus-like particles. High levels of induced anti-L1 antibodies appeared to have no effect on the infection. The papillomas spread to oesophageal mucosa, perioral haired skin, and remote cutaneous sites. Isolation of COPV from the animal and sequencing of several regions of the viral genome showed no differences to the COPV prototype. Experimental infection of beagle dogs with this viral isolate resulted in the uncomplicated development and regression of oral warts within the usual period, indicating that the virus was not an unusual pathogenic variant. These findings support the hypothesis that the recurrent lesions seen in some human papillomavirus infections, such as recurrent laryngeal papillomatosis, are associated with specific defects in host immunity rather than variations in viral pathogenicity. PMID:10600607

  15. Cell autonomous regulation of herpes and influenza virus infection by the circadian clock.

    PubMed

    Edgar, Rachel S; Stangherlin, Alessandra; Nagy, Andras D; Nicoll, Michael P; Efstathiou, Stacey; O'Neill, John S; Reddy, Akhilesh B

    2016-09-01

    Viruses are intracellular pathogens that hijack host cell machinery and resources to replicate. Rather than being constant, host physiology is rhythmic, undergoing circadian (∼24 h) oscillations in many virus-relevant pathways, but whether daily rhythms impact on viral replication is unknown. We find that the time of day of host infection regulates virus progression in live mice and individual cells. Furthermore, we demonstrate that herpes and influenza A virus infections are enhanced when host circadian rhythms are abolished by disrupting the key clock gene transcription factor Bmal1. Intracellular trafficking, biosynthetic processes, protein synthesis, and chromatin assembly all contribute to circadian regulation of virus infection. Moreover, herpesviruses differentially target components of the molecular circadian clockwork. Our work demonstrates that viruses exploit the clockwork for their own gain and that the clock represents a novel target for modulating viral replication that extends beyond any single family of these ubiquitous pathogens.

  16. Molecular characterization of double-stranded RNA virus in Trichomonas vaginalis Egyptian isolates and its association with pathogenicity.

    PubMed

    El-Gayar, Eman K; Mokhtar, Amira B; Hassan, Wael A

    2016-10-01

    Trichomoniasis is a common human sexually transmitted infection caused by Trichomonas vaginalis. The parasite can be infected with double-stranded RNA viruses (TVV). This viral infection may have important implications on trichomonal virulence and disease pathogenesis. This study aimed to determine the prevalence of T. vaginalis virus among isolates obtained from infected (symptomatic and asymptomatic) women in Ismailia City, Egypt, and to correlate the virus-infected isolates with the clinical manifestations of patients. In addition, the pathogenicity of TVV infected isolates on mice was also evaluated. T. vaginalis isolates were obtained from symptomatic and asymptomatic female patients followed by axenic cultivation in Diamond's TYM medium. The presence of T. vaginalis virus was determined from total extraction of nucleic acids (DNA-RNA) followed by reverse transcriptase-PCR. Representative samples were inoculated intraperitoneally in female albino/BALB mice to assess the pathogenicity of different isolates. A total of 110 women were examined; 40 (36.3 %) samples were positive for T. vaginalis infection. Of these 40 isolates, 8 (20 %) were infected by TVV. Five isolates contained TVV-2 virus species, and the remaining three isolates were infected withTVV-4 variant. A significant association was found between the presence of TVV and particular clinical manifestations of trichomoniasis. Experimental mice infection showed varying degrees of pathogenicity. This is the first report on T. vaginalis infection by TVV in Egypt. The strong association detected between TVV and particular clinical features of trichomoniasis and also the degree of pathogenicity in experimentally infected mice may indicate a possible clinical significance of TVV infection of T. vaginalis isolates. PMID:27316695

  17. Hendra Virus Infection in Dog, Australia, 2013

    PubMed Central

    Gabor, Melinda; Poe, Ian; Neale, Kristie; Chaffey, Kim; Finlaison, Deborah S.; Gu, Xingnian; Hick, Paul M.; Read, Andrew J.; Wright, Therese; Middleton, Deborah

    2015-01-01

    Hendra virus occasionally causes severe disease in horses and humans. In Australia in 2013, infection was detected in a dog that had been in contact with an infected horse. Abnormalities and viral RNA were found in the dog’s kidney, brain, lymph nodes, spleen, and liver. Dogs should be kept away from infected horses. PMID:26583697

  18. Hendra Virus Infection in Dog, Australia, 2013.

    PubMed

    Kirkland, Peter D; Gabor, Melinda; Poe, Ian; Neale, Kristie; Chaffey, Kim; Finlaison, Deborah S; Gu, Xingnian; Hick, Paul M; Read, Andrew J; Wright, Therese; Middleton, Deborah

    2015-12-01

    Hendra virus occasionally causes severe disease in horses and humans. In Australia in 2013, infection was detected in a dog that had been in contact with an infected horse. Abnormalities and viral RNA were found in the dog's kidney, brain, lymph nodes, spleen, and liver. Dogs should be kept away from infected horses.

  19. Glomerulonephritis secondary to Barmah Forest virus infection.

    PubMed

    Katz, I A; Hale, G E; Hudson, B J; Ibels, L S; Eckstein, R P; Dermott, P L

    1997-07-01

    Clinical infection with Barmah Forest virus (BFV) is becoming increasingly recognised with serological testing. We report the first case of glomerulonephritis after BFV infection. The patient required diuretic and antihypertensive therapy, but made an almost complete recovery. BFV infection should be considered in the differential diagnosis of glomerulonephritis. PMID:9236755

  20. Innate immune response to arenaviral infection: a focus on the highly pathogenic New World hemorrhagic arenaviruses

    PubMed Central

    Koma, Takaaki; Huang, Cheng; Kolokoltsova, Olga A; Brasier, Allan R; Paessler, Slobodan

    2013-01-01

    Arenaviruses are enveloped, negative-stranded RNA viruses that belong to the family Arenaviridae. This diverse family can be further classified into OW (Old World) and NW (New World) arenaviruses based on their antigenicity, phylogeny, and geographical distribution. Many of the NW arenaviruses are highly pathogenic viruses that cause systemic human infections characterized by hemorrhagic fever and/or neurological manifestations, constituting public health problems in their endemic regions. NW arenavirus infection induces a variety of host innate immune responses, which could contribute to the viral pathogenesis and/or influence the final outcome of virus infection in vitro as well as in vivo. On the other hand, NW arenaviruses have also developed several strategies to counteract the host innate immune response. We will review current knowledge regarding the interplay between the host innate immune response and NW arenavirus infection in vitro and in vivo, with emphasis on viral-encoded proteins and their effect on the type I interferon response. PMID:24075870

  1. Characterization of a highly pathogenic avian influenza H5N1 virus isolated from an ostrich.

    PubMed

    Yang, Penghui; Dongmei; Wang, Cheng; Tang, Chong; Xing, Li; Luo, Deyan; Zhan, Zhongpeng; Duan, Yueqiang; Jia, Weihong; Peng, Daxin; Liu, Xiufan; Wang, Xiliang

    2010-06-11

    The continued spread of a highly pathogenic avian influenza (HPAI) H5N1 virus among poultry and wild birds has posed a potential threat to human public health. An influenza pandemic happens, when a new subtype that has not previously circulated in humans emerges. Almost all of the influenza pandemics in history have originated from avian influenza viruses (AIV). Birds are significant reservoirs of influenza viruses. In the present study, we performed a survey of avian influenza virus in ostriches and H5N1 virus (A/Ostrich/SuZhou/097/03, China097) was isolated. This H5N1 virus is highly pathogenic to both chickens and mice. It is also able to replicate in the lungs of, and to cause death in, BALB/c mice following intranasal administration. It forms plaques in chicken embryo fibroblast (CEF) cells in the absence of trypsin. The hemagglutinin (HA) gene of the virus is genetically similar to A/Goose/Guangdong/1/96(H5N1) and belongs to clade 0. The HA sequence contains multiple basic amino acids adjacent to the cleavage site, a motif associated with HPAI viruses. More importantly, the existence of H5N1 isolates in ostriches highlights the potential threat of wild bird infections to veterinary and public health. PMID:20497905

  2. Natural and Experimental Infection of Caenorhabditis Nematodes by Novel Viruses Related to Nodaviruses

    PubMed Central

    Wu, Guang; Nuez, Isabelle; Bélicard, Tony; Jiang, Yanfang; Zhao, Guoyan; Franz, Carl J.; Goldstein, Leonard D.; Sanroman, Mabel; Miska, Eric A.; Wang, David

    2011-01-01

    An ideal model system to study antiviral immunity and host-pathogen co-evolution would combine a genetically tractable small animal with a virus capable of naturally infecting the host organism. The use of C. elegans as a model to define host-viral interactions has been limited by the lack of viruses known to infect nematodes. From wild isolates of C. elegans and C. briggsae with unusual morphological phenotypes in intestinal cells, we identified two novel RNA viruses distantly related to known nodaviruses, one infecting specifically C. elegans (Orsay virus), the other C. briggsae (Santeuil virus). Bleaching of embryos cured infected cultures demonstrating that the viruses are neither stably integrated in the host genome nor transmitted vertically. 0.2 µm filtrates of the infected cultures could infect cured animals. Infected animals continuously maintained viral infection for 6 mo (∼50 generations), demonstrating that natural cycles of horizontal virus transmission were faithfully recapitulated in laboratory culture. In addition to infecting the natural C. elegans isolate, Orsay virus readily infected laboratory C. elegans mutants defective in RNAi and yielded higher levels of viral RNA and infection symptoms as compared to infection of the corresponding wild-type N2 strain. These results demonstrated a clear role for RNAi in the defense against this virus. Furthermore, different wild C. elegans isolates displayed differential susceptibility to infection by Orsay virus, thereby affording genetic approaches to defining antiviral loci. This discovery establishes a bona fide viral infection system to explore the natural ecology of nematodes, host-pathogen co-evolution, the evolution of small RNA responses, and innate antiviral mechanisms. PMID:21283608

  3. Natural and experimental infection of Caenorhabditis nematodes by novel viruses related to nodaviruses.

    PubMed

    Félix, Marie-Anne; Ashe, Alyson; Piffaretti, Joséphine; Wu, Guang; Nuez, Isabelle; Bélicard, Tony; Jiang, Yanfang; Zhao, Guoyan; Franz, Carl J; Goldstein, Leonard D; Sanroman, Mabel; Miska, Eric A; Wang, David

    2011-01-25

    An ideal model system to study antiviral immunity and host-pathogen co-evolution would combine a genetically tractable small animal with a virus capable of naturally infecting the host organism. The use of C. elegans as a model to define host-viral interactions has been limited by the lack of viruses known to infect nematodes. From wild isolates of C. elegans and C. briggsae with unusual morphological phenotypes in intestinal cells, we identified two novel RNA viruses distantly related to known nodaviruses, one infecting specifically C. elegans (Orsay virus), the other C. briggsae (Santeuil virus). Bleaching of embryos cured infected cultures demonstrating that the viruses are neither stably integrated in the host genome nor transmitted vertically. 0.2 µm filtrates of the infected cultures could infect cured animals. Infected animals continuously maintained viral infection for 6 mo (∼50 generations), demonstrating that natural cycles of horizontal virus transmission were faithfully recapitulated in laboratory culture. In addition to infecting the natural C. elegans isolate, Orsay virus readily infected laboratory C. elegans mutants defective in RNAi and yielded higher levels of viral RNA and infection symptoms as compared to infection of the corresponding wild-type N2 strain. These results demonstrated a clear role for RNAi in the defense against this virus. Furthermore, different wild C. elegans isolates displayed differential susceptibility to infection by Orsay virus, thereby affording genetic approaches to defining antiviral loci. This discovery establishes a bona fide viral infection system to explore the natural ecology of nematodes, host-pathogen co-evolution, the evolution of small RNA responses, and innate antiviral mechanisms.

  4. Evidence of Apeu Virus Infection in Wild Monkeys, Brazilian Amazon.

    PubMed

    Oliveira, Danilo B; Luiz, Ana Paula Moreira Franco; Fagundes, Alexandre; Pinto, Carla Amaral; Bonjardim, Cláudio A; Trindade, Giliane S; Kroon, Erna G; Abrahão, Jônatas S; Ferreira, Paulo C P

    2016-03-01

    Orthobunyaviruses are arboviruses in which at least 30 members are human pathogens. The members of group C orthobunyaviruses were first isolated in the Brazilian Amazon in 1950, since that time little information is accumulated about ecology and the medical impact of these virus groups in Brazil. Herein, we describe the evidence of Apeu virus (APEUV; an Orthobunyavirus member) infection in wild monkeys from the Brazilian Amazon forest. APEUV was detected by using a neutralizing antibody in serum and its RNA, suggesting past and acute infection of Amazonian monkeys by this virus. These results altogether represent an important contribution of orthobunyavirus ecology in the Amazon and an update about recent circulation and risk for humans with expansion of the cities to Amazon forest.

  5. Pathogens penetrating the central nervous system: infection pathways and the cellular and molecular mechanisms of invasion.

    PubMed

    Dando, Samantha J; Mackay-Sim, Alan; Norton, Robert; Currie, Bart J; St John, James A; Ekberg, Jenny A K; Batzloff, Michael; Ulett, Glen C; Beacham, Ifor R

    2014-10-01

    The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis.

  6. Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

    PubMed Central

    Dando, Samantha J.; Mackay-Sim, Alan; Norton, Robert; Currie, Bart J.; St. John, James A.; Ekberg, Jenny A. K.; Batzloff, Michael

    2014-01-01

    SUMMARY The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis. PMID:25278572

  7. Occult hepatitis B virus infection

    PubMed Central

    Kwak, Min-Sun; Kim, Yoon Jun

    2014-01-01

    Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of HBV DNA in the absence of detectable hepatitis B surface antigen. Since OBI was first described in the late 1970s, there has been increasing interest in this topic. The prevalence of OBI varies according to the different endemicity of HBV infection, cohort characteristics, and sensitivity and specificity of the methods used for detection. Although the exact mechanism of OBI has not been proved, intra-hepatic persistence of viral covalently closed circular DNA under the host’s strong immune suppression of HBV replication and gene expression seems to be a cause. OBI has important clinical significance in several conditions. First, OBI can be transmitted through transfusion, organ transplantation including orthotopic liver transplantation, or hemodialysis. Donor screening before blood transfusion, prophylaxis for high-risk organ transplantation recipients, and dialysis-specific infection-control programs should be considered to reduce the risk of transmission. Second, OBI may reactivate and cause acute hepatitis in immunocompromised patients or those receiving chemotherapy. Close HBV DNA monitoring and timely antiviral treatment can prevent HBV reactivation and consequent clinical deterioration. Third, OBI may contribute to the progression of hepatic fibrosis in patients with chronic liver disease including hepatitis C. Finally, OBI seems to be a risk factor for hepatocellular carcinoma by its direct proto-oncogenic effect and by indirectly causing persistent hepatic inflammation and fibrosis. However, this needs further investigation. We review published reports in the literature to gain an overview of the status of OBI and emphasize the clinical importance of OBI. PMID:25544873

  8. The dynamics of hepatitis B virus infection.

    PubMed Central

    Payne, R J; Nowak, M A; Blumberg, B S

    1996-01-01

    We consider a cellular model of infection by the hepatitis B virus and describe how it may be used to account for two important features of the disease, namely (i) the wide variety of manifestations of infection and the age dependence thereof, and (ii) the typically long delay before the development of virus-induced liver cancer (primary hepatocellular carcinoma). The model is based on the assumption that the liver is comprised of both immature and mature hepatocytes, with these two subpopulations of cells responding contrastingly upon infection by the virus. PMID:8692852

  9. The New World arenavirus Tacaribe virus induces caspase-dependent apoptosis in infected cells.

    PubMed

    Wolff, Svenja; Groseth, Allison; Meyer, Bjoern; Jackson, David; Strecker, Thomas; Kaufmann, Andreas; Becker, Stephan

    2016-04-01

    The Arenaviridae is a diverse and growing family of viruses that already includes more than 25 distinct species. While some of these viruses have a significant impact on public health, others appear to be non-pathogenic. At present little is known about the host cell responses to infection with different arenaviruses, particularly those found in the New World; however, apoptosis is known to play an important role in controlling infection of many viruses. Here we show that infection with Tacaribe virus (TCRV), which is widely considered the prototype for non-pathogenic arenaviruses, leads to stronger induction of apoptosis than does infection with its human-pathogenic relative Junín virus. TCRV-induced apoptosis occurred in several cell types during late stages of infection and was shown to be caspase-dependent, involving the activation of caspases 3, 7, 8 and 9. Further, UV-inactivated TCRV did not induce apoptosis, indicating that the activation of this process is dependent on active viral replication/transcription. Interestingly, when apoptosis was inhibited, growth of TCRV was not enhanced, indicating that apoptosis does not have a direct negative effect on TCRV infection in vitro. Taken together, our data identify and characterize an important virus-host cell interaction of the prototypic, non-pathogenic arenavirus TCRV, which provides important insight into the growing field of arenavirus research aimed at better understanding the diversity in responses to different arenavirus infections and their functional consequences.

  10. The New World arenavirus Tacaribe virus induces caspase-dependent apoptosis in infected cells.

    PubMed

    Wolff, Svenja; Groseth, Allison; Meyer, Bjoern; Jackson, David; Strecker, Thomas; Kaufmann, Andreas; Becker, Stephan

    2016-04-01

    The Arenaviridae is a diverse and growing family of viruses that already includes more than 25 distinct species. While some of these viruses have a significant impact on public health, others appear to be non-pathogenic. At present little is known about the host cell responses to infection with different arenaviruses, particularly those found in the New World; however, apoptosis is known to play an important role in controlling infection of many viruses. Here we show that infection with Tacaribe virus (TCRV), which is widely considered the prototype for non-pathogenic arenaviruses, leads to stronger induction of apoptosis than does infection with its human-pathogenic relative Junín virus. TCRV-induced apoptosis occurred in several cell types during late stages of infection and was shown to be caspase-dependent, involving the activation of caspases 3, 7, 8 and 9. Further, UV-inactivated TCRV did not induce apoptosis, indicating that the activation of this process is dependent on active viral replication/transcription. Interestingly, when apoptosis was inhibited, growth of TCRV was not enhanced, indicating that apoptosis does not have a direct negative effect on TCRV infection in vitro. Taken together, our data identify and characterize an important virus-host cell interaction of the prototypic, non-pathogenic arenavirus TCRV, which provides important insight into the growing field of arenavirus research aimed at better understanding the diversity in responses to different arenavirus infections and their functional consequences. PMID:26769540

  11. Considerations in the Use of Nonhuman Primate Models of Ebola Virus and Marburg Virus Infection.

    PubMed

    Geisbert, Thomas W; Strong, James E; Feldmann, Heinz

    2015-10-01

    The filoviruses, Ebola virus and Marburg virus, are zoonotic pathogens that cause severe hemorrhagic fever in humans and nonhuman primates (NHPs), with case-fatality rates ranging from 23% to 90%. The current outbreak of Ebola virus infection in West Africa, with >26 000 cases, demonstrates the long-underestimated public health danger that filoviruses pose as natural human pathogens. Currently, there are no vaccines or treatments licensed for human use. Licensure of any medical countermeasure may require demonstration of efficacy in the gold standard cynomolgus or rhesus macaque models of filovirus infection. Substantial progress has been made over the last decade in characterizing the filovirus NHP models. However, there is considerable debate over a variety of experimental conditions, including differences among filovirus isolates used, routes and doses of exposure, and euthanasia criteria, all of which may contribute to variability of results among different laboratories. As an example of the importance of understanding these differences, recent data with Ebola virus shows that an addition of a single uridine residue in the glycoprotein gene at the editing site attenuates the virus. Here, we draw on decades of experience working with filovirus-infected NHPs to provide a perspective on the importance of various experimental conditions.

  12. Considerations in the Use of Nonhuman Primate Models of Ebola Virus and Marburg Virus Infection

    PubMed Central

    Geisbert, Thomas W.; Strong, James E.; Feldmann, Heinz

    2015-01-01

    The filoviruses, Ebola virus and Marburg virus, are zoonotic pathogens that cause severe hemorrhagic fever in humans and nonhuman primates (NHPs), with case-fatality rates ranging from 23% to 90%. The current outbreak of Ebola virus infection in West Africa, with >26 000 cases, demonstrates the long-underestimated public health danger that filoviruses pose as natural human pathogens. Currently, there are no vaccines or treatments licensed for human use. Licensure of any medical countermeasure may require demonstration of efficacy in the gold standard cynomolgus or rhesus macaque models of filovirus infection. Substantial progress has been made over the last decade in characterizing the filovirus NHP models. However, there is considerable debate over a variety of experimental conditions, including differences among filovirus isolates used, routes and doses of exposure, and euthanasia criteria, all of which may contribute to variability of results among different laboratories. As an example of the importance of understanding these differences, recent data with Ebola virus shows that an addition of a single uridine residue in the glycoprotein gene at the editing site attenuates the virus. Here, we draw on decades of experience working with filovirus-infected NHPs to provide a perspective on the importance of various experimental conditions. PMID:26063223

  13. Why is co-infection with influenza virus and bacteria so difficult to control?

    PubMed Central

    Cauley, Linda S.; Vella, Anthony T.

    2015-01-01

    Influenza viruses are genetically labile pathogens which avoid immune detection by constantly changing their coat proteins. Most human infections are caused by mildly pathogenic viruses which rarely cause life-threatening disease in healthy people, but some individuals with a weakened immune system can experience severe complications. Widespread infections with highly pathogenic strains of influenza virus are less common, but have the potential to cause enormous death tolls among healthy adults if infection rates reach pandemic proportions. Increased virulence has been attributed to a variety of factors, including enhanced susceptibility to co-infection with common strains of bacteria. The mechanisms that facilitate dual infection are a major focus of current research, as preventative measures are needed to avert future pandemics PMID:25636959

  14. The Challenge of Respiratory Virus Infections in Hematopoietic Cell Transplant Recipients

    PubMed Central

    Boeckh, Michael

    2009-01-01

    Respiratory virus infections in hematopoietic cell transplant (HCT) recipients are a major cause of morbidity and mortality. While respiratory syncytial virus (RSV), human metapneumonvirus, parainfluenzaviruses, and influenza viruses are well known for their potential to cause fatal pneumonia, information is emerging only recently on the significance of the newly discovered viruses such as human coronaviruses NL63 and HKU1, and human bocavirus. Lymphopenia seems to be the most recent risk factors for progression to lower respiratory tract disease. Airflow obstruction is another complication of respiratory virus infections after HCT, and data to date indicate this complication may occur following parainfluenza virus and RSV infection. Infection control procedures are key for prevention. Unfortunately, there are no randomized treatment studies, which make the interpretation of the literature on interventions difficult. This article reviews the spectrum of pathogens, epidemiology, risk factors and clinical manifestations of infection, as well as recent advances in diagnostic and clinical management. PMID:18785968

  15. Emergence of a Highly Pathogenic Avian Influenza Virus from a Low-Pathogenic Progenitor

    PubMed Central

    Fusaro, Alice; Nelson, Martha I.; Bonfanti, Lebana; Mulatti, Paolo; Hughes, Joseph; Murcia, Pablo R.; Schivo, Alessia; Valastro, Viviana; Moreno, Ana; Holmes, Edward C.; Cattoli, Giovanni

    2014-01-01

    ABSTRACT Avian influenza (AI) viruses of the H7 subtype have the potential to evolve into highly pathogenic (HP) viruses that represent a major economic problem for the poultry industry and a threat to global health. However, the emergence of HPAI viruses from low-pathogenic (LPAI) progenitor viruses currently is poorly understood. To investigate the origin and evolution of one of the most important avian influenza epidemics described in Europe, we investigated the evolutionary and spatial dynamics of the entire genome of 109 H7N1 (46 LPAI and 63 HPAI) viruses collected during Italian H7N1 outbreaks between March 1999 and February 2001. Phylogenetic analysis revealed that the LPAI and HPAI epidemics shared a single ancestor, that the HPAI strains evolved from the LPAI viruses in the absence of reassortment, and that there was a parallel emergence of mutations among HPAI and later LPAI lineages. Notably, an ultradeep-sequencing analysis demonstrated that some of the amino acid changes characterizing the HPAI virus cluster were already present with low frequency within several individual viral populations from the beginning of the LPAI H7N1 epidemic. A Bayesian phylogeographic analysis revealed stronger spatial structure during the LPAI outbreak, reflecting the more rapid spread of the virus following the emergence of HPAI. The data generated in this study provide the most complete evolutionary and phylogeographic analysis of epidemiologically intertwined high- and low-pathogenicity viruses undertaken to date and highlight the importance of implementing prompt eradication measures against LPAI to prevent the appearance of viruses with fitness advantages and unpredictable pathogenic properties. IMPORTANCE The Italian H7 AI epidemic of 1999 to 2001 was one of the most important AI outbreaks described in Europe. H7 viruses have the ability to evolve into HP forms from LP precursors, although the mechanisms underlying this evolutionary transition are only poorly

  16. Interferon-γ Inhibits Ebola Virus Infection

    PubMed Central

    Rhein, Bethany A.; Powers, Linda S.; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K.; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A.

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks. PMID:26562011

  17. Heterotrimeric G-proteins facilitate resistance to plant pathogenic viruses in Arabidopsis thaliana (L.) Heynh.

    PubMed

    Brenya, Eric; Trusov, Yuri; Dietzgen, Ralf Georg; Botella, José Ramón

    2016-08-01

    Heterotrimeric G-proteins, consisting of Gα, Gβ and Gγ subunits, are important signal transducers in eukaryotes. In plants, G-protein-mediated signaling contributes to defense against a range of fungal and bacterial pathogens. Here we studied response of G-protein-deficient mutants to ssRNA viruses representing 2 different families: Cucumber mosaic virus (CMV) (Bromoviridae) and Turnip mosaic virus (TuMV) (Potyviridae). We found that development of spreading necrosis on infected plants was suppressed in the Gβ-deficient mutant (agb1-2) compared to wild type and Gα-deficient mutant (gpa1-4). In accordance, ion leakage caused by viral infection was also significantly reduced in agb1-2 compared to wild type and gpa1-4. Nevertheless, both viruses replicated better in agb1-2 plants, while gpa1-4 was similar to wild type. Analysis of pathogenesis-related genes showed that Gβ negatively regulated salicylic acid, jasmonic acid and abscisic acid marker genes during CMV and TuMV infections. Interestingly, analysis of salicylic acid deficient transgenic plants indicated that salicylic acid did not affect resistance against these viruses and did not influence the Gβ-mediated defense response. We conclude that heterotrimeric G-proteins play a positive role in defense against viral pathogens probably by promoting cell death. PMID:27454415

  18. Identification and characterization of a type III Trichomonas vaginalis virus in the protozoan pathogen Trichomonas vaginalis.

    PubMed

    Bessarab, Irina N; Nakajima, Rui; Liu, Hsing-Wei; Tai, Jung-Hsiang

    2011-02-01

    A type III Trichomonas vaginalis virus, which may be involved in transcriptional regulation of the major surface protein gene P270 of the protozoan pathogen Trichomonas vaginalis, was purified and characterized in the present study. The complete 4844-base-pair complementary DNA sequence of the viral genome reveals overlapping cap and pol genes with a putative ribosomal frame-shifting signal within the overlap region. The type III virus is related more closely to the type II virus than to the type I virus in the sequence of its ribosomal frameshift signal and in its capsid protein. Phylogenetic analysis revealed that these viruses could be grouped in the same clade as a genus distantly related to other genera in the family Totiviridae. Virus-induced P270 gene expression was only evident in Trichomonas vaginalis cells infected with either a type II or type III virus, but not with a type I virus. These findings suggest that transcription of the P270 gene is likely regulated by viral factors common to type II and type III viruses and thus provides important information for future investigation of virus-host interactions.

  19. Identification and characterization of a type III Trichomonas vaginalis virus in the protozoan pathogen Trichomonas vaginalis.

    PubMed

    Bessarab, Irina N; Nakajima, Rui; Liu, Hsing-Wei; Tai, Jung-Hsiang

    2011-02-01

    A type III Trichomonas vaginalis virus, which may be involved in transcriptional regulation of the major surface protein gene P270 of the protozoan pathogen Trichomonas vaginalis, was purified and characterized in the present study. The complete 4844-base-pair complementary DNA sequence of the viral genome reveals overlapping cap and pol genes with a putative ribosomal frame-shifting signal within the overlap region. The type III virus is related more closely to the type II virus than to the type I virus in the sequence of its ribosomal frameshift signal and in its capsid protein. Phylogenetic analysis revealed that these viruses could be grouped in the same clade as a genus distantly related to other genera in the family Totiviridae. Virus-induced P270 gene expression was only evident in Trichomonas vaginalis cells infected with either a type II or type III virus, but not with a type I virus. These findings suggest that transcription of the P270 gene is likely regulated by viral factors common to type II and type III viruses and thus provides important information for future investigation of virus-host interactions. PMID:21110050

  20. Regulatory T cells enhance persistence of the zoonotic pathogen Seoul virus in its reservoir host.

    PubMed

    Easterbrook, Judith D; Zink, M Christine; Klein, Sabra L

    2007-09-25

    Hantaviruses are zoonotic pathogens that maintain a persistent infection in their reservoir hosts, yet the mechanisms mediating persistence remain unknown. Regulatory T cell responses cause persistent infection by suppressing proinflammatory and effector T cell activity; hantaviruses may exploit these responses to cause persistence. To test this hypothesis, male Norway rats were inoculated with Seoul virus and regulatory T cells were monitored during infection. Increased numbers of CD4(+)CD25(+)Forkhead box P3(+) T cells and expression of Forkhead box P3 and TGF-beta were observed in the lungs of male rats during persistent Seoul virus infection. To determine whether regulatory T cells modulate Seoul virus persistence, regulatory T cells were inactivated in male rats by using an anti-rat CD25 monoclonal antibody (NDS-63). Inactivation of regulatory T cells reduced the amount of Seoul virus RNA present in the lungs and the proportion of animals shedding viral RNA in saliva. Because regulatory T cells suppress proinflammatory-induced pathogenesis, pathologic observations in the lungs were evaluated during infection. Subclinical acute multifocal areas of hemorrhage and edema were noted in the lungs during infection; inactivation of regulatory T cells reduced the amount of pathologic foci. Expression of TNF was suppressed during the persistent phase of infection; inactivation of regulatory T cells eliminated the suppression of TNF. Taken together, these data suggest that regulatory T cells mediate Seoul virus persistence, possibly through elevated transcription and synthesis of TGF-beta and suppression of TNF. These data provide evidence of regulatory T cell involvement in the persistence of a zoonotic pathogen in its natural reservoir host.

  1. Background review for diagnostic test development for Zika virus infection

    PubMed Central

    Charrel, Rémi N; Leparc-Goffart, Isabelle; Pas, Suzan; de Lamballerie, Xavier; Koopmans, Marion; Reusken, Chantal

    2016-01-01

    Abstract Objective To review the state of knowledge about diagnostic testing for Zika virus infection and identify areas of research needed to address the current gaps in knowledge. Methods We made a non-systematic review of the published literature about Zika virus and supplemented this with information from commercial diagnostic test kits and personal communications with researchers in European preparedness networks. The review covered current knowledge about the geographical spread, pathogen characteristics, life cycle and infection kinetics of the virus. The available molecular and serological tests and biosafety issues are described and discussed in the context of the current outbreak strain. Findings We identified the following areas of research to address current knowledge gaps: (i) an urgent assessment of the laboratory capacity and capability of countries to detect Zika virus; (ii) rapid and extensive field validation of the available molecular and serological tests in areas with and without Zika virus transmission, with a focus on pregnant women; (iii) monitoring the genomic diversity of circulating Zika virus strains; (iv) prospective studies into the virus infection kinetics, focusing on diagnostic sampling (specimen types, combinations and timings); and (v) developing external quality assessments for molecular and serological testing, including differential diagnosis for similar viruses and symptom clusters. The availability of reagents for diagnostic development (virus strains and antigens, quantified viral ribonucleic acid) needs to be facilitated. Conclusion An international laboratory response is needed, including preparation of protocols for prospective studies to address the most pressing information needs. PMID:27516635

  2. Permissive and restricted virus infection of murine embryonic stem cells

    PubMed Central

    Wash, Rachael; Calabressi, Sabrina; Franz, Stephanie; Griffiths, Samantha J.; Goulding, David; Tan, E-Pien; Wise, Helen; Digard, Paul; Haas, Jürgen; Efstathiou, Stacey

    2012-01-01

    Recent RNA interference (RNAi) studies have identified many host proteins that modulate virus infection, but small interfering RNA ‘off-target’ effects and the use of transformed cell lines limit their conclusiveness. As murine embryonic stem (mES) cells can be genetically modified and resources exist where many and eventually all known mouse genes are insertionally inactivated, it was reasoned that mES cells would provide a useful alternative to RNAi screens. Beyond allowing investigation of host–pathogen interactions in vitro, mES cells have the potential to differentiate into other primary cell types, as well as being used to generate knockout mice for in vivo studies. However, mES cells are poorly characterized for virus infection. To investigate whether ES cells can be used to explore host–virus interactions, this study characterized the responses of mES cells following infection by herpes simplex virus type 1 (HSV-1) and influenza A virus. HSV-1 replicated lytically in mES cells, although mES cells were less permissive than most other cell types tested. Influenza virus was able to enter mES cells and express some viral proteins, but the replication cycle was incomplete and no infectious virus was produced. Knockdown of the host protein AHCYL1 in mES cells reduced HSV-1 replication, showing the potential for using mES cells to study host–virus interactions. Transcriptional profiling, however, indicated the lack of an efficient innate immune response in these cells. mES cells may thus be useful to identify host proteins that play a role in virus replication, but they are not suitable to determine factors that are involved in innate host defence. PMID:22815272

  3. Herpes simplex virus infections in neonates and early childhood.

    PubMed

    Kimberlin, David W

    2005-10-01

    Of the commonly considered congenital infections, those caused by cytomegalovirus (CMV), syphilis, and herpes simplex virus (HSV) are frequently (CMV, HSV) or exclusively (syphilis) acquired sexually by the mother, with subsequent transmission to the developing fetus. Of the other commonly considered congenital infections, including rubella and toxoplasma infections, the mother is exposed to the infectious agent via interpersonal or environmental contacts. Unlike each of these other pathogens, which are transmitted transplacentally to the developing fetus following maternal infection though, HSV usually is transmitted perinatally as the neonate is exposed to the virus during passage through an infected birth canal. This difference in timing of acquisition of infection has had important consequence in the therapeutic advances achieved during the last 30 years in the management of neonatal HSV infections. Because the time period between the acquisition of infection and initiation of effective antiviral therapy is shorter in neonatal herpes than in congenital toxoplasmosis or CMV infections, the outcomes of therapy have the potential to be markedly different. This article will summarize the current state of neonatal HSV disease presentation, diagnosis, and management. PMID:16210107

  4. Visual inspections of nursery stock fail to protect new plantings from Blueberry scorch virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Blueberry scorch virus (BlScV) is one of the most pervasive pathogens of highbush blueberry. The virus is aphid-vectored and exhibits a latent period between infection and symptom expression of up to 4 years. In many cases, we have observed BlScV symptom expression in new fields that is inconsistent...

  5. The Genus Aeromonas: Taxonomy, Pathogenicity, and Infection

    PubMed Central

    Janda, J. Michael; Abbott, Sharon L.

    2010-01-01

    Summary: Over the past decade, the genus Aeromonas has undergone a number of significant changes of practical importance to clinical microbiologists and scientists alike. In parallel with the molecular revolution in microbiology, several new species have been identified on a phylogenetic basis, and the genome of the type species, A. hydrophila ATCC 7966, has been sequenced. In addition to established disease associations, Aeromonas has been shown to be a significant cause of infections associated with natural disasters (hurricanes, tsunamis, and earthquakes) and has been linked to emerging or new illnesses, including near-drowning events, prostatitis, and hemolytic-uremic syndrome. Despite these achievements, issues still remain regarding the role that Aeromonas plays in bacterial gastroenteritis, the extent to which species identification should be attempted in the clinical laboratory, and laboratory reporting of test results from contaminated body sites containing aeromonads. This article provides an extensive review of these topics, in addition to others, such as taxonomic issues, microbial pathogenicity, and antimicrobial resistance markers. PMID:20065325

  6. [Imported Zika virus infection in the Netherlands].

    PubMed

    von Eije, Karin J; Schinkel, Janke; van den Kerkhof, J H C T Hans; Schreuder, Imke; de Jong, Menno D; Grobusch, Martin P; Goorhuis, Abraham

    2015-01-01

    Since mid-2015, a rapidly expanding outbreak of Zika virus infection is spreading across Latin America and the Caribbean. Although Zika virus infection usually causes only mild disease, the World Health Organization has declared the epidemiological association with the occurrence of congenital microcephaly and neurological complications a 'Public Health Emergency of International Concern' and urged the international community to mount a coordinated international response aimed to protect people at risk, especially pregnant women. In December 2015, the first case of imported Zika virus infection in the Netherlands was diagnosed in a returned traveler from Surinam. To date, more than 20 cases have been reported in The Netherlands, all imported from Surinam. We describe the epidemiology, clinical aspects, diagnostic challenges and the existing evidence to date that link Zika virus infection to complications.

  7. Human immunodeficiency virus infection and pneumothorax

    PubMed Central

    Terzi, Eirini; Zarogoulidis, Konstantinos; Kougioumtzi, Ioanna; Dryllis, Georgios; Kioumis, Ioannis; Pitsiou, Georgia; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Tsiouda, Theodora; Madesis, Athanasios; Karaiskos, Theodoros

    2014-01-01

    Pneumothorax is a serious and relatively frequent complication of human immunodeficiency virus (HIV) infection that may associate with increased morbidity and mortality and may prove difficult to manage, especially in patients with acquired immunodeficiency syndrome (AIDS). PMID:25337392

  8. Characterization of duck H5N1 influenza viruses with differing pathogenicity in mallard (Anas platyrhynchos) ducks.

    PubMed

    Tang, Yinghua; Wu, Peipei; Peng, Daxin; Wang, Xiaobo; Wan, Hongquan; Zhang, Pinghu; Long, Jinxue; Zhang, Wenjun; Li, Yanfang; Wang, Wenbin; Zhang, Xiaorong; Liu, Xiufan

    2009-12-01

    A number of H5N1 influenza outbreaks have occurred in aquatic birds in Asia. As aquatic birds are the natural reservoir of influenza A viruses and do not usually show clinical disease upon infection, the repeated H5N1 outbreaks have highlighted the importance of continuous surveillance on H5N1 viruses in aquatic birds. In the present study we characterized the biological properties of four H5N1 avian influenza viruses, which had been isolated from ducks, in different animal models. In specific pathogen free (SPF) chickens, all four isolates were highly pathogenic. In SPF mice, the S and Y isolates were moderately pathogenic. However, in mallard ducks, two isolates had low pathogenicity, while the other two were highly pathogenic and caused lethal infection. A representative isolate with high pathogenicity in ducks caused systemic infection and replicated effectively in all 10 organs tested in challenged ducks, whereas a representative isolate with low pathogenicity in ducks was only detected in some organs in a few challenged ducks. Comparison of complete genomic sequences from the four isolates showed that the same amino acid residues that have been reported to be associated with virulence and host adaption/restriction of influenza viruses were present in the PB2, HA, NA, M and NS genes, while the amino acid residues at the HA cleavage site were diverse. From these results it appeared that the virulence of H5N1 avian influenza viruses was increased for ducks and that amino acid substitutions at the HA cleavage site might have contributed to the differing pathogenicity of these isolates in mallards. A procedure for the intravenous pathogenicity index test in a mallard model for assessing the virulence of H5/H7 subtype avian influenza viruses in waterfowl is described.

  9. Methods used to study respiratory virus infection.

    PubMed

    Flaño, Emilio; Jewell, Nancy A; Durbin, Russell K; Durbin, Joan E

    2009-06-01

    This unit describes protocols for infecting the mouse respiratory tract, and assaying virus replication and host response in the lung. Respiratory infections are the leading cause of acute illness worldwide, affecting mostly infants and children in developing countries. The purpose of this unit is to provide a basic strategy and protocols to study the pathogenesis and immunology of respiratory virus infection using the mouse as an animal model. The procedures include: (1) basic techniques for mouse infection, tissue sampling, and preservation, (2) determination of viral titers, isolation and analysis of lymphocytes and dendritic cells using flow-cytometry, and (3) lung histology, immunohistochemistry, and in situ hybridization.

  10. METHODS USED TO STUDY RESPIRATORY VIRUS INFECTION

    PubMed Central

    Flaño, Emilio; Jewell, Nancy A.; Durbin, Russell K.; Durbin, Joan E.

    2009-01-01

    This unit describes protocols for infecting the mouse respiratory tract, and assaying virus replication and host response in the lung. Respiratory infections are the leading cause of acute illness worldwide, affecting mostly infants and children in developing countries. The purpose of this unit is to provide the readers with a basic strategy and protocols to study the pathogenesis and immunology of respiratory virus infection using the mouse as an animal model. The procedures include: (i) basic techniques for mouse infection, tissue sampling and preservation, (ii) determination of viral titers, isolation and analysis of lymphocytes and dendritic cells using flow-cytometry, and (iii) lung histology, immunohistochemistry and in situ hybridization. PMID:19499505

  11. Chikungunya Virus Infection of Aedes Mosquitoes.

    PubMed

    Wong, Hui Vern; Chan, Yoke Fun; Sam, I-Ching; Sulaiman, Wan Yusof Wan; Vythilingam, Indra

    2016-01-01

    In vivo infection of mosquitoes is an important method to study and characterize arthropod-borne viruses. Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is transmitted primarily by Aedes mosquitoes. In this chapter, we describe a protocol for infection of CHIKV in two species of Aedes mosquitoes, Aedes aegypti and Aedes albopictus, together with the isolation of CHIKV in different parts of the infected mosquito such as midgut, legs, wings, salivary gland, head, and saliva. This allows the study of viral infection, replication and dissemination within the mosquito vector. PMID:27233266

  12. Herpes simplex virus infection during pregnancy.

    PubMed

    Stephenson-Famy, Alyssa; Gardella, Carolyn

    2014-12-01

    Genital herpes in pregnancy continues to cause significant maternal morbidity, with an increasing number of infections being due to oral-labial transmission of herpes simplex virus (HSV)-1. Near delivery, primary infections with HSV-1 or HSV-2 carry the highest risk of neonatal herpes infection, which is a rare but potentially devastating disease for otherwise healthy newborns. Prevention efforts have been limited by lack of an effective intervention for preventing primary infections and the unclear role of routine serologic testing.

  13. Role of natural killer cells in innate protection against lethal ebola virus infection.

    PubMed

    Warfield, Kelly L; Perkins, Jeremy G; Swenson, Dana L; Deal, Emily M; Bosio, Catharine M; Aman, M Javad; Yokoyama, Wayne M; Young, Howard A; Bavari, Sina

    2004-07-19

    Ebola virus is a highly lethal human pathogen and is rapidly driving many wild primate populations toward extinction. Several lines of evidence suggest that innate, nonspecific host factors are potentially critical for survival after Ebola virus infection. Here, we show that nonreplicating Ebola virus-like particles (VLPs), containing the glycoprotein (GP) and matrix protein virus protein (VP)40, administered 1-3 d before Ebola virus infection rapidly induced protective immunity. VLP injection enhanced the numbers of natural killer (NK) cells in lymphoid tissues. In contrast to live Ebola virus, VLP treatment of NK cells enhanced cytokine secretion and cytolytic activity against NK-sensitive targets. Unlike wild-type mice, treatment of NK-deficient or -depleted mice with VLPs had no protective effect against Ebola virus infection and NK cells treated with VLPs protected against Ebola virus infection when adoptively transferred to naive mice. The mechanism of NK cell-mediated protection clearly depended on perforin, but not interferon-gamma secretion. Particles containing only VP40 were sufficient to induce NK cell responses and provide protection from infection in the absence of the viral GP. These findings revealed a decisive role for NK cells during lethal Ebola virus infection. This work should open new doors for better understanding of Ebola virus pathogenesis and direct the development of immunotherapeutics, which target the innate immune system, for treatment of Ebola virus infection.

  14. Systemic Spread and Propagation of a Plant-Pathogenic Virus in European Honeybees, Apis mellifera

    PubMed Central

    Li, Ji Lian; Cornman, R. Scott; Evans, Jay D.; Pettis, Jeffery S.; Zhao, Yan; Murphy, Charles; Peng, Wen Jun; Wu, Jie; Hamilton, Michele; Boncristiani, Humberto F.; Zhou, Liang; Hammond, John; Chen, Yan Ping

    2014-01-01

    ABSTRACT Emerging and reemerging diseases that result from pathogen host shifts are a threat to the health of humans and their domesticates. RNA viruses have extremely high mutation rates and thus represent a significant source of these infectious diseases. In the present study, we showed that a plant-pathogenic RNA virus, tobacco ringspot virus (TRSV), could replicate and produce virions in honeybees, Apis mellifera, resulting in infections that were found throughout the entire body. Additionally, we showed that TRSV-infected individuals were continually present in some monitored colonies. While intracellular life cycle, species-level genetic variation, and pathogenesis of the virus in honeybee hosts remain to be determined, the increasing prevalence of TRSV in conjunction with other bee viruses from spring toward winter in infected colonies was associated with gradual decline of host populations and winter colony collapse, suggesting the negative impact of the virus on colony survival. Furthermore, we showed that TRSV was also found in ectoparasitic Varroa mites that feed on bee hemolymph, but in those instances the virus was restricted to the gastric cecum of Varroa mites, suggesting that Varroa mites may facilitate the spread of TRSV in bees but do not experience systemic invasion. Finally, our phylogenetic analysis revealed that TRSV isolates from bees, bee pollen, and Varroa mites clustered together, forming a monophyletic clade. The tree topology indicated that the TRSVs from arthropod hosts shared a common ancestor with those from plant hosts and subsequently evolved as a distinct lineage after transkingdom host alteration. This study represents a unique example of viruses with host ranges spanning both the plant and animal kingdoms. PMID:24449751

  15. Life-Threatening Sochi Virus Infections, Russia

    PubMed Central

    Tkachenko, Evgeniy A.; Morozov, Vyacheslav G.; Yunicheva, Yulia V.; Pilikova, Olga M.; Malkin, Gennadiy; Ishmukhametov, Aydar A.; Heinemann, Patrick; Witkowski, Peter T.; Klempa, Boris; Dzagurova, Tamara K.

    2015-01-01

    Sochi virus was recently identified as a new hantavirus genotype carried by the Black Sea field mouse, Apodemus ponticus. We evaluated 62 patients in Russia with Sochi virus infection. Most clinical cases were severe, and the case-fatality rate was as high as 14.5%. PMID:26584463

  16. Life-Threatening Sochi Virus Infections, Russia.

    PubMed

    Kruger, Detlev H; Tkachenko, Evgeniy A; Morozov, Vyacheslav G; Yunicheva, Yulia V; Pilikova, Olga M; Malkin, Gennadiy; Ishmukhametov, Aydar A; Heinemann, Patrick; Witkowski, Peter T; Klempa, Boris; Dzagurova, Tamara K

    2015-12-01

    Sochi virus was recently identified as a new hantavirus genotype carried by the Black Sea field mouse, Apodemus ponticus. We evaluated 62 patients in Russia with Sochi virus infection. Most clinical cases were severe, and the case-fatality rate was as high as 14.5%.

  17. Detection of Zika Virus Infection in Thailand, 2012–2014

    PubMed Central

    Buathong, Rome; Hermann, Laura; Thaisomboonsuk, Butsaya; Rutvisuttinunt, Wiriya; Klungthong, Chonticha; Chinnawirotpisan, Piyawan; Manasatienkij, Wudtichai; Nisalak, Ananda; Fernandez, Stefan; Yoon, In-Kyu; Akrasewi, Passakorn; Plipat, Tanarak

    2015-01-01

    Zika virus (ZIKV) is an emerging mosquito-borne pathogen with reported cases in Africa, Asia, and large outbreaks in the Pacific. No autochthonous ZIKV infections have been confirmed in Thailand. However, there have been several cases reported in travelers returning from Thailand. Here we report seven cases of acute ZIKV infection in Thai residents across the country confirmed by molecular or serological testing including sequence data. These endemic cases, combined with previous reports in travelers, provide evidence that ZIKV is widespread throughout Thailand. PMID:26101272

  18. Detection of Zika Virus Infection in Thailand, 2012-2014.

    PubMed

    Buathong, Rome; Hermann, Laura; Thaisomboonsuk, Butsaya; Rutvisuttinunt, Wiriya; Klungthong, Chonticha; Chinnawirotpisan, Piyawan; Manasatienkij, Wudtichai; Nisalak, Ananda; Fernandez, Stefan; Yoon, In-Kyu; Akrasewi, Passakorn; Plipat, Tanarak

    2015-08-01

    Zika virus (ZIKV) is an emerging mosquito-borne pathogen with reported cases in Africa, Asia, and large outbreaks in the Pacific. No autochthonous ZIKV infections have been confirmed in Thailand. However, there have been several cases reported in travelers returning from Thailand. Here we report seven cases of acute ZIKV infection in Thai residents across the country confirmed by molecular or serological testing including sequence data. These endemic cases, combined with previous reports in travelers, provide evidence that ZIKV is widespread throughout Thailand.

  19. Pathogenic hantaviruses direct the adherence of quiescent platelets to infected endothelial cells.

    PubMed

    Gavrilovskaya, Irina N; Gorbunova, Elena E; Mackow, Erich R

    2010-05-01

    Hantavirus infections are noted for their ability to infect endothelial cells, cause acute thrombocytopenia, and trigger 2 vascular-permeability-based diseases. However, hantavirus infections are not lytic, and the mechanisms by which hantaviruses cause capillary permeability and thrombocytopenia are only partially understood. The role of beta(3) integrins in hemostasis and the inactivation of beta(3) integrin receptors by pathogenic hantaviruses suggest the involvement of hantaviruses in altered platelet and endothelial cell functions that regulate permeability. Here, we determined that pathogenic hantaviruses bind to quiescent platelets via a beta(3) integrin-dependent mechanism. This suggests that platelets may contribute to hantavirus dissemination within infected patients and provides a means by which hantavirus binding to beta(3) integrin receptors prevents platelet activation. The ability of hantaviruses to bind platelets further suggested that cell-associated hantaviruses might recruit platelets to the endothelial cell surface. Our findings indicate that Andes virus (ANDV)- or Hantaan virus (HTNV)-infected endothelial cells specifically direct the adherence of calcein-labeled platelets. In contrast, cells comparably infected with nonpathogenic Tula virus (TULV) failed to recruit platelets to the endothelial cell surface. Platelet adherence was dependent on endothelial cell beta(3) integrins and neutralized by the addition of the anti-beta(3) Fab fragment, c7E3, or specific ANDV- or HTNV-neutralizing antibodies. These findings indicate that pathogenic hantaviruses displayed on the surface of infected endothelial cells bind platelets and that a platelet layer covers the surface of infected endothelial cells. This fundamentally changes the appearance of endothelial cells and has the potential to alter cellular immune responses, platelet activation, and endothelial cell functions that affect vascular permeability. Hantavirus-directed platelet quiescence and

  20. Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response.

    PubMed

    Reese, Tiffany A; Bi, Kevin; Kambal, Amal; Filali-Mouhim, Ali; Beura, Lalit K; Bürger, Matheus C; Pulendran, Bali; Sekaly, Rafick-Pierre; Jameson, Stephen C; Masopust, David; Haining, W Nicholas; Virgin, Herbert W

    2016-05-11

    Immune responses differ between laboratory mice and humans. Chronic infection with viruses and parasites are common in humans, but are absent in laboratory mice, and thus represent potential contributors to inter-species differences in immunity. To test this, we sequentially infected laboratory mice with herpesviruses, influenza, and an intestinal helminth and compared their blood immune signatures to mock-infected mice before and after vaccination against yellow fever virus (YFV-17D). Sequential infection altered pre- and post-vaccination gene expression, cytokines, and antibodies in blood. Sequential pathogen exposure induced gene signatures that recapitulated those seen in blood from pet store-raised versus laboratory mice, and adult versus cord blood in humans. Therefore, basal and vaccine-induced murine immune responses are altered by infection with agents common outside of barrier facilities. This raises the possibility that we can improve mouse models of vaccination and immunity by selective microbial exposure of laboratory animals to mimic that of humans. PMID:27107939

  1. New method for the assessment of molluscum contagiosum virus infectivity.

    PubMed

    Sherwani, Subuhi; Blythe, Niamh; Farleigh, Laura; Bugert, Joachim J

    2012-01-01

    Molluscum contagiosum virus (MCV), a poxvirus pathogenic for humans, replicates well in human skin in vivo, but not in vitro in standard monolayer cell cultures. In order to determine the nature of the replication deficiency in vitro, the MCV infection process in standard culture has to be studied step by step. The method described in this chapter uses luciferase and GFP reporter constructs to measure poxviral mRNA transcription activity in cells in standard culture infected with known quantities of MCV or vaccinia virus. Briefly, MCV isolated from human tissue specimen is quantitated by PCR and used to infect human HEK293 cells, selected for ease of transfection. The cells are subsequently transfected with a reporter plasmid encoding firefly luciferase gene under the control of a synthetic early/late poxviral promoter and a control plasmid encoding a renilla luciferase reporter under the control of a eukaryotic promoter. After 16 h, cells are harvested and tested for expression of luciferase. MCV genome units are quantitated by PCR targeting a genome area conserved between MCV and vaccinia virus. Using a GFP reporter plasmid, this method can be further used to infect a series of epithelial and fibroblast-type cell lines of human and animal origin to microscopically visualize MCV-infected cells, to assess late promoter activation, and, using these parameters, to optimize MCV infectivity and gene expression in more complex eukaryotic cell culture models. PMID:22688765

  2. In ovo and in vitro susceptibility of American alligators (Alligator mississippiensis) to avian influenza virus infection.

    PubMed

    Temple, Bradley L; Finger, John W; Jones, Cheryl A; Gabbard, Jon D; Jelesijevic, Tomislav; Uhl, Elizabeth W; Hogan, Robert J; Glenn, Travis C; Tompkins, S Mark

    2015-01-01

    Avian influenza has emerged as one of the most ubiquitous viruses within our biosphere. Wild aquatic birds are believed to be the primary reservoir of all influenza viruses; however, the spillover of H5N1 highly pathogenic avian influenza (HPAI) and the recent swine-origin pandemic H1N1 viruses have sparked increased interest in identifying and understanding which and how many species can be infected. Moreover, novel influenza virus sequences were recently isolated from New World bats. Crocodilians have a slow rate of molecular evolution and are the sister group to birds; thus they are a logical reptilian group to explore susceptibility to influenza virus infection and they provide a link between birds and mammals. A primary American alligator (Alligator mississippiensis) cell line, and embryos, were infected with four, low pathogenic avian influenza (LPAI) strains to assess susceptibility to infection. Embryonated alligator eggs supported virus replication, as evidenced by the influenza virus M gene and infectious virus detected in allantoic fluid and by virus antigen staining in embryo tissues. Primary alligator cells were also inoculated with the LPAI viruses and showed susceptibility based upon antigen staining; however, the requirement for trypsin to support replication in cell culture limited replication. To assess influenza virus replication in culture, primary alligator cells were inoculated with H1N1 human influenza or H5N1 HPAI viruses that replicate independent of trypsin. Both viruses replicated efficiently in culture, even at the 30 C temperature preferred by the alligator cells. This research demonstrates the ability of wild-type influenza viruses to infect and replicate within two crocodilian substrates and suggests the need for further research to assess crocodilians as a species potentially susceptible to influenza virus infection.

  3. Global Reprogramming of Host SUMOylation during Influenza Virus Infection

    PubMed Central

    Domingues, Patricia; Golebiowski, Filip; Tatham, Michael H.; Lopes, Antonio M.; Taggart, Aislynn; Hay, Ronald T.; Hale, Benjamin G.

    2015-01-01

    Summary Dynamic nuclear SUMO modifications play essential roles in orchestrating cellular responses to proteotoxic stress, DNA damage, and DNA virus infection. Here, we describe a non-canonical host SUMOylation response to the nuclear-replicating RNA pathogen, influenza virus, and identify viral RNA polymerase activity as a major contributor to SUMO proteome remodeling. Using quantitative proteomics to compare stress-induced SUMOylation responses, we reveal that influenza virus infection triggers unique re-targeting of SUMO to 63 host proteins involved in transcription, mRNA processing, RNA quality control, and DNA damage repair. This is paralleled by widespread host deSUMOylation. Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes. Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression. Our global characterization of influenza virus-triggered SUMO redistribution provides a proteomic resource to understand host nuclear SUMOylation responses to infection. PMID:26549460

  4. Spontaneous substitutions in the vicinity of the V3 analog affect cell tropism and pathogenicity of simian immunodeficiency virus.

    PubMed Central

    Hirsch, V M; Martin, J E; Dapolito, G; Elkins, W R; London, W T; Goldstein, S; Johnson, P R

    1994-01-01

    Simian immunodeficiency virus (SIV) exists within tissues of infected macaques as a mixture of diverse genotypes. The goal of this study was to investigate the biologic significance of this variation in terms of cellular tropism and pathogenicity. PCR was used to amplify and clone 3'-half genomes from the spleen of an immunodeficiency SIV-infected pig-tailed macaque (Macaca nemestrina). Eight infectious clones were generated by ligation of respective 3' clones into a related SIVsm 5' clone, and virus stocks were generated by transient transfection. Four of these viruses were infectious for macaque peripheral blood mononuclear cells (PBMC) or monocyte-derived macrophages (MDM). Three viruses with distinct tropism for macaque PBMC or MDM were tested for in vivo infectivity and pathogenicity. The ability of these three viruses to infect PBMC and macrophages correlated with differences in infectivity and pathogenicity. Thus, a virus that was infectious for both PBMC and MDM was highly infectious for macaques and induced AIDS in half of the inoculated animals. In contrast, virus that was less infectious for PBMC and not infectious for MDM induced only transient viremia. Finally, a virus that was not infectious for either primary cell type did not infect macaques. Chimeric clones exchanging portions of the envelope gene of the 62A and smH4 molecular clones and a series of point mutants were used to map the determinant of tropism to a 60-amino-acid region of gp120 encompassing the V3 analog of SIV. Naturally occurring mutations within this region were critical for determining tropism and, as a result, pathogenicity of these SIVsm clones. Images PMID:8139042

  5. Health care-associated hepatitis C virus infection

    PubMed Central

    Pozzetto, Bruno; Memmi, Meriam; Garraud, Olivier; Roblin, Xavier; Berthelot, Philippe

    2014-01-01

    Hepatitis C virus (HCV) is a blood-borne pathogen that has a worldwide distribution and infects millions of people. Care-associated HCV infections represented a huge part of hepatitis C burden in the past via contaminated blood and unsafe injections and continue to be a serious problem of public health. The present review proposes a panorama of health care-associated HCV infections via the three mode of contamination that have been identified: (1) infected patient to non-infected patient; (2) infected patient to non-infected health care worker (HCW); and (3) infected HCW to non infected patient. For each condition, the circumstances of contamination are described together with the means to prevent them. As a whole, the more important risk is represented by unsafe practices regarding injections, notably with the improper use of multidose vials used for multiple patients. The questions of occupational exposures and infected HCWs are also discussed. In terms of prevention and surveillance, the main arm for combating care-associated HCV infections is the implementation of standard precautions in all the fields of cares, with training programs and audits to verify their good application. HCWs must be sensitized to the risk of blood-borne pathogens, notably by the use of safety devices for injections and good hygiene practices in the operating theatre and in all the invasive procedures. The providers performing exposed-prone procedures must monitor their HCV serology regularly in order to detect early any primary infection and to treat it without delay. With the need to stay vigilant because HCV infection is often a hidden risk, it can be hoped that the number of people infected by HCV via health care will decrease very significantly in the next years. PMID:25516637

  6. Virus Infection-Induced Bronchial Asthma Exacerbation

    PubMed Central

    Yamaya, Mutsuo

    2012-01-01

    Infection with respiratory viruses, including rhinoviruses, influenza virus, and respiratory syncytial virus, exacerbates asthma, which is associated with processes such as airway inflammation, airway hyperresponsiveness, and mucus hypersecretion. In patients with viral infections and with infection-induced asthma exacerbation, inflammatory mediators and substances, including interleukins (ILs), leukotrienes and histamine, have been identified in the airway secretions, serum, plasma, and urine. Viral infections induce an accumulation of inflammatory cells in the airway mucosa and submucosa, including neutrophils, lymphocytes and eosinophils. Viral infections also enhance the production of inflammatory mediators and substances in airway epithelial cells, mast cells, and other inflammatory cells, such as IL-1, IL-6, IL-8, GM-CSF, RANTES, histamine, and intercellular adhesion molecule-1. Viral infections affect the barrier function of the airway epithelial cells and vascular endothelial cells. Recent reports have demonstrated augmented viral production mediated by an impaired interferon response in the airway epithelial cells of asthma patients. Several drugs used for the treatment of bronchial asthma reduce viral and pro-inflammatory cytokine release from airway epithelial cells infected with viruses. Here, I review the literature on the pathogenesis of the viral infection-induced exacerbation of asthma and on the modulation of viral infection-induced airway inflammation. PMID:22966430

  7. Molecular Biology of Hepatitis B Virus Infection

    PubMed Central

    Seeger, Christoph; Mason, William S.

    2015-01-01

    Human hepatitis B virus (HBV) is the prototype of a family of small DNA viruses that productively infect hepatocytes, the major cell of the liver, and replicate by reverse transcription of a terminally redundant viral RNA, the pregenome. Upon infection, the circular, partially double-stranded virion DNA is converted in the nucleus to a covalently closed circular DNA (cccDNA) that assembles into a minichromosome, the template for viral mRNA synthesis. Infection of hepatocytes is non-cytopathic. Infection of the liver may be either transient (<6 months) or chronic and life long, depending on the ability of the host immune response to clear the infection. Chronic infections can cause immune mediated liver damage progressing to cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of carcinogenesis are unclear. Antiviral therapies with nucleoside analog inhibitors of viral DNA synthesis delay sequelae, but cannot cure HBV infections due to the persistence of cccDNA in hepatocytes. PMID:25759099

  8. Deletion of the meq gene significantly decreases immunosuppression in chickens caused by pathogenic marek's disease virus

    PubMed Central

    2011-01-01

    Background Marek's disease virus (MDV) causes an acute lymphoproliferative disease in chickens, resulting in immunosuppression, which is considered to be an integral aspect of the pathogenesis of Marek's disease (MD). A recent study showed that deletion of the Meq gene resulted in loss of transformation of T-cells in chickens and a Meq-null virus, rMd5ΔMeq, could provide protection superior to CVI988/Rispens. Results In the present study, to investigate whether the Meq-null virus could be a safe vaccine candidate, we constructed a Meq deletion strain, GX0101ΔMeq, by deleting both copies of the Meq gene from a pathogenic MDV, GX0101 strain, which was isolated in China. Pathogenesis experiments showed that the GX0101ΔMeq virus was fully attenuated in specific pathogen-free chickens because none of the infected chickens developed Marek's disease-associated lymphomas. The study also evaluated the effects of GX0101ΔMeq on the immune system in chickens after infection with GX0101ΔMeq virus. Immune system variables, including relative lymphoid organ weight, blood lymphocytes and antibody production following vaccination against AIV and NDV were used to assess the immune status of chickens. Experimental infection with GX0101ΔMeq showed that deletion of the Meq gene significantly decreased immunosuppression in chickens caused by pathogenic MDV. Conclusion These findings suggested that the Meq gene played an important role not only in tumor formation but also in inducing immunosuppressive effects in MDV-infected chickens. PMID:21205328

  9. Inactivation of pathogenic viruses by plant-derived tannins: strong effects of extracts from persimmon (Diospyros kaki) on a broad range of viruses.

    PubMed

    Ueda, Kyoko; Kawabata, Ryoko; Irie, Takashi; Nakai, Yoshiaki; Tohya, Yukinobu; Sakaguchi, Takemasa

    2013-01-01

    Tannins, plant-derived polyphenols and other related compounds, have been utilized for a long time in many fields such as the food industry and manufacturing. In this study, we investigated the anti-viral effects of tannins on 12 different viruses including both enveloped viruses (influenza virus H3N2, H5N3, herpes simplex virus-1, vesicular stomatitis virus, Sendai virus and Newcastle disease virus) and non-enveloped viruses (poliovirus, coxsachievirus, adenovirus, rotavirus, feline calicivirus and mouse norovirus). We found that extracts from persimmon (Diospyros kaki), which contains ca. 22% of persimmon tannin, reduced viral infectivity in more than 4-log scale against all of the viruses tested, showing strong anti-viral effects against a broad range of viruses. Other tannins derived from green tea, acacia and gallnuts were effective for some of the viruses, while the coffee extracts were not effective for any of the virus. We then investigated the mechanism of the anti-viral effects of persimmon extracts by using mainly influenza virus. Persimmon extracts were effective within 30 seconds at a concentration of 0.25% and inhibited attachment of the virus to cells. Pretreatment of cells with the persimmon extracts before virus infection or post-treatment after virus infection did not inhibit virus replication. Protein aggregation seems to be a fundamental mechanism underlying the anti-viral effect of persimmon tannin, since viral proteins formed aggregates when purified virions were treated with the persimmon extracts and since the anti-viral effect was competitively inhibited by a non-specific protein, bovine serum albumin. Considering that persimmon tannin is a food supplement, it has a potential to be utilized as a safe and highly effective anti-viral reagent against pathogenic viruses.

  10. Inactivation of pathogenic viruses by plant-derived tannins: strong effects of extracts from persimmon (Diospyros kaki) on a broad range of viruses.

    PubMed

    Ueda, Kyoko; Kawabata, Ryoko; Irie, Takashi; Nakai, Yoshiaki; Tohya, Yukinobu; Sakaguchi, Takemasa

    2013-01-01

    Tannins, plant-derived polyphenols and other related compounds, have been utilized for a long time in many fields such as the food industry and manufacturing. In this study, we investigated the anti-viral effects of tannins on 12 different viruses including both enveloped viruses (influenza virus H3N2, H5N3, herpes simplex virus-1, vesicular stomatitis virus, Sendai virus and Newcastle disease virus) and non-enveloped viruses (poliovirus, coxsachievirus, adenovirus, rotavirus, feline calicivirus and mouse norovirus). We found that extracts from persimmon (Diospyros kaki), which contains ca. 22% of persimmon tannin, reduced viral infectivity in more than 4-log scale against all of the viruses tested, showing strong anti-viral effects against a broad range of viruses. Other tannins derived from green tea, acacia and gallnuts were effective for some of the viruses, while the coffee extracts were not effective for any of the virus. We then investigated the mechanism of the anti-viral effects of persimmon extracts by using mainly influenza virus. Persimmon extracts were effective within 30 seconds at a concentration of 0.25% and inhibited attachment of the virus to cells. Pretreatment of cells with the persimmon extracts before virus infection or post-treatment after virus infection did not inhibit virus replication. Protein aggregation seems to be a fundamental mechanism underlying the anti-viral effect of persimmon tannin, since viral proteins formed aggregates when purified virions were treated with the persimmon extracts and since the anti-viral effect was competitively inhibited by a non-specific protein, bovine serum albumin. Considering that persimmon tannin is a food supplement, it has a potential to be utilized as a safe and highly effective anti-viral reagent against pathogenic viruses. PMID:23372851

  11. Evidence of Apis cerana Sacbrood virus Infection in Apis mellifera

    PubMed Central

    Gong, Hong-Ri; Chen, Xiu-Xian; Chen, Yan Ping; Hu, Fu-Liang; Zhang, Jiang-Lin; Lin, Zhe-Guang; Yu, Ji-Wei

    2016-01-01

    Sacbrood virus (SBV) is one of the most destructive viruses in the Asian honeybee Apis cerana but is much less destructive in Apis mellifera. In previous studies, SBV isolates infecting A. cerana (AcSBV) and SBV isolates infecting A. mellifera (AmSBV) were identified as different serotypes, suggesting a species barrier in SBV infection. In order to investigate this species isolation, we examined the presence of SBV infection in 318 A. mellifera colonies and 64 A. cerana colonies, and we identified the genotypes of SBV isolates. We also performed artificial infection experiments under both laboratory and field conditions. The results showed that 38 A. mellifera colonies and 37 A. cerana colonies were positive for SBV infection. Phylogenetic analysis based on RNA-dependent RNA polymerase (RdRp) gene sequences indicated that A. cerana isolates and most A. mellifera isolates formed two distinct clades but two strains isolated from A. mellifera were clustered with the A. cerana isolates. In the artificial-infection experiments, AcSBV negative-strand RNA could be detected in both adult bees and larvae of A. mellifera, although there were no obvious signs of the disease, demonstrating the replication of AcSBV in A. mellifera. Our results suggest that AcSBV is able to infect A. mellifera colonies with low prevalence (0.63% in this study) and pathogenicity. This work will help explain the different susceptibilities of A. cerana and A. mellifera to sacbrood disease and is potentially useful for guiding beekeeping practices. PMID:26801569

  12. Presence of Pathogenic Bacteria and Viruses in the Daycare Environment.

    PubMed

    Ibfelt, Tobias; Engelund, Eva Hoy; Permin, Anders; Madsen, Jonas Stenløkke; Schultz, Anna Charlotte; Andersen, Leif Percival

    2015-10-01

    The number of children in daycare centers (DCCs) is rising. This increases exposure to microorganisms and infectious diseases. Little is known about which bacteria and viruses are present in the DCC environment and where they are located. In the study described in this article, the authors set out to determine the prevalence of pathogenic bacteria and viruses and to find the most contaminated fomites in DCCs. Fifteen locations in each DCC were sampled for bacteria, respiratory viruses, and gastrointestinal viruses. The locations were in the toilet, kitchen, and playroom areas and included nursery pillows, toys, and tables, among other things. Coliform bacteria were primarily found in the toilet and kitchen areas whereas nasopharyngeal bacteria were found mostly on toys and fabric surfaces in the playroom. Respiratory viruses were omnipresent in the DCC environment, especially on the toys.

  13. Presence of Pathogenic Bacteria and Viruses in the Daycare Environment.

    PubMed

    Ibfelt, Tobias; Engelund, Eva Hoy; Permin, Anders; Madsen, Jonas Stenløkke; Schultz, Anna Charlotte; Andersen, Leif Percival

    2015-10-01

    The number of children in daycare centers (DCCs) is rising. This increases exposure to microorganisms and infectious diseases. Little is known about which bacteria and viruses are present in the DCC environment and where they are located. In the study described in this article, the authors set out to determine the prevalence of pathogenic bacteria and viruses and to find the most contaminated fomites in DCCs. Fifteen locations in each DCC were sampled for bacteria, respiratory viruses, and gastrointestinal viruses. The locations were in the toilet, kitchen, and playroom areas and included nursery pillows, toys, and tables, among other things. Coliform bacteria were primarily found in the toilet and kitchen areas whereas nasopharyngeal bacteria were found mostly on toys and fabric surfaces in the playroom. Respiratory viruses were omnipresent in the DCC environment, especially on the toys. PMID:26591334

  14. Emergence of mammalian species-infectious and -pathogenic avian influenza H6N5 virus with no evidence of adaptation.

    PubMed

    Nam, Jeong-Hyun; Kim, Eun-Ha; Song, Daesub; Choi, Young Ki; Kim, Jeong-Ki; Poo, Haryoung

    2011-12-01

    The migratory waterfowl of the world are considered to be the natural reservoir of influenza A viruses. Of the 16 hemagglutinin subtypes of avian influenza viruses, the H6 subtype is commonly perpetuated in its natural hosts and is of concern due to its potential to be a precursor of highly pathogenic influenza viruses by reassortment. During routine influenza surveillance, we isolated an unconventional H6N5 subtype of avian influenza virus. Experimental infection of mice revealed that this isolate replicated efficiently in the lungs, subsequently spread systemically, and caused lethality. The isolate also productively infected ferrets, with direct evidence of contact transmission, but no disease or transmission was seen in pigs. Although the isolate possessed the conserved receptor-binding site sequences of avian influenza viruses, it exhibited relatively low replication efficiencies in ducks and chickens. Our genetic and molecular analyses of the isolate revealed that its PB1 sequence showed the highest evolutionary relationship to those of highly pathogenic H5N1 avian influenza viruses and that its PA protein had an isoleucine residue at position 97 (a representative virulence marker). Further studies will be required to examine why our isolate has the virologic characteristics of mammalian influenza viruses but the archetypal receptor binding profiles of avian influenza viruses, as well as to determine whether its potential virulence markers (PB1 analogous to those of H5N1 viruses or isoleucine residue at position 97 within PA) could render it highly pathogenic in mice. PMID:21994462

  15. DIESEL EXHAUST ENHANCES INFLUENZA VIRUS INFECTIONS IN RESPIRATORY EPITHELIAL CELLS

    EPA Science Inventory

    Several factors, such as age and nutritional status can affect the susceptibility to influenza infections. Moreover, exposure to air pollutants, such as diesel exhaust (DE), has been shown to affect respiratory virus infections in rodent models. Influenza virus primarily infects ...

  16. Experimental infection with Brazilian Newcastle disease virus strain in pigeons and chickens

    PubMed Central

    Carrasco, Adriano de Oliveira Torres; Seki, Meire Christina; Benevenute, Jyan Lucas; Ikeda, Priscila; Pinto, Aramis Augusto

    2016-01-01

    This study was designed with the goal of adding as much information as possible about the role of pigeons (Columba livia) and chickens (Gallus gallus) in Newcastle disease virus epidemiology. These species were submitted to direct experimental infection with Newcastle disease virus to evaluate interspecies transmission and virus-host relationships. The results obtained in four experimental models were analyzed by hemagglutination inhibition and reverse transcriptase polymerase chain reaction for detection of virus shedding. These techniques revealed that both avian species, when previously immunized with a low pathogenic Newcastle disease virus strain (LaSota), developed high antibody titers that significantly reduced virus shedding after infection with a highly pathogenic Newcastle disease virus strain (São Joao do Meriti) and that, in chickens, prevent clinical signs. Infected pigeons shed the pathogenic strain, which was not detected in sentinel chickens or control birds. When the presence of Newcastle disease virus was analyzed in tissue samples by RT-PCR, in both species, the virus was most frequently found in the spleen. The vaccination regimen can prevent clinical disease in chickens and reduce viral shedding by chickens or pigeons. Biosecurity measures associated with vaccination programs are crucial to maintain a virulent Newcastle disease virus-free status in industrial poultry in Brazil. PMID:26887250

  17. Experimental infection with Brazilian Newcastle disease virus strain in pigeons and chickens.

    PubMed

    Carrasco, Adriano de Oliveira Torres; Seki, Meire Christina; Benevenute, Jyan Lucas; Ikeda, Priscila; Pinto, Aramis Augusto

    2016-01-01

    This study was designed with the goal of adding as much information as possible about the role of pigeons (Columba livia) and chickens (Gallus gallus) in Newcastle disease virus epidemiology. These species were submitted to direct experimental infection with Newcastle disease virus to evaluate interspecies transmission and virus-host relationships. The results obtained in four experimental models were analyzed by hemagglutination inhibition and reverse transcriptase polymerase chain reaction for detection of virus shedding. These techniques revealed that both avian species, when previously immunized with a low pathogenic Newcastle disease virus strain (LaSota), developed high antibody titers that significantly reduced virus shedding after infection with a highly pathogenic Newcastle disease virus strain (São Joao do Meriti) and that, in chickens, prevent clinical signs. Infected pigeons shed the pathogenic strain, which was not detected in sentinel chickens or control birds. When the presence of Newcastle disease virus was analyzed in tissue samples by RT-PCR, in both species, the virus was most frequently found in the spleen. The vaccination regimen can prevent clinical disease in chickens and reduce viral shedding by chickens or pigeons. Biosecurity measures associated with vaccination programs are crucial to maintain a virulent Newcastle disease virus-free status in industrial poultry in Brazil.

  18. Viral dynamics in hepatitis B virus infection.

    PubMed Central

    Nowak, M A; Bonhoeffer, S; Hill, A M; Boehme, R; Thomas, H C; McDade, H

    1996-01-01

    Treatment of chronic hepatitis B virus (HBV) infections with the reverse transcriptase inhibitor lamivudine leads to a rapid decline in plasma viremia and provides estimates for crucial kinetic constants of HBV replication. We find that in persistently infected patients, HBV particles are cleared from the plasma with a half-life of approximately 1.0 day, which implies a 50% daily turnover of the free virus population. Total viral release into the periphery is approximately 10(11) virus particles per day. Although we have no direct measurement of the infected cell mass, we can estimate the turnover rate of these cells in two ways: (i) by comparing the rate of viral production before and after therapy or (ii) from the decline of hepatitis B antigen during treatment. These two independent methods give equivalent results: we find a wide distribution of half-lives for virus-producing cells, ranging from 10 to 100 days in different patients, which may reflect differences in rates of lysis of infected cells by immune responses. Our analysis provides a quantitative understanding of HBV replication dynamics in vivo and has implications for the optimal timing of drug treatment and immunotherapy in chronic HBV infection. This study also represents a comparison for recent findings on the dynamics of human immunodeficiency virus (HIV) infection. The total daily production of plasma virus is, on average, higher in chronic HBV carriers than in HIV-infected patients, but the half-life of virus-producing cells is much shorter in HIV. Most strikingly, there is no indication of drug resistance in HBV-infected patients treated for up to 24 weeks. PMID:8633078

  19. Highly pathogenic avian influenza virus among wild birds in Mongolia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The central Asian country of Mongolia supports large populations of migratory water birds that migrate across much of Asia where highly pathogenic avian influenza (HPAI) virus subtype H5N1 is endemic. This, together with the near absence of domestic poultry, makes Mongolia an ideal location to unde...

  20. Rapidly expanding range of highly pathogenic avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The recent introduction of highly pathogenic avian influenza virus (HPAIV) H5N8 into Europe and North America poses significant risks to poultry industries and wildlife populations and warrants continued and heightened vigilance. First discovered in South Korean poultry and wild birds in early 2014...

  1. Assessing microbial decontamination of indoor air with particular focus on human pathogenic viruses.

    PubMed

    Duchaine, Caroline

    2016-09-01

    Transmission of bacterial, fungal, and viral pathogens is of primary importance in public and occupational health and infection control. Although several standardized protocols have been proposed to target microbes on fomites through surface decontamination, use of microbicidal agents, and cleaning processes, only limited guidance is available on microbial decontamination of indoor air to reduce the risk of pathogen transmission between individuals. This article reviews the salient aspects of airborne transmission of infectious agents, exposure assessment, in vitro assessment of microbicidal agents, and processes for air decontamination for infection prevention and control. Laboratory-scale testing (eg, rotating chambers, wind tunnels) and promising field-scale methodologies to decontaminate indoor air are also presented. The potential of bacteriophages as potential surrogates for the study of airborne human pathogenic viruses is also discussed.

  2. Assessing microbial decontamination of indoor air with particular focus on human pathogenic viruses.

    PubMed

    Duchaine, Caroline

    2016-09-01

    Transmission of bacterial, fungal, and viral pathogens is of primary importance in public and occupational health and infection control. Although several standardized protocols have been proposed to target microbes on fomites through surface decontamination, use of microbicidal agents, and cleaning processes, only limited guidance is available on microbial decontamination of indoor air to reduce the risk of pathogen transmission between individuals. This article reviews the salient aspects of airborne transmission of infectious agents, exposure assessment, in vitro assessment of microbicidal agents, and processes for air decontamination for infection prevention and control. Laboratory-scale testing (eg, rotating chambers, wind tunnels) and promising field-scale methodologies to decontaminate indoor air are also presented. The potential of bacteriophages as potential surrogates for the study of airborne human pathogenic viruses is also discussed. PMID:27590696

  3. Pathogenicity and transmissibility of reassortant H9 influenza viruses with genes from pandemic H1N1 virus.

    PubMed

    Qiao, Chuanling; Liu, Qinfang; Bawa, Bhupinder; Shen, Huigang; Qi, Wenbao; Chen, Ying; Mok, Chris Ka Pun; García-Sastre, Adolfo; Richt, Jürgen A; Ma, Wenjun

    2012-11-01

    Both H9N2 avian influenza and 2009 pandemic H1N1 viruses (pH1N1) are able to infect humans and swine, which has raised concerns that novel reassortant H9 viruses with pH1N1 genes might be generated in these hosts by reassortment. Although previous studies have demonstrated that reassortant H9 viruses with pH1N1 genes show increased virulence in mice and transmissibility in ferrets, the virulence and transmissibility of reassortant H9 viruses in natural hosts such as chickens and swine remain unknown. This study generated two reassortant H9 viruses (H9N2/CA09 and H9N1/CA09) in the background of the pH1N1 A/California/04/2009 (CA09) virus by replacing either both the haemagglutinin (HA) and neuraminidase (NA) genes or only the HA gene with the respective genes from the A/quail/Hong Kong/G1/1997 (H9N2) virus and evaluated their replication, pathogenicity and transmission in chickens and pigs compared with the parental viruses. Chickens that were infected with the parental H9N2 and reassortant H9 viruses seroconverted. The parental H9N2 and reassortant H9N2/CA09 viruses were transmitted to sentinel chickens, but H9N1/CA09 virus was not. The parental H9N2 replicated poorly and was not transmitted in pigs, whereas both H9N2/CA09 and H9N1/CA09 viruses replicated and were transmitted efficiently in pigs, similar to the pH1N1 virus. These results demonstrated that reassortant H9 viruses with pH1N1 genes show enhanced replication and transmissibility in pigs compared with the parental H9N2 virus, indicating that they may pose a threat for humans if such reassortants arise in swine.

  4. Respiratory syncytial virus infection in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine respiratory syncytial virus (bRSV) is a cause of respiratory disease in cattle world-wide. It has an integral role in enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bRSV infection can predispose calves to secondary bacterial infection by org...

  5. Pseudotyping of vesicular stomatitis virus with the envelope glycoproteins of highly pathogenic avian influenza viruses.

    PubMed

    Zimmer, Gert; Locher, Samira; Berger Rentsch, Marianne; Halbherr, Stefan J

    2014-08-01

    Pseudotype viruses are useful for studying the envelope proteins of harmful viruses. This work describes the pseudotyping of vesicular stomatitis virus (VSV) with the envelope glycoproteins of highly pathogenic avian influenza viruses. VSV lacking the homotypic glycoprotein (G) gene (VSVΔG) was used to express haemagglutinin (HA), neuraminidase (NA) or the combination of both. Propagation-competent pseudotype viruses were only obtained when HA and NA were expressed from the same vector genome. Pseudotype viruses containing HA from different H5 clades were neutralized specifically by immune sera directed against the corresponding clade. Fast and sensitive reading of test results was achieved by vector-mediated expression of GFP. Pseudotype viruses expressing a mutant VSV matrix protein showed restricted spread in IFN-competent cells. This pseudotype system will facilitate the detection of neutralizing antibodies against virulent influenza viruses, circumventing the need for high-level biosafety containment.

  6. Transcriptomic analysis of responses to infectious salmon anemia virus infection in macrophage-like cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aquatic orthomyxovirus infectious salmon anemia virus (ISAV) is an important pathogen for salmonid aquaculture, however little is known about protective and pathological host responses to infection. We have investigated intracellular responses during cytopathic ISAV infection in the macrophage-l...

  7. Bovine viral diarrhea virus infection induces autophagy in MDBK cells.

    PubMed

    Fu, Qiang; Shi, Huijun; Ren, Yan; Guo, Fei; Ni, Wei; Qiao, Jun; Wang, Pengyan; Zhang, Hui; Chen, Chuangfu

    2014-07-01

    Bovine viral diarrhea virus (BVDV) is an enveloped, positive-sense, single-stranded RNA virus that belongs to the genus Pestivirus (Flaviviridae). The signaling pathways and levels of signaling molecules are altered in Madin-Darby Bovine Kidney (MDBK) cells infected with BVDV. Autophagy is a conservative biological degradation pathway that mainly eliminates and degrades damaged or superfluous organelles and macromolecular complexes for intracellular recycling in eukaryotic cells. Autophagy can also be induced as an effective response to maintain cellular homeostasis in response to different stresses, such as nutrient or growth factor deprivation, hypoxia, reactive oxygen species exposure and pathogen infection. However, the effects of BVDV infection on autophagy in MDBK cells remain unclear. Therefore, we performed an analysis of autophagic activity after BVDV NADL infection using real-time PCR, electron microscopy, laser confocal microscopy, and Western blotting analysis. The results demonstrated that BVDV NADL infection increased autophagic activity and significantly elevated the expression levels of the autophagy-related genes Beclin1 and ATG14 in MDBK cells. However, the knockdown of Beclin1 and ATG14 by RNA interference (RNAi) did not affect BVDV NADL infection-related autophagic activity. These findings provided a novel perspective to elaborate the effects of viral infection on the host cells.

  8. Pathogenicity and immunogenicity of different recombinant Newcastle disease virus clone 30 variants after in ovo vaccination.

    PubMed

    Ramp, Kristina; Topfstedt, Eylin; Wäckerlin, Regula; Höper, Dirk; Ziller, Mario; Mettenleiter, Thomas C; Grund, Christian; Römer-Oberdörfer, Angela

    2012-03-01

    Even though Newcastle disease virus (NDV) live vaccine strains can be applied to 1-day-old chickens, they are pathogenic to chicken embryos when given in ovo 3 days before hatch. Based on the reverse genetics system, we modified recombinant NDV (rNDV) established from lentogenic vaccine strain Clone 30 by introducing specific mutations within the fusion (F) and hemagglutinin-neuraminidase (HN) proteins, which have recently been suggested as being responsible for attenuation of selected vaccine variants (Mast et al. Vaccine 24:1756-1765, 2006) resulting in rNDV49. Another recombinant (rNDVGu) was generated to correct sequence differences between rNDV and vaccine strain NDV Clone 30. Recombinant viruses rNDV, rNDV49, and rNDVGu have reduced virulence compared with NDV Clone 30, represented by lower intracerebral pathogenicity indices and elevated mean death time. After in ovo inoculation, hatchability was comparable for all infected groups. However, only one chicken from the NDV Clone 30 group survived a 21-day observation period; whereas, the survival rate of hatched chicks from groups receiving recombinant NDV was between 40% and 80%, with rNDVGu being the most pathogenic virus. Furthermore, recombinant viruses induced protection against challenge infection with virulent NDV 21 days post hatch. Differences in antibody response of recombinant viruses indicate that immunogenicity is correlated to virulence. In summary, our data show that point mutations can reduce virulence of NDV. However, alteration of specific amino acids in F and HN proteins of rNDV did not lead to further attenuation as indicated by their pathogenicity for chicken after in ovo inoculation.

  9. Bronchointerstitial pneumonia in guinea pigs following inoculation with H5N1 high pathogenicity avian influenza virus.

    PubMed

    Kwon, Y K; Lipatov, A S; Swayne, D E

    2009-01-01

    The H5N1 high-pathogenicity avian influenza (HPAI) viruses have caused widespread disease of poultry in Asia, Africa and the Middle East, and sporadic human infections. The guinea pig model has been used to study human H3N2 and H1N1 influenza viruses, but knowledge is lacking on H5N1 HPAI virus infections. Guinea pigs were inoculated intranasally or intragastrically with A/Vietnam/1203/04 (VN/04) or A/Muscovy duck/Vietnam/209/05 (MDk/VN/05) viruses. Mild listlessness was seen at 2 and 3 days postinoculation (DPI) in guinea pigs inoculated intranasally with VN/04 virus. At 5 DPI, the guinea pigs had bronchointerstitial pneumonia and virus was identified in bronchiolar epithelium and alveolar macrophages. Virus was isolated from the lungs but was lacking from other organs. Minimal lung lesions were seen in intranasal MDk/VN/06 group and virus was not detected, but serologic evidence of infection was observed. Intragastric exposure failed to produce infection or lesions with either virus. The localized respiratory disease in guinea pigs with H5N1 viruses was very similar to that of H3N2 and H1N1 influenza in humans and was less severe than reported for H5N1 human cases.

  10. Evidence of the synergistic interaction of honey bee pathogens Nosema ceranae and Deformed wing virus.

    PubMed

    Zheng, Huo-Qing; Gong, Hong-Ri; Huang, Shao-Kang; Sohr, Alex; Hu, Fu-Liang; Chen, Yan Ping

    2015-05-15

    Nosema ceranae and Deformed wing virus (DWV) are two of the most prevalent pathogens currently attacking Western honey bees, Apis mellifera, and often simultaneously infect the same hosts. Here we investigated the effect of N. ceranae and Deformed wing virus (DWV) interactions on infected honey bees under lab conditions and at different nutrition statuses. Our results showed that Nosema could accelerate DWV replication in infected bees in a dose-dependent manner at the early stages of DWV infection. When bees were restricted from pollen nutrition, inoculation with 1×10(4) and 1×10(5) spores/bee could cause a significant increase in DWV titer, while inoculation with 1×10(3) spores/bee did not show any significant effect on the DWV titer. When bees were provided with pollen, only inoculation with 1×10(5) spores/bee showed significant effect on DWV titer. However, our results also showed that the two pathogens did not act synergistically when the titer of DWV reached a plateau. This study suggests that the synergistic effect of N. ceranae and DWV is dosage- and nutrition-dependent and that the synergistic interactions between the two pathogens could have implications on honey bee colony losses. PMID:25752367

  11. Evidence of the synergistic interaction of honey bee pathogens Nosema ceranae and Deformed wing virus.

    PubMed

    Zheng, Huo-Qing; Gong, Hong-Ri; Huang, Shao-Kang; Sohr, Alex; Hu, Fu-Liang; Chen, Yan Ping

    2015-05-15

    Nosema ceranae and Deformed wing virus (DWV) are two of the most prevalent pathogens currently attacking Western honey bees, Apis mellifera, and often simultaneously infect the same hosts. Here we investigated the effect of N. ceranae and Deformed wing virus (DWV) interactions on infected honey bees under lab conditions and at different nutrition statuses. Our results showed that Nosema could accelerate DWV replication in infected bees in a dose-dependent manner at the early stages of DWV infection. When bees were restricted from pollen nutrition, inoculation with 1×10(4) and 1×10(5) spores/bee could cause a significant increase in DWV titer, while inoculation with 1×10(3) spores/bee did not show any significant effect on the DWV titer. When bees were provided with pollen, only inoculation with 1×10(5) spores/bee showed significant effect on DWV titer. However, our results also showed that the two pathogens did not act synergistically when the titer of DWV reached a plateau. This study suggests that the synergistic effect of N. ceranae and DWV is dosage- and nutrition-dependent and that the synergistic interactions between the two pathogens could have implications on honey bee colony losses.

  12. Endogenous tick viruses and modulation of tick-borne pathogen growth

    PubMed Central

    Bell-Sakyi, Lesley; Attoui, Houssam

    2013-01-01

    Ticks transmit a wide range of viral, bacterial and protozoan pathogens, many of which can establish persistent infections of lifelong duration in the vector tick and in some cases are transmitted transovarially to the next generation. In addition many ixodid and argasid tick cell lines and, by inference the parent ticks from which they were derived, harbor endogenous viruses (ETV) of which almost nothing is known. In general, low level persistent infections with viral pathogens (arboviruses) are not known to have a deleterious effect on tick survival and fitness, suggesting that they can strike a balance with the tick innate immune response. This tolerance of arbovirus infection may be modulated by the permanent presence of ETV in the host cell. In mosquito cells, temporary or permanent silencing of the genes of an endogenous virus by RNA interference can result in changes in replication rate of a co-infecting arbovirus. We propose that tick cell lines offer a useful model system for in vitro investigation of the modulatory effect of ETV on superinfecting pathogen survival and replication in ticks, using the molecular manipulation techniques applied to insect cells. PMID:23875176

  13. Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer's Disease.

    PubMed

    Harris, Steven A; Harris, Elizabeth A

    2015-01-01

    This review focuses on research in epidemiology, neuropathology, molecular biology, and genetics regarding the hypothesis that pathogens interact with susceptibility genes and are causative in sporadic Alzheimer's disease (AD). Sporadic AD is a complex multifactorial neurodegenerative disease with evidence indicating coexisting multi-pathogen and inflammatory etiologies. There are significant associations between AD and various pathogens, including Herpes simplex virus type 1 (HSV-1), Cytomegalovirus, and other Herpesviridae, Chlamydophila pneumoniae, spirochetes, Helicobacter pylori, and various periodontal pathogens. These pathogens are able to evade destruction by the host immune system, leading to persistent infection. Bacterial and viral DNA and RNA and bacterial ligands increase the expression of pro-inflammatory molecules and activate the innate and adaptive immune systems. Evidence demonstrates that pathogens directly and indirectly induce AD pathology, including amyloid-β (Aβ) accumulation, phosphorylation of tau protein, neuronal injury, and apoptosis. Chronic brain infection with HSV-1, Chlamydophila pneumoniae, and spirochetes results in complex processes that interact to cause a vicious cycle of uncontrolled neuroinflammation and neurodegeneration. Infections such as Cytomegalovirus, Helicobacter pylori, and periodontal pathogens induce production of systemic pro-inflammatory cytokines that may cross the blood-brain barrier to promote neurodegeneration. Pathogen-induced inflammation and central nervous system accumulation of Aβ damages the blood-brain barrier, which contributes to the pathophysiology of AD. Apolipoprotein E4 (ApoE4) enhances brain infiltration by pathogens including HSV-1 and Chlamydophila pneumoniae. ApoE4 is also associated with an increased pro-inflammatory response by the immune system. Potential antimicrobial treatments for AD are discussed, including the rationale for antiviral and antibiotic clinical trials.

  14. Hepatitis C Virus Infection in HIV-infected Patients.

    PubMed

    Sulkowski, Mark S.

    2001-10-01

    The hepatitis C virus (HCV) is a spherical enveloped RNA virus of the Flaviviridae family, classified within the Hepacivirus genus. Since its discovery in 1989, HCV has been recognized as a major cause of chronic hepatitis and hepatic fibrosis that progresses in some patients to cirrhosis and hepatocellular carcinoma. In the United States, approximately 4 million people have been infected with HCV, and 10,000 HCV-related deaths occur each year. Due to shared routes of transmission, HCV and HIV co-infection are common, affecting approximately one third of all HIV-infected persons in the United States. In addition, HIV co-infection is associated with higher HCV RNA viral load and a more rapid progression of HCV-related liver disease, leading to an increased risk of cirrhosis. HCV infection may also impact the course and management of HIV disease, particularly by increasing the risk of antiretroviral drug-induced hepatotoxicity. Thus, chronic HCV infection acts as an opportunistic disease in HIV-infected persons because the incidence of infection is increased and the natural history of HCV infection is accelerated in co-infected persons. Strategies to prevent primary HCV infection and to modify the progression of HCV-related liver disease are urgently needed among HIV/HCV co-infected individuals.

  15. Hepatitis C virus infection in HIV-infected patients.

    PubMed

    Sulkowski, Mark S

    2007-10-01

    The hepatitis C virus (HCV) is a spherical enveloped RNA virus of the Flaviviridae family, classified within the Hepacivirus genus. Since its discovery in 1989, HCV has been recognized as a major cause of chronic hepatitis and hepatic fibrosis that progresses in some patients to cirrhosis and hepatocellular carcinoma. In the United States, approximately 4 million people have been infected with HCV, and 10,000 HCVrelated deaths occur each year. Due to shared routes of transmission, HCV and HIV co-infection are common, affecting approximately one third of all HIV-infected persons in the United States. In addition, HIV co-infection is associated with higher HCV RNA viral load and a more rapid progression of HCV-related liver disease, leading to an increased risk of cirrhosis. HCV infection may also impact the course and management of HIV disease, particularly by increasing the risk of antiretroviral drug-induced hepatotoxicity. Thus, chronic HCV infection acts as an opportunistic disease in HIV-infected persons because the incidence of infection is increased and the natural history of HCV infection is accelerated in co-infected persons. Strategies to prevent primary HCV infection and to modify the progression of HCV-related liver disease are urgently needed among HIV/HCV co-infected individuals.

  16. Expression of Factor X in BHK-21 Cells Promotes Low Pathogenic Influenza Viruses Replication.

    PubMed

    Shahsavandi, Shahla; Ebrahimi, Mohammad Majid; Masoudi, Shahin; Izadi, Hasan

    2015-01-01

    A cDNA clone for factor 10 (FX) isolated from chicken embryo inserted into the mammalian cell expression vector pCDNA3.1 was transfected into the baby hamster kidney (BHK-21) cell line. The generated BHK-21 cells with inducible expression of FX were used to investigate the efficacy of the serine transmembrane protease to proteolytic activation of influenza virus hemagglutinin (HA) with monobasic cleavage site. Data showed that the BHK-21/FX stably expressed FX after ten serial passages. The cells could proteolytically cleave the HA of low pathogenic avian influenza virus at multiplicity of infection 0.01. Growth kinetics of the virus on BHK-21/FX, BHK-21, and MDCK cells were evaluated by titrations of virus particles in each culture supernatant. Efficient multicycle viral replication was markedly detected in the cell at subsequent passages. Virus titration demonstrated that BHK-21/FX cell supported high-titer growth of the virus in which the viral titer is comparable to the virus grown in BHK-21 or MDCK cells with TPCK-trypsin. The results indicate potential application for the BHK-21/FX in influenza virus replication procedure and related studies.

  17. [Effect of Deletion of the Carboxyl Terminal of the NS1 Protein on Pathogenicity of the Influenza B Virus].

    PubMed

    Li, Xue; Yu, Zhijun; Sun, Weiyang; Chen, Qiang; Wang, Tiecheng; Yang, Songtao; Huang, Geng; Gao, Yuwei; Xia, Xianzhu; Zhang, Xuemei

    2015-07-01

    To analyze the molecular basis of the variation of the pathogenicity of the influenza B virus, we rescued a recombinant virus with a deletion in the carboxyl terminal of the NS1 protein using reverse genetics based on the parental virus B-S9 of B/Yamagata/16/88. A mutant strain with a deletion of 171 amino acids in the carboxyl terminal of the NS1 protein was named "B-L5". BALB/c mice were inoculated with 3 X 105 EID50 of B-L5 and the parental virus B-S9, respectively. Then, weight changes, survival, and viral titers were documented. During 3 days post-inoculation (dpi) to 7 dpi, the weight of mice infected with B-S9 decreased. However, the weight of mice infected with B-L5 showed weight decreases only at 2 dpi, and quickly recovered at 3 dpi. B-S9 and B-L5 could replicate in the lungs of BALB/c mice. However, viral titers in the lungs of mice infected with B-L5 were 7900-times lower than those of mice infected with B-S9 at 3 dpi. Viral titers in the lungs of mice infected with B-L5 were not detected at 6 dpi. These results showed that, compared with the parent virus B-S9, the mutant virus B-L5 showed lower pathogenicity in BALB/c mice. Our study suggests that deletion of the carboxyl terminal of the NS1 protein decreases the pathogenicity of the influenza B virus. Establishment of a reverse-genetics system for the B influenza virus will provide a platform for studying its pathogenesis, and mechanism of transmission, and for developing live-attenuated influenza B virus vaccines. PMID:26524913

  18. 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

  19. Pathogenicity in domestic ducks and mice of highly pathogenic H5N1 clade 2.3.2.1 influenza viruses recently circulating in Eastern Asia.

    PubMed

    Kang, Hyun-Mi; Choi, Jun-Gu; Kim, Kwang-Il; Kim, Bang-Sil; Batchuluun, Damdinjav; Erdene-Ochir, Tseren-Ochir; Kim, Min-Chul; Kwon, Jun-Hun; Park, Choi-Kyu; Lee, Youn-Jeong

    2013-12-27

    Influenza virus A (H5N1) clade 2.3.2.1 has recently caused widespread outbreaks of disease in domestic poultry and wild birds in Eastern Asia. In the current study, the antigenicity and pathogenicity of three clade 2.3.2.1 viruses (Ck/Kr/Gimje/08, Ws/Mongolia/1/09, and Ws/Mongolia/7/10) were investigated in domestic ducks and mice. The H5N1 influenza viruses in this study were antigenically similar to each other (r-values of 0.35-1.4). The three viruses replicated systemically in all tissues tested in domestic ducks, indicating high pathogenicity. However, the viruses produced different clinical signs and mortality rates: Ck/Kr/Gimje/08 and Ws/Mongolia/1/09 resulted in 100% mortality with severe neurological signs, whereas Ws/Mongolia/7/10 resulted in 50% mortality with relatively mild neurological signs. In mice, infection with Ck/Kr/Gimje/08 and Ws/Mongolia/7/10 resulted in weight loss that peaked at 4 days post-infection (22.3% and 20.8%, respectively), same MLD50 (2.2 Log10 EID50) and systemic replication. The three viruses had K deletion at the -2 position of the HA1-connecting peptide (PQRERRRK-R), which is associated with increased virulence in domestic ducks and harbored NA stalk deletion, NS1 deletion and mutation of P42S in NS1, and full length (90aa) in PB1-F2, which confer increased virulence in mice. Our study shows that clade 2.3.2.1 viruses from Korea and Mongolia are antigenically similar and highly pathogenic in both domestic ducks and mice. Moreover, we provide molecular determinants of the clade 2.3.2.1 viruses associated with the pathogenicity in domestic ducks and mice, respectively.

  20. A Single Amino Acid in the M1 Protein Responsible for the Different Pathogenic Potentials of H5N1 Highly Pathogenic Avian Influenza Virus Strains

    PubMed Central

    Nao, Naganori; Kajihara, Masahiro; Manzoor, Rashid; Maruyama, Junki; Yoshida, Reiko; Muramatsu, Mieko; Miyamoto, Hiroko; Igarashi, Manabu; Eguchi, Nao; Sato, Masahiro; Kondoh, Tatsunari; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Kida, Hiroshi; Takada, Ayato

    2015-01-01

    Two highly pathogenic avian influenza virus strains, A/duck/Hokkaido/WZ83/2010 (H5N1) (WZ83) and A/duck/Hokkaido/WZ101/2010 (H5N1) (WZ101), which were isolated from wild ducks in Japan, were found to be genetically similar, with only two amino acid differences in their M1 and PB1 proteins at positions 43 and 317, respectively. We found that both WZ83 and WZ101 caused lethal infection in chickens but WZ101 killed them more rapidly than WZ83. Interestingly, ducks experimentally infected with WZ83 showed no or only mild clinical symptoms, whereas WZ101 was highly lethal. We then generated reassortants between these viruses and found that exchange of the M gene segment completely switched the pathogenic phenotype in both chickens and ducks, indicating that the difference in the pathogenicity for these avian species between WZ83 and WZ101 was determined by only a single amino acid in the M1 protein. It was also found that WZ101 showed higher pathogenicity than WZ83 in mice and that WZ83, whose M gene was replaced with that of WZ101, showed higher pathogenicity than wild-type WZ83, although this reassortant virus was not fully pathogenic compared to wild-type WZ101. These results suggest that the amino acid at position 43 of the M1 protein is one of the factors contributing to the pathogenicity of H5N1 highly pathogenic avian influenza viruses in both avian and mammalian hosts. PMID:26368015

  1. Pathogenic Differences between Nipah Virus Bangladesh and Malaysia Strains in Primates: Implications for Antibody Therapy.

    PubMed

    Mire, Chad E; Satterfield, Benjamin A; Geisbert, Joan B; Agans, Krystle N; Borisevich, Viktoriya; Yan, Lianying; Chan, Yee-Peng; Cross, Robert W; Fenton, Karla A; Broder, Christopher C; Geisbert, Thomas W

    2016-01-01

    Nipah virus (NiV) is a paramyxovirus that causes severe disease in humans and animals. There are two distinct strains of NiV, Malaysia (NiVM) and Bangladesh (NiVB). Differences in transmission patterns and mortality rates suggest that NiVB may be more pathogenic than NiVM. To investigate pathogenic differences between strains, 4 African green monkeys (AGM) were exposed to NiVM and 4 AGMs were exposed to NiVB. While NiVB was uniformly lethal, only 50% of NiVM-infected animals succumbed to infection. Histopathology of lungs and spleens from NiVB-infected AGMs was significantly more severe than NiVM-infected animals. Importantly, a second study utilizing 11 AGMs showed that the therapeutic window for human monoclonal antibody m102.4, previously shown to rescue AGMs from NiVM infection, was much shorter in NiVB-infected AGMs. Together, these data show that NiVB is more pathogenic in AGMs under identical experimental conditions and suggests that postexposure treatments may need to be NiV strain specific for optimal efficacy. PMID:27484128

  2. Pathogenic Differences between Nipah Virus Bangladesh and Malaysia Strains in Primates: Implications for Antibody Therapy

    PubMed Central

    Mire, Chad E.; Satterfield, Benjamin A.; Geisbert, Joan B.; Agans, Krystle N.; Borisevich, Viktoriya; Yan, Lianying; Chan, Yee-Peng; Cross, Robert W.; Fenton, Karla A.; Broder, Christopher C.; Geisbert, Thomas W.

    2016-01-01

    Nipah virus (NiV) is a paramyxovirus that causes severe disease in humans and animals. There are two distinct strains of NiV, Malaysia (NiVM) and Bangladesh (NiVB). Differences in transmission patterns and mortality rates suggest that NiVB may be more pathogenic than NiVM. To investigate pathogenic differences between strains, 4 African green monkeys (AGM) were exposed to NiVM and 4 AGMs were exposed to NiVB. While NiVB was uniformly lethal, only 50% of NiVM-infected animals succumbed to infection. Histopathology of lungs and spleens from NiVB-infected AGMs was significantly more severe than NiVM-infected animals. Importantly, a second study utilizing 11 AGMs showed that the therapeutic window for human monoclonal antibody m102.4, previously shown to rescue AGMs from NiVM infection, was much shorter in NiVB-infected AGMs. Together, these data show that NiVB is more pathogenic in AGMs under identical experimental conditions and suggests that postexposure treatments may need to be NiV strain specific for optimal efficacy. PMID:27484128

  3. Phytohormone pathways as targets of pathogens to facilitate infection.

    PubMed

    Ma, Ka-Wai; Ma, Wenbo

    2016-08-01

    Plants are constantly threatened by potential pathogens. In order to optimize the output of defense against pathogens with distinct lifestyles, plants depend on hormonal networks to fine-tune specific responses and regulate growth-defense tradeoffs. To counteract, pathogens have evolved various strategies to disturb hormonal homeostasis and facilitate infection. Many pathogens synthesize plant hormones; more importantly, toxins and effectors are produced to manipulate hormonal crosstalk. Accumulating evidence has shown that pathogens exert extensive effects on plant hormone pathways not only to defeat immunity, but also modify habitat structure, optimize nutrient acquisition, and facilitate pathogen dissemination. In this review, we summarize mechanisms by which a wide array of pathogens gain benefits from manipulating plant hormone pathways.

  4. Sustained live poultry market surveillance contributes to early warnings for human infection with avian influenza viruses

    PubMed Central

    Fang, Shisong; Bai, Tian; Yang, Lei; Wang, Xin; Peng, Bo; Liu, Hui; Geng, Yijie; Zhang, Renli; Ma, Hanwu; Zhu, Wenfei; Wang, Dayan; Cheng, Jinquan; Shu, Yuelong

    2016-01-01

    Sporadic human infections with the highly pathogenic avian influenza (HPAI) A (H5N6) virus have been reported in different provinces in China since April 2014. From June 2015 to January 2016, routine live poultry market (LPM) surveillance was conducted in Shenzhen, Guangdong Province. H5N6 viruses were not detected until November 2015. The H5N6 virus-positive rate increased markedly beginning in December 2015, and viruses were detected in LPMs in all districts of the city. Coincidently, two human cases with histories of poultry exposure developed symptoms and were diagnosed as H5N6-positive in Shenzhen during late December 2015 and early January 2016. Similar viruses were identified in environmental samples collected in the LPMs and the patients. In contrast to previously reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or H7N9 viruses were detected in the present study. The increased H5N6 virus-positive rate in the LPMs and the subsequent human infections demonstrated that sustained LPM surveillance for avian influenza viruses provides an early warning for human infections. Interventions, such as LPM closures, should be immediately implemented to reduce the risk of human infection with the H5N6 virus when the virus is widely detected during LPM surveillance. PMID:27485495

  5. Sustained live poultry market surveillance contributes to early warnings for human infection with avian influenza viruses.

    PubMed

    Fang, Shisong; Bai, Tian; Yang, Lei; Wang, Xin; Peng, Bo; Liu, Hui; Geng, Yijie; Zhang, Renli; Ma, Hanwu; Zhu, Wenfei; Wang, Dayan; Cheng, Jinquan; Shu, Yuelong

    2016-01-01

    Sporadic human infections with the highly pathogenic avian influenza (HPAI) A (H5N6) virus have been reported in different provinces in China since April 2014. From June 2015 to January 2016, routine live poultry market (LPM) surveillance was conducted in Shenzhen, Guangdong Province. H5N6 viruses were not detected until November 2015. The H5N6 virus-positive rate increased markedly beginning in December 2015, and viruses were detected in LPMs in all districts of the city. Coincidently, two human cases with histories of poultry exposure developed symptoms and were diagnosed as H5N6-positive in Shenzhen during late December 2015 and early January 2016. Similar viruses were identified in environmental samples collected in the LPMs and the patients. In contrast to previously reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or H7N9 viruses were detected in the present study. The increased H5N6 virus-positive rate in the LPMs and the subsequent human infections demonstrated that sustained LPM surveillance for avian influenza viruses provides an early warning for human infections. Interventions, such as LPM closures, should be immediately implemented to reduce the risk of human infection with the H5N6 virus when the virus is widely detected during LPM surveillance. PMID:27485495

  6. Increased pathogenicity of rabies virus due to modification of a non-coding region.

    PubMed

    Virojanapirom, Phatthamon; Yamada, Kentaro; Khawplod, Pakamatz; Nishizono, Akira; Hemachudha, Thiravat

    2016-11-01

    Sub-passaging of QS-05, a street rabies virus (RABV) isolate, in non-neuronal cells resulted in a virus with higher pathogenicity, QS-BHK-P7. Four full-length cDNA plasmids were constructed and the corresponding recombinant viruses were recovered: rQS-05, rQS-BHK-P7 and rQS05-2475G/rQS-BHK-P7-2475A (made by switching of intergenic P-M between these two backbones). rQS-BHK-P7-2475 A virus had eight instead of seven adenosines in its poly(A) sequence. Interestingly, mutant viruses with 6 or 8 adenosines infected more neuroblastoma cells than their parental ones. Mice that were infected intracerebrally and intramuscularly with rQS05-2475G and rQS-BHK-P7 exhibited highest mortality. However, mice infected with rQS-BHK-P7-2475AA had the shortest survival time. This study demonstrates that modifications in the non-coding region may play a role in determining the virulence of RABV. PMID:27558122

  7. Airborne Transmission of Highly Pathogenic H7N1 Influenza Virus in Ferrets

    PubMed Central

    Finch, Courtney; Shao, Hongxia; Angel, Matthew; Chen, Hongjun; Capua, Ilaria; Cattoli, Giovanni; Monne, Isabella

    2014-01-01

    ABSTRACT Avian H7 influenza viruses are recognized as potential pandemic viruses, as personnel often become infected during poultry outbreaks. H7 infections in humans typically cause mild conjunctivitis; however, the H7N9 outbreak in the spring of 2013 has resulted in severe respiratory disease. To date, no H7 viruses have acquired the ability for sustained transmission among humans. Airborne transmission is considered a requirement for the emergence of pandemic influenza, and advanced knowledge of the molecular changes or signature required for transmission would allow early identification of pandemic vaccine seed stocks, screening and stockpiling of antiviral compounds, and eradication efforts focused on flocks harboring threatening viruses. Thus, we sought to determine if a highly pathogenic influenza A H7N1 (A/H7N1) virus with no history of human infection could become capable of airborne transmission among ferrets. We show that after 10 serial passages, A/H7N1 developed the ability to be transmitted to cohoused and airborne contact ferrets. Four amino acid mutations (PB2 T81I, NP V284M, and M1 R95K and Q211K) in the internal genes and a minimal amino acid mutation (K/R313R) in the stalk region of the hemagglutinin protein were associated with airborne transmission. Furthermore, transmission was not associated with loss of virulence. These findings highlight the importance of the internal genes in host adaptation and suggest that natural isolates carrying these mutations be further evaluated. Our results demonstrate that a highly pathogenic avian H7 virus can become capable of airborne transmission in a mammalian host, and they support ongoing surveillance and pandemic H7 vaccine development. IMPORTANCE The major findings of this report are that a highly pathogenic strain of H7N1 avian influenza virus can be adapted to become capable of airborne transmission in mammals without mutations altering receptor specificity. Changes in receptor specificity have been

  8. Novel Reassortant H5N6 Influenza A Virus from the Lao People’s Democratic Republic Is Highly Pathogenic in Chickens

    PubMed Central

    Layton, Daniel S.; Phommachanh, Phouvong; Harper, Jennifer; Payne, Jean; Evans, Ryan M.; Valdeter, Stacey; Walker, Som; Harvey, Gemma; Shan, Songhua; Bruce, Matthew P.; Rootes, Christina L.; Gough, Tamara J.; Rohringer, Andreas; Peck, Grantley R.; Fardy, Sarah J.; Karpala, Adam J.; Johnson, Dayna; Wang, Jianning; Douangngeun, Bounlom; Morrissy, Christopher; Wong, Frank Y. K.; Bean, Andrew G. D.; Bingham, John; Williams, David T.

    2016-01-01

    Avian influenza viruses of H5 subtype can cause highly pathogenic disease in poultry. In March 2014, a new reassortant H5N6 subtype highly pathogenic avian influenza virus emerged in Lao People’s Democratic Republic. We have assessed the pathogenicity, pathobiology and immunological responses associated with this virus in chickens. Infection caused moderate to advanced disease in 6 of 6 chickens within 48 h of mucosal inoculation. High virus titers were observed in blood and tissues (kidney, spleen, liver, duodenum, heart, brain and lung) taken at euthanasia. Viral antigen was detected in endothelium, neurons, myocardium, lymphoid tissues and other cell types. Pro-inflammatory cytokines were elevated compared to non-infected birds. Our study confirmed that this new H5N6 reassortant is highly pathogenic, causing disease in chickens similar to that of Asian H5N1 viruses, and demonstrated the ability of such clade 2.3.4-origin H5 viruses to reassort with non-N1 subtype viruses while maintaining a fit and infectious phenotype. Recent detection of influenza H5N6 poultry infections in Lao PDR, China and Viet Nam, as well as six fatal human infections in China, demonstrate that these emergent highly pathogenic H5N6 viruses may be widely established in several countries and represent an emerging threat to poultry and human populations. PMID:27631618

  9. Isolation, Identification, and Sequencing of a Goose-Derived Newcastle Disease Virus and Determination of Its Pathogenicity.

    PubMed

    Chen, Xiao-Qing; Li, Zi-Bing; Hu, Gui-Xue; Gu, Song-Zhi; Zhang, Shuang; Ying, Ying; Gao, Feng-Shan

    2015-06-01

    In August 2010, geese in the Meihekou area of Jilin province in China were found to be infected by a pathogen that caused a disease similar to Newcastle disease. To determine the causative agent of the infections, a virus was isolated from liver tissues of infected geese, followed by a pathogenicity determination. The isolated virus was named NDV/White Goose/China/Jilin(Meihekou)/MHK-1/2010. Specific primers were designed to amplify the whole genome of the MHK-1 virus, followed by sequencing and splicing of the entire genome. Sequencing and phylogenetic analysis of MHK-1 showed that the isolate was a virulent strain of Newcastle disease virus. The MHK-1 genome is 15,192 nucleotides long, and it belongs to the class II branch of Newcastle disease viruses, as evidenced by the amino acid sequence (112R-R-Q-K-R-F117) of the F protein. The hemagglutinin titer was 1:128 to 1:512. The chicken embryo mean death time, the intracerebral pathogenicity index, and the median lethal dose of chicken embryos of MHK-1 were 43 hr, 1.63, and 10(9)/ml, respectively, which revealed that the newly isolated MHK-1 strain is strongly pathogenic to geese. PMID:26473673

  10. Molecular Biology and Infection of Hepatitis E Virus.

    PubMed

    Nan, Yuchen; Zhang, Yan-Jin

    2016-01-01

    Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus.

  11. Molecular Biology and Infection of Hepatitis E Virus.

    PubMed

    Nan, Yuchen; Zhang, Yan-Jin

    2016-01-01

    Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus. PMID:27656178

  12. Molecular Biology and Infection of Hepatitis E Virus

    PubMed Central

    Nan, Yuchen; Zhang, Yan-Jin

    2016-01-01

    Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus.

  13. Molecular Biology and Infection of Hepatitis E Virus

    PubMed Central

    Nan, Yuchen; Zhang, Yan-Jin

    2016-01-01

    Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus. PMID:27656178

  14. Pathogenicity, Transmission and Antigenic Variation of H5N1 Highly Pathogenic Avian Influenza Viruses

    PubMed Central

    Jiao, Peirong; Song, Hui; Liu, Xiaoke; Song, Yafen; Cui, Jin; Wu, Siyu; Ye, Jiaqi; Qu, Nanan; Zhang, Tiemin; Liao, Ming

    2016-01-01

    H5N1 highly pathogenic avian influenza (HPAI) was one of the most important avian diseases in poultry production of China, especially in Guangdong province. In recent years, new H5N1 highly pathogenic avian influenza viruses (HPAIV) still emerged constantly, although all poultry in China were immunized with H5N1 vaccinations compulsorily. To better understand the pathogenicity and transmission of dominant clades of the H5N1 HPAIVs in chicken from Guangdong in 2012, we chose a clade 7.2 avian influenza virus named A/Chicken/China/G2/2012(H5N1) (G2) and a clade 2.3.2.1 avian influenza virus named A/Duck/China/G3/2012(H5N1) (G3) in our study. Our results showed that the chickens inoculated with 103 EID50 of G2 or G3 viruses all died, and the titers of virus replication detected in several visceral organs were high but different. In the naive contact groups, virus shedding was not detected in G2 group and all chickens survived, but virus shedding was detected in G3 group and all chickens died. These results showed that the two clades of H5N1 HPAIVs had high pathogenicity in chickens and the contact transmission of them was different in chickens. The results of cross reactive HI assay showed that antigens of G2 and G3 were very different from those of current commercial vaccines isolates (Re-4, Re-6, and D7). And to evaluate the protective efficacy of three vaccines against most isolates form Guangdong belonging to clade 2.3.2.1 in 2012, G3 was chosen to challenge the three vaccines such as Re-4, Re-6, and D7. First, chickens were immunized with 0.3 ml Re-4, Re-6, and D7 inactivated vaccines by intramuscular injection, respectively, and then challenged with 106 EID50 of G3 on day 28 post-vaccination. The D7 vaccine had 100% protection against G3 for chickens, the Re-6 vaccine had 88.9%, and the Re-4 vaccine only had 66.7%. Our results suggested that the D7 vaccine could prevent and control H5N1 virus outbreaks more effectively in Guangdong. From the above, it was

  15. Emerging viral pathogens in long-term expatriates (II): Dengue virus.

    PubMed

    Jänisch, T; Preiser, W; Berger, A; Niedrig, M; Mikulicz, U; Thoma, B; Doerr, H W

    1997-10-01

    Dengue virus infections have been well known for many years; still dengue virus is regarded as an 'emerging' pathogen, as the disease profile is changing. Its geographical range and overall incidence, and the incidence of the associated complications, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), are on the increase. Modern-day travel and increasing urbanization seem to be the main contributing factors. In order to estimate the risk of infection during long-term stays in dengue-endemic countries, we tested sera obtained from 323 development aid workers and their family members who had spent on average 9.8 years in dengue-endemic regions for the presence of dengue virus antibodies. Dengue virus antibody screening was done by a commercially available immunofluorescence test (IF). Reactive samples were re-tested by an in-house IF and also tested for cross-reactivity to yellow fever virus using yellow fever IF and neutralization test (NT). Evaluation of the results revealed that the screening test has a specificity of at least 63.2%. In 12 of 19 initially positive cases crossreacting antibodies against yellow fever virus could be ruled out. Three cases remained indeterminable, whereas four of the reactive and 10 (out of 12) of the borderline reactive cases showed crossreactivity with yellow fever virus, probably due to previous vaccination. We found seroprevalence rates of 4.3% with no significant differences related to gender or area of upbringing. Seroprevalence rates were evaluated according to region of suspected or confirmed infection. In two cases the dengue infection had taken a classical clinical course; in another three cases an extraordinary febrile illness was reported in the history. None of the other seropositive individuals had a history of an illness possibly attributable to dengue virus infection. Our results show that there definitely is a risk for long-term expatriates to acquire (mostly non- or oligo-symptomatic) dengue infection

  16. Differential host response, rather than early viral replication efficiency, correlates with pathogenicity caused by influenza viruses.

    PubMed

    Askovich, Peter S; Sanders, Catherine J; Rosenberger, Carrie M; Diercks, Alan H; Dash, Pradyot; Navarro, Garnet; Vogel, Peter; Doherty, Peter C; Thomas, Paul G; Aderem, Alan

    2013-01-01

    Influenza viruses exhibit large, strain-dependent differences in pathogenicity in mammalian hosts. Although the characteristics of severe disease, including uncontrolled viral replication, infection of the lower airway, and highly inflammatory cytokine responses have been extensively documented, the specific virulence mechanisms that distinguish highly pathogenic strains remain elusive. In this study, we focused on the early events in influenza infection, measuring the growth rate of three strains of varying pathogenicity in the mouse airway epithelium and simultaneously examining the global host transcriptional response over the first 24 hours. Although all strains replicated equally rapidly over the first viral life-cycle, their growth rates in both lung and tracheal tissue strongly diverged at later times, resulting in nearly 10-fold differences in viral load by 24 hours following infection. We identified separate networks of genes in both the lung and tracheal tissues whose rapid up-regulation at early time points by specific strains correlated with a reduced viral replication rate of those strains. The set of early-induced genes in the lung that led to viral growth restriction is enriched for both NF-κB binding site motifs and members of the TREM1 and IL-17 signaling pathways, suggesting that rapid, NF-κB -mediated activation of these pathways may contribute to control of viral replication. Because influenza infection extending into the lung generally results in severe disease, early activation of these pathways may be one factor distinguishing high- and low-pathogenicity strains.

  17. Isolation of highly pathogenic avian influenza H5N1 virus from Saker falcons (Falco cherrug) in the Middle East.

    PubMed

    Marjuki, Henju; Wernery, Ulrich; Yen, Hui-Ling; Franks, John; Seiler, Patrick; Walker, David; Krauss, Scott; Webster, Robert G

    2009-01-01

    There is accumulating evidence that birds of prey are susceptible to fatal infection with highly pathogenic avian influenza (HPAI) virus. We studied the antigenic, molecular, phylogenetic, and pathogenic properties of 2 HPAI H5N1 viruses isolated from dead falcons in Saudi Arabia and Kuwait in 2005 and 2007, respectively. Phylogenetic and antigenic analyses grouped both isolates in clade 2.2 (Qinghai-like viruses). However, the viruses appeared to have spread westward via different flyways. It remains unknown how these viruses spread so rapidly from Qinghai after the 2005 outbreak and how they were introduced into falcons in these two countries. The H5N1 outbreaks in the Middle East are believed by some to be mediated by wild migratory birds. However, sporting falcons may be at additional risk from the illegal import of live quail to feed them.

  18. Virus community dynamics in the conifer pathogenic fungus Heterobasidion parviporum following an artificial introduction of a partitivirus.

    PubMed

    Vainio, Eeva J; Piri, Tuula; Hantula, Jarkko

    2013-01-01

    Viruses infecting the conifer pathogenic fungus Heterobasidion annosum sensu lato are intracellular and spread via anastomosis contacts. In the laboratory, these viruses transmit readily even between somatically incompatible isolates, but their dispersal capacity in natural conditions has not been previously studied. We introduced a mycovirus to a heavily diseased forest site by inoculating Norway spruce stumps with heartrot decay using a mycelial suspension of Heterobasidion parviporum strain RT3.49C hosting the partitivirus strain HetRV4-pa1. The Heterobasidion population at the sample plot was screened for mycoviruses prior to and after the inoculation. Based on sequence analysis, the resident H. parviporum strains harbored six different strains of the virus species Heterobasidion RNA virus 6 (HetRV6) and one strain of HetRV4 prior to the inoculation. After three growth seasons, the inoculated H. parviporum host strain was not detected, but the introduced virus had infected two resident H. parviporum genets. The presence of a preexisting HetRV6 infection did not hinder spread of the introduced partitivirus but resulted in coinfections instead. The resident HetRV6 virus population seemed to be highly stable during the incubation period, while the single indigenous HetRV4 infection was not detected after the inoculation. In laboratory infection experiments, the introduced virus could be transmitted successfully into all of the resident H. parviporum genets. This study shows for the first time transmission of a Heterobasidion virus between somatically incompatible hosts in natural conditions.

  19. Phylogenetic analysis and pathogenicity of H3 subtype avian influenza viruses isolated from live poultry markets in China.

    PubMed

    Cui, Hongrui; Shi, Ying; Ruan, Tao; Li, Xuesong; Teng, Qiaoyang; Chen, Hongjun; Yang, Jianmei; Liu, Qinfang; Li, Zejun

    2016-01-01

    H3 subtype influenza A virus is one of the main subtypes that threats both public and animal health. However, the evolution and pathogenicity of H3 avian influenza virus (AIV) circulating in domestic birds in China remain largely unclear. In this study, seven H3 AIVs (four H3N2 and three H3N8) were isolated from poultry in live poultry market (LPM) in China. Phylogenetic analyses of full genomes showed that all viruses were clustered into Eurasian lineage, except N8 genes of two H3N8 isolates fell into North American lineage. Intriguingly, the N8 gene of one H3N8 and PB2, PB1, NP and NS of two H3N2 isolates have close relationship with those of the highly pathogenic H5N8 viruses circulating in Korea and United States, suggesting that the H3-like AIV may contribute internal genes to the highly pathogenic H5N8 viruses. Phylogenetic tree of HA gene and antigenic cross-reactivity results indicated that two antigenically different H3 viruses are circulating in LPM in China. Most of the H3 viruses replicated in mice lung and nasal turbinate without prior adaptation, and the representative H3 viruses infected chickens without causing clinical signs. The reassortment of H3 subtype influenza viruses warrants continuous surveillance in LPM in China. PMID:27270298

  20. Rabies virus glycoprotein is an important determinant for the induction of innate immune responses and the pathogenic mechanisms.

    PubMed

    Zhang, Guoqing; Wang, Hualei; Mahmood, Fazal; Fu, Zhen F

    2013-03-23

    Our previous studies have suggested that street and fixed rabies viruses (RABVs) induce diseases in the mouse model via different mechanisms. In the present study, attempts were made to determine if it is the glycoprotein (G) that is responsible for the observed differences in the pathogenic mechanisms. To this end, an infectious clone from fixed virus B2c was established and used as a backbone for exchange of the G from street viruses. The rate of viral replication, expression of viral proteins, and the induction of innate immune responses were compared in cells or in mice infected with each of the viruses. Furthermore, the infiltration of inflammatory cells into the CNS and the enhancement of blood-brain barrier (BBB) permeability were also compared. It was found that fixed viruses induced stronger innate immune responses (expression of chemokines, infiltration of inflammatory cells, and enhancement of BBB permeability) than street RABV or recombinant viruses expressing the G from street RABVs. Fixed viruses induce disease via an immune-mediated pathogenic mechanism while street viruses or recombinant viruses expressing the G from street RABVs induce diseases via a mechanism other than immune-mediated pathogenesis. Therefore, RABV G is an important determinant for the induction of innate immune responses and consequently the pathogenic mechanisms.

  1. Phylogenetic analysis and pathogenicity of H3 subtype avian influenza viruses isolated from live poultry markets in China

    PubMed Central

    Cui, Hongrui; Shi, Ying; Ruan, Tao; Li, Xuesong; Teng, Qiaoyang; Chen, Hongjun; Yang, Jianmei; Liu, Qinfang; Li, Zejun

    2016-01-01

    H3 subtype influenza A virus is one of the main subtypes that threats both public and animal health. However, the evolution and pathogenicity of H3 avian influenza virus (AIV) circulating in domestic birds in China remain largely unclear. In this study, seven H3 AIVs (four H3N2 and three H3N8) were isolated from poultry in live poultry market (LPM) in China. Phylogenetic analyses of full genomes showed that all viruses were clustered into Eurasian lineage, except N8 genes of two H3N8 isolates fell into North American lineage. Intriguingly, the N8 gene of one H3N8 and PB2, PB1, NP and NS of two H3N2 isolates have close relationship with those of the highly pathogenic H5N8 viruses circulating in Korea and United States, suggesting that the H3-like AIV may contribute internal genes to the highly pathogenic H5N8 viruses. Phylogenetic tree of HA gene and antigenic cross-reactivity results indicated that two antigenically different H3 viruses are circulating in LPM in China. Most of the H3 viruses replicated in mice lung and nasal turbinate without prior adaptation, and the representative H3 viruses infected chickens without causing clinical signs. The reassortment of H3 subtype influenza viruses warrants continuous surveillance in LPM in China. PMID:27270298

  2. Mechanisms of transmission and spread of H5N1 high pathogenicity avian influenza virus in birds and mammals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Eurasian-African H5N1 high pathogenicity avian influenza (HPAI) virus has crossed multiple species barriers to infect poultry, captive and wild birds, carnivorous mammals and humans. The specific transmission mechanisms are unclear in most cases, but experimental studies and field data sug...

  3. Surveillance for highly pathogenic avian influenza virus in wild birds during outbreaks in domestic poultry, Minnesota, 2015

    USGS Publications Warehouse

    Jennelle, Christopher S.; Carstensen, Michelle; Hildebrand, Erik C.; Cornicelli, Louis; Wolf, Paul C.; Grear, Daniel; Ip, Hon S.; VanDalen, Kaci K.; Minicucci, Larissa A.

    2016-01-01

    In 2015, a major outbreak of highly pathogenic avian influenza virus (HPAIV) infection devastated poultry facilities in Minnesota, USA. To clarify the role of wild birds, we tested 3,139 waterfowl fecal samples and 104 sick and dead birds during March 9–June 4, 2015. HPAIV was isolated from a Cooper’s hawk but not from waterfowl.

  4. Combinatorially selected defense peptides protect plant roots from pathogen infection

    PubMed Central

    Fang, Zhiwei David; Laskey, James G.; Huang, Shaoxing; Bilyeu, Kristin D.; Morris, Roy O.; Schmidt, Francis J.; English, James T.

    2006-01-01

    Agricultural productivity and sustainability are continually challenged by emerging and indigenous pathogens. Currently, many pathogens can be combated only with biocides or environmentally dangerous fumigants. Here, we report a rapid and pathogen-specific strategy to reduce infection by organisms that target plant roots. Combinatorially selected defense peptides, previously shown to effect premature encystment of Phytophthora capsici zoospores, were fused to maize cytokinin oxidase/dehydrogenase as a display scaffold. When expressed in tomato roots, the peptide-scaffold constructs were secreted and accumulated to sufficient concentrations in the rhizosphere to induce zoospore encystment and thereby deter taxis to the root surface. Pathogen infection was significantly inhibited in roots expressing bioactive peptides fused to the maize cytokinin oxidase/dehydrogenase scaffold. This peptide-delivery technology is broadly applicable for rapid development of plant defense attributes against plant pathogens. PMID:17030803

  5. Proteomic analysis of host responses in HepG2 cells during dengue virus infection.

    PubMed

    Pattanakitsakul, Sa-Nga; Rungrojcharoenkit, Kamonthip; Kanlaya, Rattiyaporn; Sinchaikul, Supachok; Noisakran, Sansanee; Chen, Shui-Tein; Malasit, Prida; Thongboonkerd, Visith

    2007-12-01

    Dengue virus infection remains a public health problem worldwide. However, its pathogenic mechanisms and pathophysiology are still poorly understood. We performed proteomic analysis to evaluate early host responses (as indicated by altered proteins) in human target cells during dengue virus infection. HepG2 cells were infected with dengue virus serotype 2 (DEN-2) at multiplicity of infection (MOI) of 0.1, 0.5, and 1.0. Quantitative analyses of DEN-2 infection and cell death at 12, 24, and 48 h postinfection showed that the MOI of 1.0 with 24 h postinfection duration was the optimal condition to evaluate early host responses, as this condition provided the high %Infection ( approximately 80%), while %Cell death ( approximately 20%) was comparable to that of the mock-control cells. Proteins derived from the mock-control and DEN-2-infected cells were resolved by 2-D PAGE ( n = 5 gels for each group) and visualized by SYPRO Ruby stain. Quantitative intensity analysis revealed 17 differentially expressed proteins, which were successfully identified by peptide mass fingerprinting. Most of these altered proteins were the key factors involved in transcription and translation processes. Further functional study on these altered proteins may lead to better understanding of the pathogenic mechanisms and host responses to dengue virus infection, and also to the identification of new therapeutic targets for dengue virus infection.

  6. Immune Responses and Lassa Virus Infection

    PubMed Central

    Russier, Marion; Pannetier, Delphine; Baize, Sylvain

    2012-01-01

    Lassa fever is a hemorrhagic fever endemic to West Africa and caused by Lassa virus, an Old World arenavirus. It may be fatal, but most patients recover from acute disease and some experience asymptomatic infection. The immune mechanisms associated with these different outcomes have not yet been fully elucidated, but considerable progress has recently been made, through the use of in vitro human models and nonhuman primates, the only relevant animal model that mimics the pathophysiology and immune responses induced in patients. We discuss here the roles of the various components of the innate and adaptive immune systems in Lassa virus infection and in the control of viral replication and pathogenesis. PMID:23202504

  7. Control of viruses infecting grapevine.

    PubMed

    Maliogka, Varvara I; Martelli, Giovanni P; Fuchs, Marc; Katis, Nikolaos I

    2015-01-01

    Grapevine is a high value vegetatively propagated fruit crop that suffers from numerous viruses, including some that seriously affect the profitability of vineyards. Nowadays, 64 viruses belonging to different genera and families have been reported in grapevines and new virus species will likely be described in the future. Three viral diseases namely leafroll, rugose wood, and infectious degeneration are of major economic importance worldwide. The viruses associated with these diseases are transmitted by mealybugs, scale and soft scale insects, or dagger nematodes. Here, we review control measures of the major grapevine viral diseases. More specifically, emphasis is laid on (i) approaches for the production of clean stocks and propagative material through effective sanitation, robust diagnosis, as well as local and regional certification efforts, (ii) the management of vectors of viruses using cultural, biological, and chemical methods, and (iii) the production of resistant grapevines mainly through the application of genetic engineering. The benefits and limitations of the different control measures are discussed with regard to accomplishments and future research directions.

  8. Pathobiological Characterization of a Novel Reassortant Highly Pathogenic H5N1 Virus Isolated in British Columbia, Canada, 2015

    PubMed Central

    Berhane, Yohannes; Kobasa, Darwyn; Embury-Hyatt, Carissa; Pickering, Brad; Babiuk, Shawn; Joseph, Tomy; Bowes, Victoria; Suderman, Mathew; Leung, Anders; Cottam-Birt, Colleen; Hisanaga, Tamiko; Pasick, John

    2016-01-01

    In the current study, we describe the pathobiologic characteristics of a novel reassortant virus - A/chicken/BC/FAV-002/2015 (H5N1) belonging to clade 2.3.4.4 that was isolated from backyard chickens in British Columbia, Canada. Sequence analyses demonstrate PB1, PA, NA and NS gene segments were of North American lineage while PB2, HA, NP and M were derived from a Eurasian lineage H5N8 virus. This novel virus had a 19 amino acid deletion in the neuraminidase stalk. We evaluated the pathogenic potential of this isolate in various animal models. The virus was highly pathogenic to mice with a LD50 of 10 plaque forming units (PFU), but had limited tissue tropism. It caused only subclinical infection in pigs which did result in seroconversion. This virus was highly pathogenic to chickens, turkeys, juvenile Muscovy ducks (Cairnia moschata foma domestica) and adult Chinese geese (Anser cynoides domesticus) causing a systemic infection in all species. The virus was also efficiently transmitted and resulted in mortality in naïve contact ducks, geese and chickens. Our findings indicate that this novel H5N1 virus has a wide host range and enhanced surveillance of migratory waterfowl may be necessary in order to determine its potential to establish itself in the wild bird reservoir. PMID:26988892

  9. Pathobiological Characterization of a Novel Reassortant Highly Pathogenic H5N1 Virus Isolated in British Columbia, Canada, 2015.

    PubMed

    Berhane, Yohannes; Kobasa, Darwyn; Embury-Hyatt, Carissa; Pickering, Brad; Babiuk, Shawn; Joseph, Tomy; Bowes, Victoria; Suderman, Mathew; Leung, Anders; Cottam-Birt, Colleen; Hisanaga, Tamiko; Pasick, John

    2016-01-01

    In the current study, we describe the pathobiologic characteristics of a novel reassortant virus - A/chicken/BC/FAV-002/2015 (H5N1) belonging to clade 2.3.4.4 that was isolated from backyard chickens in British Columbia, Canada. Sequence analyses demonstrate PB1, PA, NA and NS gene segments were of North American lineage while PB2, HA, NP and M were derived from a Eurasian lineage H5N8 virus. This novel virus had a 19 amino acid deletion in the neuraminidase stalk. We evaluated the pathogenic potential of this isolate in various animal models. The virus was highly pathogenic to mice with a LD50 of 10 plaque forming units (PFU), but had limited tissue tropism. It caused only subclinical infection in pigs which did result in seroconversion. This virus was highly pathogenic to chickens, turkeys, juvenile Muscovy ducks (Cairnia moschata foma domestica) and adult Chinese geese (Anser cynoides domesticus) causing a systemic infection in all species. The virus was also efficiently transmitted and resulted in mortality in naïve contact ducks, geese and chickens. Our findings indicate that this novel H5N1 virus has a wide host range and enhanced surveillance of migratory waterfowl may be necessary in order to determine its potential to establish itself in the wild bird reservoir. PMID:26988892

  10. Pathobiological Characterization of a Novel Reassortant Highly Pathogenic H5N1 Virus Isolated in British Columbia, Canada, 2015.

    PubMed

    Berhane, Yohannes; Kobasa, Darwyn; Embury-Hyatt, Carissa; Pickering, Brad; Babiuk, Shawn; Joseph, Tomy; Bowes, Victoria; Suderman, Mathew; Leung, Anders; Cottam-Birt, Colleen; Hisanaga, Tamiko; Pasick, John

    2016-03-18

    In the current study, we describe the pathobiologic characteristics of a novel reassortant virus - A/chicken/BC/FAV-002/2015 (H5N1) belonging to clade 2.3.4.4 that was isolated from backyard chickens in British Columbia, Canada. Sequence analyses demonstrate PB1, PA, NA and NS gene segments were of North American lineage while PB2, HA, NP and M were derived from a Eurasian lineage H5N8 virus. This novel virus had a 19 amino acid deletion in the neuraminidase stalk. We evaluated the pathogenic potential of this isolate in various animal models. The virus was highly pathogenic to mice with a LD50 of 10 plaque forming units (PFU), but had limited tissue tropism. It caused only subclinical infection in pigs which did result in seroconversion. This virus was highly pathogenic to chickens, turkeys, juvenile Muscovy ducks (Cairnia moschata foma domestica) and adult Chinese geese (Anser cynoides domesticus) causing a systemic infection in all species. The virus was also efficiently transmitted and resulted in mortality in naïve contact ducks, geese and chickens. Our findings indicate that this novel H5N1 virus has a wide host range and enhanced surveillance of migratory waterfowl may be necessary in order to determine its potential to establish itself in the wild bird reservoir.

  11. Characterization of Lethal Zika Virus Infection in AG129 Mice

    PubMed Central

    Walker, Emma C.; Larkin, Katrina E.; Camacho, Erwin; Osorio, Jorge E.

    2016-01-01

    Background Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever, which often is accompanied by maculopapular rash, headache, and myalgia. During the current outbreak in South America, ZIKV infection during pregnancy has been hypothesized to cause microcephaly and other diseases. The detection of ZIKV in fetal brain tissue supports this hypothesis. Because human infections with ZIKV historically have remained sporadic and, until recently, have been limited to small-scale epidemics, neither the disease caused by ZIKV nor the molecular determinants of virulence and/or pathogenicity have been well characterized. Here, we describe a small animal model for wild-type ZIKV of the Asian lineage. Methodology/Principal Findings Using mice deficient in interferon α/β and Ɣ receptors (AG129 mice), we report that these animals were highly susceptible to ZIKV infection and disease, succumbing within seven to eight days. Rapid viremic dissemination was observed in visceral organs and brain; but only was associated with severe pathologies in the brain and muscle. Finally, these results were consistent across challenge routes, age of mice, and inoculum doses. These data represent a mouse model for ZIKV that is not dependent on adapting ZIKV to intracerebral passage in mice. Conclusions/Significance Foot pad injection of AG129 mice with ZIKV represents a biologically relevant model for studying ZIKV infection and disease development following wild-type virus inoculation without the requirement for adaptation of the virus or intracerebral delivery of the virus. This newly developed Zika disease model can be exploited to identify determinants of ZIKV virulence and reveal molecular mechanisms that control the virus-host interaction, providing a framework for rational design of acute phase therapeutics and for vaccine efficacy testing. PMID:27093158

  12. Genome Wide Host Gene Expression Analysis in Chicken Lungs Infected with Avian Influenza Viruses

    PubMed Central

    Gandhale, Pradeep N.; Kumar, Himanshu; Kulkarni, Diwakar D.

    2016-01-01

    The molecular pathogenesis of avian influenza infection varies greatly with individual bird species and virus strain. The molecular pathogenesis of the highly pathogenic avian influenza virus (HPAIV) or the low pathogenic avian influenza virus (LPAIV) infection in avian species remains poorly understood. Thus, global immune response of chickens infected with HPAI H5N1 (A/duck/India/02CA10/2011) and LPAI H9N2 (A/duck/India/249800/2010) viruses was studied using microarray to identify crucial host genetic components responsive to these infection. HPAI H5N1 virus induced excessive expression of type I IFNs (IFNA and IFNG), cytokines (IL1B, IL18, IL22, IL13, and IL12B), chemokines (CCL4, CCL19, CCL10, and CX3CL1) and IFN stimulated genes (OASL, MX1, RSAD2, IFITM5, IFIT5, GBP 1, and EIF2AK) in lung tissues. This dysregulation of host innate immune genes may be the critical determinant of the severity and the outcome of the influenza infection in chickens. In contrast, the expression levels of most of these genes was not induced in the lungs of LPAI H9N2 virus infected chickens. This study indicated the relationship between host immune genes and their roles in pathogenesis of HPAIV infection in chickens. PMID:27071061

  13. Tissue tropism of highly pathogenic avian influenza virus subtype H5N1 in naturally infected mute swans (Cygnus Olor ), domestic geese (Aser Anser var. domestica), pekin ducks (Anas platyrhynchos) and mulard ducks ( Cairina moschata x anas platyrhynchos).

    PubMed

    Szeredi, Levente; Dán, Adám; Pálmai, Nimród; Ursu, Krisztina; Bálint, Adám; Szeleczky, Zsófia; Ivanics, Eva; Erdélyi, Károly; Rigó, Dóra; Tekes, Lajos; Glávits, Róbert

    2010-03-01

    The 2006 epidemic due to highly pathogenic avian influenza virus (HPAIV) subtype H5N1 in Hungary caused the most severe losses in waterfowl which were, according to the literature at the time, supposed to be the most resistant to this pathogen. The presence of pathological lesions and the amount of viral antigen were quantified by gross pathology, histopathology and immunohistochemistry (IHC) in the organs of four waterfowl species [mute swans (n = 10), domestic geese (n = 6), mulard ducks (n = 6) and Pekin ducks (n = 5)] collected during the epidemic. H5N1 subtype HPAIV was isolated from all birds examined. Quantitative real-time reverse transcriptase-polymerase chain reaction (qRRT-PCR) was also applied on a subset of samples [domestic geese (n = 3), mulard (n = 4) and Pekin duck (n = 4)] in order to compare its sensitivity with IHC. Viral antigen was detected by IHC in all cases. However, the overall presence of viral antigen in tissue samples was quite variable: virus antigen was present in 56/81 (69%) swan, 22/38 (58%) goose, 28/46 (61%) mulard duck and 5/43 (12%) Pekin duck tissue samples. HPAIV subtype H5N1 was detected by qRRT-PCR in all birds examined, in 19/19 (100%) goose, 7/28 (25%) mulard duck and 12/28 (43%) Pekin duck tissue samples. As compared to qRRTPCR, the IHC was less sensitive in geese and Pekin ducks but more sensitive in mulard ducks. The IHC was consistently positive above 4.31 log10 copies/reaction but it gave very variable results below that level. Neurotropism of the isolated virus strains was demonstrated by finding the largest amount of viral antigen and the highest average RNA load in the brain in all four waterfowl species examined.

  14. Widespread detection of highly pathogenic H5 influenza viruses in wild birds from the Pacific Flyway of the United States.

    PubMed

    Bevins, S N; Dusek, R J; White, C L; Gidlewski, T; Bodenstein, B; Mansfield, K G; DeBruyn, P; Kraege, D; Rowan, E; Gillin, C; Thomas, B; Chandler, S; Baroch, J; Schmit, B; Grady, M J; Miller, R S; Drew, M L; Stopak, S; Zscheile, B; Bennett, J; Sengl, J; Brady, Caroline; Ip, H S; Spackman, E; Killian, M L; Torchetti, M K; Sleeman, J M; Deliberto, T J

    2016-01-01

    A novel highly pathogenic avian influenza virus belonging to the H5 clade 2.3.4.4 variant viruses was detected in North America in late 2014. Motivated by the identification of these viruses in domestic poultry in Canada, an intensive study was initiated to conduct highly pathogenic avian influenza surveillance in wild birds in the Pacific Flyway of the United States. A total of 4,729 hunter-harvested wild birds were sampled and highly pathogenic avian influenza virus was detected in 1.3% (n = 63). Three H5 clade 2.3.4.4 subtypes were isolated from wild birds, H5N2, H5N8, and H5N1, representing the wholly Eurasian lineage H5N8 and two novel reassortant viruses. Testing of 150 additional wild birds during avian morbidity and mortality investigations in Washington yielded 10 (6.7%) additional highly pathogenic avian influenza isolates (H5N8 = 3 and H5N2 = 7). The geographically widespread detection of these viruses in apparently healthy wild waterfowl suggest that the H5 clade 2.3.4.4 variant viruses may behave similarly in this taxonomic group whereby many waterfowl species are susceptible to infection but do not demonstrate obvious clinical disease. Despite these findings in wild waterfowl, mortality has been documented for some wild bird species and losses in US domestic poultry during the first half of 2015 were unprecedented. PMID:27381241

  15. Widespread detection of highly pathogenic H5 influenza viruses in wild birds from the Pacific Flyway of the United States

    USGS Publications Warehouse

    Bevins, S.N.; Dusek, Robert J.; White, C. LeAnn; Gidlewski, Thomas; Bodenstein, B.; Mansfield, Kristin G.; DeBruyn, Paul; Kraege, Donald K.; Rowan, E.L.; Gillin, Colin; Thomas, B.; Chandler, S.; Baroch, J.; Schmit, B.; Grady, M. J.; Miller, R. S.; Drew, M.L.; Stopak, S.; Zscheile, B.; Bennett, J.; Sengl, J.; Brady, Caroline; Ip, Hon S.; Spackman, Erica; Killian, M. L.; Torchetti, Mia Kim; Sleeman, Jonathan M.; DeLiberto, T.J.

    2016-01-01

    A novel highly pathogenic avian influenza virus belonging to the H5 clade 2.3.4.4 variant viruses was detected in North America in late 2014. Motivated by the identification of these viruses in domestic poultry in Canada, an intensive study was initiated to conduct highly pathogenic avian influenza surveillance in wild birds in the Pacific Flyway of the United States. A total of 4,729 hunter-harvested wild birds were sampled and highly pathogenic avian influenza virus was detected in 1.3% (n = 63). Three H5 clade 2.3.4.4 subtypes were isolated from wild birds, H5N2, H5N8, and H5N1, representing the wholly Eurasian lineage H5N8 and two novel reassortant viruses. Testing of 150 additional wild birds during avian morbidity and mortality investigations in Washington yielded 10 (6.7%) additional highly pathogenic avian influenza isolates (H5N8 = 3 and H5N2 = 7). The geographically widespread detection of these viruses in apparently healthy wild waterfowl suggest that the H5 clade 2.3.4.4 variant viruses may behave similarly in this taxonomic group whereby many waterfowl species are susceptible to infection but do not demonstrate obvious clinical disease. Despite these findings in wild waterfowl, mortality has been documented for some wild bird species and losses in US domestic poultry during the first half of 2015 were unprecedented.

  16. Widespread detection of highly pathogenic H5 influenza viruses in wild birds from the Pacific Flyway of the United States

    PubMed Central

    Bevins, S. N.; Dusek, R. J.; White, C. L.; Gidlewski, T.; Bodenstein, B.; Mansfield, K. G.; DeBruyn, P.; Kraege, D.; Rowan, E.; Gillin, C.; Thomas, B.; Chandler, S.; Baroch, J.; Schmit, B.; Grady, M. J.; Miller, R. S.; Drew, M. L.; Stopak, S.; Zscheile, B.; Bennett, J.; Sengl, J.; Brady, Caroline; Ip, H. S.; Spackman, E.; Killian, M. L.; Torchetti, M. K.; Sleeman, J. M.; Deliberto, T. J.

    2016-01-01

    A novel highly pathogenic avian influenza virus belonging to the H5 clade 2.3.4.4 variant viruses was detected in North America in late 2014. Motivated by the identification of these viruses in domestic poultry in Canada, an intensive study was initiated to conduct highly pathogenic avian influenza surveillance in wild birds in the Pacific Flyway of the United States. A total of 4,729 hunter-harvested wild birds were sampled and highly pathogenic avian influenza virus was detected in 1.3% (n = 63). Three H5 clade 2.3.4.4 subtypes were isolated from wild birds, H5N2, H5N8, and H5N1, representing the wholly Eurasian lineage H5N8 and two novel reassortant viruses. Testing of 150 additional wild birds during avian morbidity and mortality investigations in Washington yielded 10 (6.7%) additional highly pathogenic avian influenza isolates (H5N8 = 3 and H5N2 = 7). The geographically widespread detection of these viruses in apparently healthy wild waterfowl suggest that the H5 clade 2.3.4.4 variant viruses may behave similarly in this taxonomic group whereby many waterfowl species are susceptible to infection but do not demonstrate obvious clinical disease. Despite these findings in wild waterfowl, mortality has been documented for some wild bird species and losses in US domestic poultry during the first half of 2015 were unprecedented. PMID:27381241

  17. Identification of Plum pox virus pathogenicity determinants in herbaceous and woody hosts.

    PubMed

    Salvador, B; Delgadillo, M O; Sáenz, P; García, J A; Simón-Mateo, C

    2008-01-01

    Plum pox virus (PPV) is a member of the genus Potyvirus that is able to infect a large variety of plant species, including trees of the genus Prunus, its natural host. When some PPV isolates are propagated for an extended time in herbaceous plants, their ability to infect trees is reduced. The molecular basis of this change in host infectivity is poorly understood. We report the construction of hybrid viruses from cDNA clones of two D-strain isolates of PPV, PPV-D and PPV-R, which differ in their host range. PPV-D can infect GF305 peach seedlings efficiently, however, it is unable to infect Nicotiana clevelandii plants. Conversely, PPV-R infects N. clevelandii, but not GF305 peach seedlings. The analyses of the hybrid viruses showed that, although determinants of PPV pathogenicity are extensively spread throughout the PPV genome, the 3' terminal region of the PPV-R genome, including the 3' noncoding region and the coding regions for the coat protein (CP), NIb, and part of NIa protein, is sufficient to confer infectivity of N. clevelandii in a PPV-D background. Our data demonstrate a high concentration of amino acid substitutions in the CP and a host-specific effect of a deletion at the N terminus of this protein in PPV pathogenicity in peach and N. clevelandii infectivity experiments. These results suggest that relevant host specificity determinants are located in the N-terminal region of the CP. The analyses of the PPV-R and PPV-D chimeras also showed that key host-specific pathogenicity determinants lie in the 5' terminal third of the PPV genome, a region that spans proteins P1, HCPro, and P3. The selection of mutations in only a few specific residues in proteins P1, P3, and 6K1 after partial adaptation of a chimeric virus (BD-GFP) to N. clevelandii further suggests a relevant role for these proteins in host adaptation.

  18. Naturally occurring animal models of human hepatitis E virus infection.

    PubMed

    Yugo, Danielle M; Cossaboom, Caitlin M; Meng, Xiang-Jin

    2014-01-01

    Hepatitis E virus (HEV) is a single-stranded, positive-sense RNA virus in the family Hepeviridae. Hepatitis E caused by HEV is a clinically important global disease. There are currently four well-characterized genotypes of HEV in mammalian species, although numerous novel strains of HEV likely belonging to either new genotypes or species have recently been identified from several other animal species. HEV genotypes 1 and 2 are limited to infection in humans, whereas genotypes 3 and 4 infect an expanding host range of animal species and are zoonotic to humans. Historical animal models include various species of nonhuman primates, which have been indispensable for the discovery of human HEV and for understanding its pathogenesis and course of infection. With the genetic identification and characterization of animal strains of HEV, a number of naturally occurring animal models such as swine, chicken, and rabbit have recently been developed for various aspects of HEV research, including vaccine trials, pathogenicity, cross-species infection, mechanism of virus replication, and molecular biology studies. Unfortunately, the current available animal models for HEV are still inadequate for certain aspects of HEV research. For instance, an animal model is still lacking to study the underlying mechanism of severe and fulminant hepatitis E during pregnancy. Also, an animal model that can mimic chronic HEV infection is critically needed to study the mechanism leading to chronicity in immunocompromised individuals. Genetic identification of additional novel animal strains of HEV may lead to the development of better naturally occurring animal models for HEV. This article reviews the current understanding of animal models of HEV infection in both natural and experimental infection settings and identifies key research needs and limitations.

  19. Heterogeneous and Dynamic Prevalence of Asymptomatic Influenza Virus Infections

    PubMed Central

    Furuya-Kanamori, Luis; Cox, Mitchell; Milinovich, Gabriel J.; Magalhaes, Ricardo J. Soares; Mackay, Ian M.

    2016-01-01

    Influenza infection manifests in a wide spectrum of severity, including symptomless pathogen carriers. We conducted a systematic review and meta-analysis of 55 studies to elucidate the proportional representation of these asymptomatic infected persons. We observed extensive heterogeneity among these studies. The prevalence of asymptomatic carriage (total absence of symptoms) ranged from 5.2% to 35.5% and subclinical cases (illness that did not meet the criteria for acute respiratory or influenza-like illness) from 25.4% to 61.8%. Statistical analysis showed that the heterogeneity could not be explained by the type of influenza, the laboratory tests used to detect the virus, the year of the study, or the location of the study. Projections of infection spread and strategies for disease control require that we identify the proportional representation of these insidious spreaders early on in the emergence of new influenza subtypes or strains and track how this rate evolves over time and space. PMID:27191967

  20. Heterogeneous and Dynamic Prevalence of Asymptomatic Influenza Virus Infections.

    PubMed

    Furuya-Kanamori, Luis; Cox, Mitchell; Milinovich, Gabriel J; Magalhaes, Ricardo J Soares; Mackay, Ian M; Yakob, Laith

    2016-06-01

    Influenza infection manifests in a wide spectrum of severity, including symptomless pathogen carriers. We conducted a systematic review and meta-analysis of 55 studies to elucidate the proportional representation of these asymptomatic infected persons. We observed extensive heterogeneity among these studies. The prevalence of asymptomatic carriage (total absence of symptoms) ranged from 5.2% to 35.5% and subclinical cases (illness that did not meet the criteria for acute respiratory or influenza-like illness) from 25.4% to 61.8%. Statistical analysis showed that the heterogeneity could not be explained by the type of influenza, the laboratory tests used to detect the virus, the year of the study, or the location of the study. Projections of infection spread and strategies for disease control require that we identify the proportional representation of these insidious spreaders early on in the emergence of new influenza subtypes or strains and track how this rate evolves over time and space. PMID:27191967

  1. Interferon Induction by RNA Viruses and Antagonism by Viral Pathogens

    PubMed Central

    Nan, Yuchen; Nan, Guoxin; Zhang, Yan-Jin

    2014-01-01

    Interferons are a group of small proteins that play key roles in host antiviral innate immunity. Their induction mainly relies on host pattern recognition receptors (PRR). Host PRR for RNA viruses include Toll-like receptors (TLR) and retinoic acid-inducible gene I (RIG-I) like receptors (RLR). Activation of both TLR and RLR pathways can eventually lead to the secretion of type I IFNs, which can modulate both innate and adaptive immune responses against viral pathogens. Because of the important roles of interferons, viruses have evolved multiple strategies to evade host TLR and RLR mediated signaling. This review focuses on the mechanisms of interferon induction and antagonism of the antiviral strategy by RNA viruses. PMID:25514371

  2. Infection of Bergmann glia in the cerebellum of a skunk experimentally infected with street rabies virus.

    PubMed

    Jackson, A C; Phelan, C C; Rossiter, J P

    2000-10-01

    Rabies virus is a highly neuronotropic virus and glial cell infection is not prominent in the central nervous system (CNS). Paraffin-embedded tissues from the cerebella of skunks experimentally infected with either a skunk salivary gland isolate of street rabies virus or the challenge virus standard (CVS) strain of fixed rabies virus were examined with immunoperoxidase staining for rabies virus antigen by using an anti-rabies virus nucleocapsid protein monoclonal antibody. A skunk infected with street rabies virus showed prominent infection of Bergmann glia. Although infected Purkinje cells were observed, they usually demonstrated a relatively small amount of antigen in their perikarya. A CVS-infected skunk showed many intensely labeled Purkinje cells and a relatively small number of infected Bergmann glia. These findings indicate that although rabies virus is a highly neuronotropic virus, street rabies virus strains do not always demonstrate strict neuronotropism in the central nervous system.

  3. A Network Integration Approach to Predict Conserved Regulators Related to Pathogenicity of Influenza and SARS-CoV Respiratory Viruses

    PubMed Central

    Mitchell, Hugh D.; Eisfeld, Amie J.; Sims, Amy C.; McDermott, Jason E.; Matzke, Melissa M.; Webb-Robertson, Bobbi-Jo M.; Tilton, Susan C.; Tchitchek, Nicolas; Josset, Laurence; Li, Chengjun; Ellis, Amy L.; Chang, Jean H.; Heegel, Robert A.; Luna, Maria L.; Schepmoes, Athena A.; Shukla, Anil K.; Metz, Thomas O.; Neumann, Gabriele; Benecke, Arndt G.; Smith, Richard D.; Baric, Ralph S.; Kawaoka, Yoshihiro; Katze, Michael G.; Waters, Katrina M.

    2013-01-01

    Respiratory infections stemming from influenza viruses and the Severe Acute Respiratory Syndrome corona virus (SARS-CoV) represent a serious public health threat as emerging pandemics. Despite efforts to identify the critical interactions of these viruses with host machinery, the key regulatory events that lead to disease pathology remain poorly targeted with therapeutics. Here we implement an integrated network interrogation approach, in which proteome and transcriptome datasets from infection of both viruses in human lung epithelial cells are utilized to predict regulatory genes involved in the host response. We take advantage of a novel “crowd-based” approach to identify and combine ranking metrics that isolate genes/proteins likely related to the pathogenicity of SARS-CoV and influenza virus. Subsequently, a multivariate regression model is used to compare predicted lung epithelial regulatory influences with data derived from other respiratory virus infection models. We predicted a small set of regulatory factors with conserved behavior for consideration as important components of viral pathogenesis that might also serve as therapeutic targets for intervention. Our results demonstrate the utility of integrating diverse ‘omic datasets to predict and prioritize regulatory features conserved across multiple pathogen infection models. PMID:23935999

  4. A Network Integration Approach to Predict Conserved Regulators Related to Pathogenicity of Influenza and SARS-CoV Respiratory Viruses

    SciTech Connect

    Mitchell, Hugh D.; Eisfeld, Amie J.; Sims, Amy; McDermott, Jason E.; Matzke, Melissa M.; Webb-Robertson, Bobbie-Jo M.; Tilton, Susan C.; Tchitchek, Nicholas; Josset, Laurence; Li, Chengjun; Ellis, Amy L.; Chang, Jean H.; Heegel, Robert A.; Luna, Maria L.; Schepmoes, Athena A.; Shukla, Anil K.; Metz, Thomas O.; Neumann, Gabriele; Benecke, Arndt; Smith, Richard D.; Baric, Ralph; Kawaoka, Yoshihiro; Katze, Michael G.; Waters, Katrina M.

    2013-07-25

    Respiratory infections stemming from influenza viruses and the Severe Acute Respiratory Syndrome corona virus (SARS-CoV) represent a serious public health threat as emerging pandemics. Despite efforts to identify the critical interactions of these viruses with host machinery, the key regulatory events that lead to disease pathology remain poorly targeted with therapeutics. Here we implement an integrated network interrogation approach, in which proteome and transcriptome datasets from infection of both viruses in human lung epithelial cells are utilized to predict regulatory genes involved in the host response. We take advantage of a novel “crowd-based” approach to identify and combine ranking metrics that isolate genes/proteins likely related to the pathogenicity of SARS-CoV and influenza virus. Subsequently, a multivariate regression model is used to compare predicted lung epithelial regulatory influences with data derived from other respiratory virus infection models. We predicted a small set of regulatory factors with conserved behavior for consideration as important components of viral pathogenesis that might also serve as therapeutic targets for intervention. Our results demonstrate the utility of integrating diverse ‘omic datasets to predict and prioritize regulatory features conserved across multiple pathogen infection models.

  5. Epidemiological consequences of a pathogen having both virulent and avirulent modes of transmission: the case of rabbit haemorrhagic disease virus.

    PubMed Central

    White, P. J.; Norman, R. A.; Hudson, P. J.

    2002-01-01

    A number of pathogens cause chronic infection in survivors of acute disease and this is believed to be a common means of persistence, including for highly virulent agents. We present a model in which transmission from chronically infected hosts causes chronic infection in naive individuals, without causing acute disease--indeed 'protecting' against it. Thus the pathogen obtains the benefit of virulence (high transmission rate), but mitigates against the cost (high host mortality). Recent findings suggest that rabbit haemorrhagic disease virus (RHDV), a highly contagious and virulent pathogen, may also utilize this alternative, 'avirulent', mode of transmission. The model may resolve the paradox of how RHDV can be highly prevalent in some populations, in the absence of mortality. Differences in host demography determine whether avirulent transmission prevents large-scale mortality (as in most UK populations) or not. Other pathogens may exhibit similar behaviour and the implications for emerging diseases in general are discussed. PMID:12558352

  6. Adolescents and human immunodeficiency virus infection.

    PubMed

    Anderson, J R

    1992-12-01

    As of March 31, 1992, individuals 13 to 19 years of age had been diagnosed with acquired immunodeficiency syndrome; over one third were diagnosed in the past 2 years alone. Because of the long incubation period from initial infection to acquired immunodeficiency syndrome diagnosis, the majority of young adults with acquired immunodeficiency syndrome were probably initially infected as adolescents. In 1991, 34% of adolescents with acquired immunodeficiency syndrome were female, and their predominant mode of transmission was heterosexual contact. Human immunodeficiency virus seroprevalence studies of adolescents show a male-to-female ratio approaching 1:1, with many human immunodeficiency virus-infected adolescent women identifying none of the standard risk. Factors such as sexual and drug experimentation, risk taking, and sense of invulnerability so characteristic of adolescence put adolescents at special risk for human immunodeficiency virus. There is no published information on if or how clinical manifestations of human immunodeficiency virus disease in adolescents might differ from those seen in adults. Medical care should be broad-based and should include access to clinical trials for new drug treatments. General knowledge levels about acquired immunodeficiency syndrome are high among US adolescents, but behavioral changes have lagged behind. All adolescents should be targeted for intensive education about human immunodeficiency virus along with interventions designed to enhance their general coping, communication, and decision-making skills.

  7. Characterizing wild bird contact and seropositivity to highly pathogenic avian influenza A (H5N1) virus in Alaskan residents

    PubMed Central

    Reed, Carrie; Bruden, Dana; Byrd, Kathy K; Veguilla, Vic; Bruce, Michael; Hurlburt, Debby; Wang, David; Holiday, Crystal; Hancock, Kathy; Ortiz, Justin R; Klejka, Joe; Katz, Jacqueline M; Uyeki, Timothy M

    2014-01-01

    Background Highly pathogenic avian influenza A (HPAI) H5N1 viruses have infected poultry and wild birds on three continents with more than 600 reported human cases (59% mortality) since 2003. Wild aquatic birds are the natural reservoir for avian influenza A viruses, and migratory birds have been documented with HPAI H5N1 virus infection. Since 2005, clade 2.2 HPAI H5N1 viruses have spread from Asia to many countries. Objectives We conducted a cross-sectional seroepidemiological survey in Anchorage and western Alaska to identify possible behaviors associated with migratory bird exposure and measure seropositivity to HPAI H5N1. Methods We enrolled rural subsistence bird hunters and their families, urban sport hunters, wildlife biologists, and a comparison group without bird contact. We interviewed participants regarding their exposures to wild birds and collected blood to perform serologic testing for antibodies against a clade 2.2 HPAI H5N1 virus strain. Results Hunters and wildlife biologists reported exposures to wild migratory birds that may confer risk of infection with avian influenza A viruses, although none of the 916 participants had evidence of seropositivity to HPAI H5N1. Conclusions We characterized wild bird contact among Alaskans and behaviors that may influence risk of infection with avian influenza A viruses. Such knowledge can inform surveillance and risk communication surrounding HPAI H5N1 and other influenza viruses in a population with exposure to wild birds at a crossroads of intercontinental migratory flyways. PMID:24828535

  8. The neurobiology of varicella zoster virus infection

    PubMed Central

    Gilden, D.; Mahalingam, R.; Nagel, M. A.; Pugazhenthi, S.; Cohrs, R. J.

    2011-01-01

    Varicella zoster virus (VZV) is a neurotropic herpesvirus that infects nearly all humans. Primary infection usually causes chickenpox (varicella), after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. Although VZV cannot be isolated from human ganglia, nucleic acid hybridization and, later, polymerase chain reaction proved that VZV is latent in ganglia. Declining VZV-specific host immunity decades after primary infection allows virus to reactivate spontaneously, resulting in shingles (zoster) characterized by pain and rash restricted to 1-3 dermatomes. Multiple other serious neurological and ocular disorders also result from VZV reactivation. This review summarizes the current state of knowledge of the clinical and pathological complications of neurological and ocular disease produced by VZV reactivation, molecular aspects of VZV latency, VZV virology and VZV-specific immunity, the role of apoptosis in VZV-induced cell death, and the development of an animal model provided by simian varicella virus infection of monkeys. PMID:21342215

  9. Pathogenesis of Machupo virus infection in primates.

    PubMed

    Eddy, G A; Scott, S K; Wagner, F S; Brand, O M

    1975-01-01

    Experimental Machupo virus infection of rhesus and cynomolgus monkeys produced a severe illness consisting of an initial clinical phase and a later neurological phase. Cumulative mortality during the two phases was 80% and 95% respectively. Attempts to alter the pathogenesis with decomplementation or immunosuppression resulted in earlier deaths of the monkeys.

  10. Fatal canine distemper virus infection of giant pandas in China

    PubMed Central

    Feng, Na; Yu, Yicong; Wang, Tiecheng; Wilker, Peter; Wang, Jianzhong; Li, Yuanguo; Sun, Zhe; Gao, Yuwei; Xia, Xianzhu

    2016-01-01

    We report an outbreak of canine distemper virus (CDV) infection among endangered giant pandas (Ailuropoda melanoleuca). Five of six CDV infected giant pandas died. The surviving giant panda was previously vaccinated against CDV. Genomic sequencing of CDV isolated from one of the infected pandas (giant panda/SX/2014) suggests it belongs to the Asia-1 cluster. The hemagglutinin protein of the isolated virus and virus sequenced from lung samples originating from deceased giant pandas all possessed the substitutions V26M, T213A, K281R, S300N, P340Q, and Y549H. The presence of the Y549H substitution is notable as it is found at the signaling lymphocytic activation molecule (SLAM) receptor-binding site and has been implicated in the emergence of highly pathogenic CDV and host switching. These findings demonstrate that giant pandas are susceptible to CDV and suggest that surveillance and vaccination among all captive giant pandas are warranted to support conservation efforts for this endangered species. PMID:27310722

  11. Fatal canine distemper virus infection of giant pandas in China.

    PubMed

    Feng, Na; Yu, Yicong; Wang, Tiecheng; Wilker, Peter; Wang, Jianzhong; Li, Yuanguo; Sun, Zhe; Gao, Yuwei; Xia, Xianzhu

    2016-01-01

    We report an outbreak of canine distemper virus (CDV) infection among endangered giant pandas (Ailuropoda melanoleuca). Five of six CDV infected giant pandas died. The surviving giant panda was previously vaccinated against CDV. Genomic sequencing of CDV isolated from one of the infected pandas (giant panda/SX/2014) suggests it belongs to the Asia-1 cluster. The hemagglutinin protein of the isolated virus and virus sequenced from lung samples originating from deceased giant pandas all possessed the substitutions V26M, T213A, K281R, S300N, P340Q, and Y549H. The presence of the Y549H substitution is notable as it is found at the signaling lymphocytic activation molecule (SLAM) receptor-binding site and has been implicated in the emergence of highly pathogenic CDV and host switching. These findings demonstrate that giant pandas are susceptible to CDV and suggest that surveillance and vaccination among all captive giant pandas are warranted to support conservation efforts for this endangered species. PMID:27310722

  12. Fatal canine distemper virus infection of giant pandas in China.

    PubMed

    Feng, Na; Yu, Yicong; Wang, Tiecheng; Wilker, Peter; Wang, Jianzhong; Li, Yuanguo; Sun, Zhe; Gao, Yuwei; Xia, Xianzhu

    2016-06-16

    We report an outbreak of canine distemper virus (CDV) infection among endangered giant pandas (Ailuropoda melanoleuca). Five of six CDV infected giant pandas died. The surviving giant panda was previously vaccinated against CDV. Genomic sequencing of CDV isolated from one of the infected pandas (giant panda/SX/2014) suggests it belongs to the Asia-1 cluster. The hemagglutinin protein of the isolated virus and virus sequenced from lung samples originating from deceased giant pandas all possessed the substitutions V26M, T213A, K281R, S300N, P340Q, and Y549H. The presence of the Y549H substitution is notable as it is found at the signaling lymphocytic activation molecule (SLAM) receptor-binding site and has been implicated in the emergence of highly pathogenic CDV and host switching. These findings demonstrate that giant pandas are susceptible to CDV and suggest that surveillance and vaccination among all captive giant pandas are warranted to support conservation efforts for this endangered species.

  13. Reduction of high pathogenicity avian influenza virus in eggs from chickens once or twice vaccinated with an oil-emulsified inactivated H5 avian influenza vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The negative impact of high pathogenicity avian influenza virus (HPAIV) infection on egg production and deposition of virus in eggs, as well as any protective effect of vaccination, is unknown. Individually housed non-vaccinated, sham-vaccinated and inactivated H5N9 vaccinated once or twice adult Wh...

  14. Changes in adaptation of H5N2 highly pathogenic avian influenza H5 clade 2.3.4.4 viruses in chickens and mallards

    Technology Transfer Automated Retrieval System (TEKTRAN)

    H5N2 highly pathogenic avian influenza (HPAI) viruses caused a severe poultry outbreak in the United States (U.S.) during 2015. In order to examine changes in adaptation of this viral lineage, the infectivity, transmission and pathogenesis of poultry H5N2 viruses was investigated in chickens and mal...

  15. A multiplex PCR for simultaneous detection of classical swine fever virus, African swine fever virus, highly pathogenic porcine reproductive and respiratory syndrome virus, porcine reproductive and respiratory syndrome virus and pseudorabies in swines.

    PubMed

    Hu, L; Lin, X Y; Yang, Z X; Yao, X P; Li, G L; Peng, S Z; Wang, Y

    2015-01-01

    In this assay, we developed and evaluated a multiplex PCR (mPCR) for its ability in detecting multiple infections of swine simultaneously. Four pairs of primers were used to detect five viruses. Specific primers were designed for classical swine fever virus (CSFV), African swine fever virus (ASFV) and pseudorabies (PRV). A pair of primers was designed prudently for two different types of porcine reproductive and respiratory syndrome virus that respectively were porcine reproductive and respiratory syndrome virus (PRRSV), highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV). The detection limits of the mPCR were 1.09 × 10⁴, 1.50 × 10³, 2.10 × 10³, 1.30 × 10³ and 8.97 × 10² copies/reaction for CSFV, ASFV, HP-PRRSV, PRRSV and PRV, respectively. A total of 49 clinical specimens were tested by the mPCR, and the result showed that co-infection by two or three viruses was 51%. In conclusion, the PCR is a useful tool for clinical diagnosis of not only single infections but also mixed infections in swines. PMID:26812812

  16. Cryptococcus gattii: an emerging fungal pathogen infecting humans and animals

    PubMed Central

    Byrnes, Edmond J.; Bartlett, Karen H.; Perfect, John R.; Heitman, Joseph

    2012-01-01

    Infectious fungi are among a broad group of microbial pathogens that has and continues to emerge concomitantly due to the global AIDS pandemic as well as an overall increase of patients with compromised immune systems. In addition, many pathogens have been emerging and reemerging, causing disease in both individuals who have an identifiable immune defect and those who do not. The fungal pathogen Cryptococcus gattii can infect individuals with and without an identifiable immune defect, with a broad geographic range including both endemic areas and emerging outbreak regions. Infections in patients and animals can be severe and often fatal if untreated. We review the molecular epidemiology, population structure, clinical manifestations, and ecological niche of this emerging pathogen. PMID:21684347

  17. Viruses as potential pathogenic agents in systemic lupus erythematosus.

    PubMed

    Nelson, P; Rylance, P; Roden, D; Trela, M; Tugnet, N

    2014-05-01

    Genetic and environmental factors appear to contribute to the pathogenesis of systemic lupus erythematosus (SLE). Viral infections have been reported to be associated with the disease. A number of exogenous viruses have been linked to the pathogenesis of SLE, of which Epstein-Barr virus (EBV) has the most evidence of an aetiological candidate. In addition, human endogenous retroviruses (HERV), HRES-1, ERV-3, HERV-E 4-1, HERV-K10 and HERV-K18 have also been implicated in SLE. HERVs are incorporated into human DNA, and thus can be inherited. HERVs may trigger an autoimmune reaction through molecular mimicry, since homology of amino acid sequences between HERV proteins and SLE autoantigens has been demonstrated. These viruses can also be influenced by oestrogen, DNA hypomethylation, and ultraviolet light (UVB) exposure which have been shown to enhance HERV activation or expression. Viral infection, or other environmental factors, could induce defective apoptosis, resulting in loss of immune tolerance. Further studies in SLE and other autoimmune diseases are needed to elucidate the contribution of both exogenous and endogenous viruses in the development of autoimmunity. If key peptide sequences could be identified as molecular mimics between viruses and autoantigens, then this might offer the possibility of the development of blocking peptides or antibodies as therapeutic agents in SLE and other autoimmune conditions.

  18. Filter-feeding bivalves can remove avian influenza viruses from water and reduce infectivity

    PubMed Central

    Faust, Christina; Stallknecht, David; Swayne, David; Brown, Justin

    2009-01-01

    Avian influenza (AI) viruses are believed to be transmitted within wild aquatic bird populations through an indirect faecal–oral route involving contaminated water. This study examined the influence of filter-feeding bivalves, Corbicula fluminea, on the infectivity of AI virus in water. Clams were placed into individual flasks with distilled water inoculated 1:100 with a low pathogenic (LP) AI virus (A/Mallard/MN/190/99 (H3N8)). Viral titres in water with clams were significantly lower at 24 and 48 h post-inoculation compared to LPAI-infected water without clams. To determine whether clams affected the infectivity of AI viruses, 18 wood ducks (Aix sponsa) were divided into test groups and inoculated with a variety of treatments of clam supernatants, whole clams and water exposed to a high pathogenic (HP) AI (A/whooper swan/Mongolia/244/05 (H5N1)). None of the wood ducks inoculated with HPAI-infected water that was filtered by clams or that was inoculated with or fed tissue from these clams exhibited morbidity or mortality. All wood ducks exposed to either HPAI-infected water without clams or the original viral inoculum died. These results indicate that filter-feeding bivalves can remove and reduce the infectivity of AI viruses in water and demonstrate the need to examine biotic environmental factors that can influence AI virus transmission. PMID:19656788

  19. Clearance of persistent hepatitis C virus infection using a claudin-1-targeting monoclonal antibody

    PubMed Central

    Mailly, Laurent; Wilson, Garrick K.; Aubert, Philippe; Duong, François H. T.; Calabrese, Diego; Leboeuf, Céline; Fofana, Isabel; Thumann, Christine; Bandiera, Simonetta; Lütgehetmann, Marc; Volz, Tassilo; Davis, Christopher; Harris, Helen J.; Mee, Christopher J.; Girardi, Erika; Chane-Woon-Ming, Béatrice; Ericsson, Maria; Fletcher, Nicola; Bartenschlager, Ralf; Pessaux, Patrick; Vercauteren, Koen; Meuleman, Philip; Villa, Pascal; Kaderali, Lars; Pfeffer, Sébastien; Heim, Markus H.; Neunlist, Michel; Zeisel, Mirjam B.; Dandri, Maura; McKeating, Jane A.; Robinet, Eric; Baumert, Thomas F.

    2015-01-01

    Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and cancer1. Cell entry of HCV2 and other pathogens3-5 is mediated by tight junction (TJ) proteins, but successful therapeutic targeting of TJ proteins has not been reported yet. Using a human liver-chimeric mouse model6 we show that a monoclonal antibody specific for TJ protein claudin-17 eliminates chronic HCV infection without detectable toxicity. This antibody inhibits HCV entry, cell-cell transmission and virus-induced signaling events. Antibody treatment reduces the number of HCV-infected hepatocytes in vivo, highlighting the need for de novo infection via host entry factors to maintain chronic infection. In summary, we demonstrate that an antibody targeting a virus receptor can cure chronic viral infection and uncover TJ proteins as targets for antiviral therapy. PMID:25798937

  20. Skin manifestations of West Nile virus infection.

    PubMed

    Del Giudice, P; Schuffenecker, I; Zeller, H; Grelier, M; Vandenbos, F; Dellamonica, P; Counillon, E

    2005-01-01

    West Nile virus (WNV) infection is a potentially lethal arbovirus infection. Many notable outbreaks have occurred during the last few years throughout the world, including Europe and the USA. The severity of the disease is mainly related to the neurological complications. A maculopapular exanthema is reported as a clinical sign of the disease. Recently an outbreak of WNV infection occurred in southern France. Three patients out of 6 had a similar skin roseola-like eruption. The cluster of 3 cases of similar febrile roseola of unexplained cause during the same week led to the diagnosis of the first WNV human outbreak in France for 40 years. PMID:16286745

  1. Human Bocavirus: Passenger or Pathogen in Acute Respiratory Tract Infections?

    PubMed Central

    Schildgen, Oliver; Müller, Andreas; Allander, Tobias; Mackay, Ian M.; Völz, Sebastian; Kupfer, Bernd; Simon, Arne

    2008-01-01

    Summary: Human bocavirus (HBoV) is a newly identified virus tentatively assigned to the family Parvoviridae, subfamily Parvovirinae, genus Bocavirus. HBoV was first described in 2005 and has since been detected in respiratory tract secretions worldwide. Herein we review the literature on HBoV and discuss the biology and potential clinical impact of this virus. Most studies have been PCR based and performed on patients with acute respiratory symptoms, from whom HBoV was detected in 2 to 19% of the samples. HBoV-positive samples have been derived mainly from infants and young children. HBoV DNA has also been detected in the blood of patients with respiratory tract infection and in fecal samples of patients with diarrhea with or without concomitant respiratory symptoms. A characteristic feature of HBoV studies is the high frequency of coinciding detections, or codetections, with other viruses. Available data nevertheless indicate a statistical association between HBoV and acute respiratory tract disease. We present a model incorporating these somewhat contradictory findings and suggest that primary HBoV infection causes respiratory tract symptoms which can be followed by prolonged low-level virus shedding in the respiratory tract. Detection of the virus in this phase will be facilitated by other infections, either simply via increased sample cell count or via reactivation of HBoV, leading to an increased detection frequency of HBoV during other virus infections. We conclude that the majority of available HBoV studies are limited by the sole use of PCR diagnostics on respiratory tract secretions, addressing virus prevalence but not disease association. The ability to detect primary infection through the development of improved diagnostic methods will be of great importance for future studies seeking to assign a role for HBoV in causing respiratory illnesses. PMID:18400798

  2. Activation of c-jun N-Terminal Kinase upon Influenza A Virus (IAV) Infection Is Independent of Pathogen-Related Receptors but Dependent on Amino Acid Sequence Variations of IAV NS1

    PubMed Central

    Nacken, Wolfgang; Anhlan, Darisuren; Hrincius, Eike R.; Mostafa, Ahmed; Wolff, Thorsten; Sadewasser, Anne; Pleschka, Stephan; Ehrhardt, Christina

    2014-01-01

    ABSTRACT A hallmark cell response to influenza A virus (IAV) infections is the phosphorylation and activation of c-jun N-terminal kinase (JNK). However, so far it is not fully clear which molecules are involved in the activation of JNK upon IAV infection. Here, we report that the transfection of influenza viral-RNA induces JNK in a retinoic acid-inducible gene I (RIG-I)-dependent manner. However, neither RIG-I-like receptors nor MyD88-dependent Toll-like receptors were found to be involved in the activation of JNK upon IAV infection. Viral JNK activation may be blocked by addition of cycloheximide and heat shock protein inhibitors during infection, suggesting that the expression of an IAV-encoded protein is responsible for JNK activation. Indeed, the overexpression of nonstructural protein 1 (NS1) of certain IAV subtypes activated JNK, whereas those of some other subtypes failed to activate JNK. Site-directed mutagenesis experiments using N