Sample records for viral pathogen ranavirus

  1. Recent host-shifts in ranaviruses: signatures of positive selection in the viral genome

    PubMed Central

    Cannatella, David C.; Hillis, David M.; Sawyer, Sara L.

    2013-01-01

    Ranaviruses have been implicated in recent declines in global amphibian populations. Compared with the family Iridoviridae, to which the genus Ranavirus belongs, ranaviruses have a wide host range in that species/strains are known to infect fish, amphibians and reptiles, presumably due to recent host-switching events. We used eight sequenced ranavirus genomes and two selection-detection methods (site based and branch based) to identify genes that exhibited signatures of positive selection, potentially due to the selective pressures at play during host switching. We found evidence of positive selection acting on four genes via the site-based method, three of which were newly acquired genes unique to ranavirus genomes. Using the branch-based method, we identified eight additional candidate genes that exhibited signatures of dN/dS (non-synonymous/synonymous substitution rate) >1 in the clade where intense host switching had occurred. We found that these branch-specific patterns of elevated dN/dS were enriched in a small group of viral genes that have been acquired most recently in the ranavirus genome, compared with core genes that are shared among all members of the family Iridoviridae. Our results suggest that the group of newly acquired genes in the ranavirus genome may have undergone recent adaptive changes that have facilitated interspecies and interclass host switching. PMID:23784445

  2. Immune Evasion Strategies of Ranaviruses and Innate Immune Responses to These Emerging Pathogens

    PubMed Central

    Grayfer, Leon; Andino, Francisco De Jesús; Chen, Guangchun; Chinchar, Gregory V.; Robert, Jacques

    2012-01-01

    Ranaviruses (RV, Iridoviridae) are large double-stranded DNA viruses that infect fish, amphibians and reptiles. For ecological and commercial reasons, considerable attention has been drawn to the increasing prevalence of ranaviral infections of wild populations and in aquacultural settings. Importantly, RVs appear to be capable of crossing species barriers of numerous poikilotherms, suggesting that these pathogens possess a broad host range and potent immune evasion mechanisms. Indeed, while some of the 95–100 predicted ranavirus genes encode putative evasion proteins (e.g., vIF?, vCARD), roughly two-thirds of them do not share significant sequence identity with known viral or eukaryotic genes. Accordingly, the investigation of ranaviral virulence and immune evasion strategies is promising for elucidating potential antiviral targets. In this regard, recombination-based technologies are being employed to knock out gene candidates in the best-characterized RV member, Frog Virus (FV3). Concurrently, by using animal infection models with extensively characterized immune systems, such as the African clawed frog, Xenopus laevis, it is becoming evident that components of innate immunity are at the forefront of virus-host interactions. For example, cells of the macrophage lineage represent important combatants of RV infections while themselves serving as targets for viral infection, maintenance and possibly dissemination. This review focuses on the recent advances in the understanding of the RV immune evasion strategies with emphasis on the roles of the innate immune system in ranaviral infections. PMID:22852041

  3. The Amphibian (Xenopus laevis) Type I Interferon Response to Frog Virus 3: New Insight into Ranavirus Pathogenicity

    PubMed Central

    Grayfer, Leon; De Jesús Andino, Francisco

    2014-01-01

    ABSTRACT The increasing prevalence of ranavirus (RV; Iridoviridae) infections of wild and commercially maintained aquatic species is raising considerable concerns. While Xenopus laevis is the leading model for studies of immunity to RV, amphibian antiviral interferon (IFN) responses remain largely uncharacterized. Accordingly, an X. laevis type I interferon was identified, the expression of the gene for this IFN was examined in RV (frog virus 3 [FV3])-infected tadpoles and adult frogs by quantitative PCR, and a recombinant form of this molecule (recombinant X. laevis interferon [rXlIFN]) was produced for the purpose of functional studies. This rXlIFN protected the kidney-derived A6 cell line and tadpoles against FV3 infection, decreasing the infectious viral burdens in both cases. Adult frogs are naturally resistant to FV3 and clear the infection within a few weeks, whereas tadpoles typically succumb to this virus. Hence, as predicted, virus-infected adult X. laevis frogs exhibited significantly more robust FV3-elicited IFN gene expression than tadpoles; nevertheless, they also tolerated substantially greater viral burdens following infection. Although tadpole stimulation with rXlIFN prior to FV3 challenge markedly impaired viral replication and viral burdens, it only transiently extended tadpole survival and did not prevent the eventual mortality of these animals. Furthermore, histological analysis revealed that despite rXlIFN treatment, infected tadpoles had considerable organ damage, including disrupted tissue architecture and extensive necrosis and apoptosis. Conjointly, these findings indicate a critical protective role for the amphibian type I IFN response during ranaviral infections and suggest that these viruses are more pathogenic to tadpole hosts than was previously believed, causing extensive and fatal damage to multiple organs, even at very low titers. IMPORTANCE Ranavirus infections are threatening wild and commercially maintained aquatic species. The amphibian Xenopus laevis is extensively utilized as an infection model for studying ranavirus-host immune interactions. However, little is known about amphibian antiviral immunity and, specifically, type I interferons (IFNs), which are central to the antiviral defenses of other vertebrates. Accordingly, we identified and characterized an X. laevis type I interferon in the context of infection with the ranavirus frog virus 3 (FV3). FV3-infected adult frogs displayed more robust IFN gene expression than tadpoles, possibly explaining why they typically clear FV3 infections, whereas tadpoles succumb to them. Pretreatment with a recombinant X. laevis IFN (rXlIFN) substantially reduced viral replication and infectious viral burdens in a frog kidney cell line and in tadpoles. Despite reducing FV3 loads and extending the mean survival time, rXlIFN treatments failed to prevent tadpole tissue damage and mortality. Thus, FV3 is more pathogenic than was previously believed, even at very low titers. PMID:24623410

  4. Leafhopper viral pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four newly discovered viral pathogens in leafhopper vectors of Pierce’s disease of grapes, have been shown to replicate in sharpshooter leafhoppers; the glassy-winged sharpshooter, GWSS, Homalodisca vitripennis, and Oncometopia nigricans (Hemiptera: Cicadellidae). The viruses were classified as memb...

  5. Detection of the emerging amphibian pathogens Batrachochytrium dendrobatidis and ranavirus in Russia.

    PubMed

    Reshetnikov, Andrey N; Chestnut, Tara; Brunner, Jesse L; Charles, Kaylene; Nebergall, Emily E; Olson, Deanna H

    2014-08-11

    In a population of the European common toad Bufo bufo from a rural pond in the region of Lake Glubokoe Regional Reserve in Moscow province, Russia, unexplained mass mortality events involving larvae and metamorphs have been observed over a monitoring period of >20 yr. We tested toads from this and a nearby site for the emerging amphibian pathogens Batrachochytrium dendrobatidis (Bd) and ranavirus (Rv). Both pathogens were detected, and at the rural pond site, with the above-noted losses and decline in toad breeding success, 40% of B. bufo metamorphs were Bd positive, 46% were Rv positive and 20% were co-infected with both pathogens. Toad metamorphs from a neighbouring water body were also Bd and Rv positive (25 and 55%, respectively). This is the first confirmation of these pathogens in Russia. Questions remain as to the origins of these pathogens in Russia and their roles in documented mass mortality events. PMID:25114047

  6. Amphibian pathogens at northern latitudes: presence of chytrid fungus and ranavirus in northeastern Canada.

    PubMed

    D'Aoust-Messier, Andrée-Michelle; Echaubard, Pierre; Billy, Vincent; Lesbarrères, David

    2015-03-01

    Infections by the fungal pathogen Batrachochytrium dendrobatidis (Bd) and members of the genus Ranavirus (Rv) are increasingly reported as significant determinants of amphibian population die-offs. The complexity associated with their transmission and spatial distribution leads to an increase in demand for comprehensive reporting systems and global mapping of their distribution. Here, we document the distribution of these 2 pathogens in a remote northern temperate lowland where environmental sensitivity is high, providing important insight into the pathogens' natural history and infection patterns. Wood frog Lithobates sylvaticus tissues were collected from the James Bay area in northeastern Canada and were screened for the presence of Bd and Rv using conventional and real-time PCR. Both pathogens were present in the study area, which is the northernmost record in eastern North America. Interestingly, different patterns of distribution were observed between the eastern and western coasts of James Bay, suggesting differences in the spatial and transmission dynamics for each pathogen. Anthropogenic introduction may still influence the distribution patterns observed, even at these latitudes. The presence of infections in this remote area also raises further questions on the risk these pathogens pose to northern amphibian communities. We encourage further research in remote locations for a better understanding of these pathogens, their transmission dynamics, and especially their respective impacts on amphibian populations worldwide. PMID:25751857

  7. Phylogeny and Differentiation of Reptilian and Amphibian Ranaviruses Detected in Europe

    PubMed Central

    Stöhr, Anke C.; López-Bueno, Alberto; Blahak, Silvia; Caeiro, Maria F.; Rosa, Gonçalo M.; Alves de Matos, António Pedro; Martel, An; Alejo, Alí; Marschang, Rachel E.

    2015-01-01

    Ranaviruses in amphibians and fish are considered emerging pathogens and several isolates have been extensively characterized in different studies. Ranaviruses have also been detected in reptiles with increasing frequency, but the role of reptilian hosts is still unclear and only limited sequence data has been provided. In this study, we characterized a number of ranaviruses detected in wild and captive animals in Europe based on sequence data from six genomic regions (major capsid protein (MCP), DNA polymerase (DNApol), ribonucleoside diphosphate reductase alpha and beta subunit-like proteins (RNR-? and -?), viral homolog of the alpha subunit of eukaryotic initiation factor 2, eIF-2? (vIF-2?) genes and microsatellite region). A total of ten different isolates from reptiles (tortoises, lizards, and a snake) and four ranaviruses from amphibians (anurans, urodeles) were included in the study. Furthermore, the complete genome sequences of three reptilian isolates were determined and a new PCR for rapid classification of the different variants of the genomic arrangement was developed. All ranaviruses showed slight variations on the partial nucleotide sequences from the different genomic regions (92.6–100%). Some very similar isolates could be distinguished by the size of the band from the microsatellite region. Three of the lizard isolates had a truncated vIF-2? gene; the other ranaviruses had full-length genes. In the phylogenetic analyses of concatenated sequences from different genes (3223 nt/10287 aa), the reptilian ranaviruses were often more closely related to amphibian ranaviruses than to each other, and most clustered together with previously detected ranaviruses from the same geographic region of origin. Comparative analyses show that among the closely related amphibian-like ranaviruses (ALRVs) described to date, three recently split and independently evolving distinct genetic groups can be distinguished. These findings underline the wide host range of ranaviruses and the emergence of pathogen pollution via animal trade of ectothermic vertebrates. PMID:25706285

  8. Asian citrus psyllid viral pathogen

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A newly discovered viral pathogen of Asian citrus psyllid, AsCP, Diaphorina citri, Kuwayama (Psyllidae: Hemiptera) was classified as a Reoviridae. This virus may serve as a biological control agent for AsCP. The AsCP is an efficient vector of the plant-infecting bacterium (Candidatus Liberibacter as...

  9. Genome architecture changes and major gene variations of Andrias davidianus ranavirus (ADRV).

    PubMed

    Chen, Zhongyuan; Gui, Jianfang; Gao, Xiaochan; Pei, Chao; Hong, Yijiang; Zhang, Qiya

    2013-01-01

    Ranaviruses are emerging pathogens that have led to global impact and public concern. As a rarely endangered species and the largest amphibian in the world, the Chinese giant salamander, Andrias davidianus, has recently undergone outbreaks of epidemic diseases with high mortality. In this study, we isolated and identified a novel ranavirus from the Chinese giant salamanders that exhibited systemic hemorrhage and swelling syndrome with high death rate in China during May 2011 to August 2012. The isolate, designated Andrias davidianus ranavirus (ADRV), not only could induce cytopathic effects in different fish cell lines and yield high viral titers, but also caused severely hemorrhagic lesions and resulted in 100% mortality in experimental infections of salamanders. The complete genome of ADRV was sequenced and compared with other sequenced amphibian ranaviruses. Gene content and phylogenetic analyses revealed that ADRV should belong to an amphibian subgroup in genus Ranavirus, and is more closely related to frog ranaviruses than to other salamander ranaviruses. Homologous gene comparisons show that ADRV contains 99%, 97%, 94%, 93% and 85% homologues in RGV, FV3, CMTV, TFV and ATV genomes respectively. In addition, several variable major genes, such as duplicate US22 family-like genes, viral eukaryotic translation initiation factor 2 alpha gene and novel 75L gene with both motifs of nuclear localization signal (NLS) and nuclear export signal (NES), were predicted to contribute to pathogen virulence and host susceptibility. These findings confirm the etiologic role of ADRV in epidemic diseases of Chinese giant salamanders, and broaden our understanding of evolutionary emergence of ranaviruses. PMID:24143877

  10. Genome architecture changes and major gene variations of Andrias davidianus ranavirus (ADRV)

    PubMed Central

    2013-01-01

    Ranaviruses are emerging pathogens that have led to global impact and public concern. As a rarely endangered species and the largest amphibian in the world, the Chinese giant salamander, Andrias davidianus, has recently undergone outbreaks of epidemic diseases with high mortality. In this study, we isolated and identified a novel ranavirus from the Chinese giant salamanders that exhibited systemic hemorrhage and swelling syndrome with high death rate in China during May 2011 to August 2012. The isolate, designated Andrias davidianus ranavirus (ADRV), not only could induce cytopathic effects in different fish cell lines and yield high viral titers, but also caused severely hemorrhagic lesions and resulted in 100% mortality in experimental infections of salamanders. The complete genome of ADRV was sequenced and compared with other sequenced amphibian ranaviruses. Gene content and phylogenetic analyses revealed that ADRV should belong to an amphibian subgroup in genus Ranavirus, and is more closely related to frog ranaviruses than to other salamander ranaviruses. Homologous gene comparisons show that ADRV contains 99%, 97%, 94%, 93% and 85% homologues in RGV, FV3, CMTV, TFV and ATV genomes respectively. In addition, several variable major genes, such as duplicate US22 family-like genes, viral eukaryotic translation initiation factor 2 alpha gene and novel 75L gene with both motifs of nuclear localization signal (NLS) and nuclear export signal (NES), were predicted to contribute to pathogen virulence and host susceptibility. These findings confirm the etiologic role of ADRV in epidemic diseases of Chinese giant salamanders, and broaden our understanding of evolutionary emergence of ranaviruses. PMID:24143877

  11. Ecopathology of Ranaviruses Infecting Amphibians

    PubMed Central

    Miller, Debra; Gray, Matthew; Storfer, Andrew

    2011-01-01

    Ranaviruses are capable of infecting amphibians from at least 14 families and over 70 individual species. Ranaviruses infect multiple cell types, often culminating in organ necrosis and massive hemorrhaging. Subclinical infections have been documented, although their role in ranavirus persistence and emergence remains unclear. Water is an effective transmission medium for ranaviruses, and survival outside the host may be for significant duration. In aquatic communities, amphibians, reptiles and fish may serve as reservoirs. Controlled studies have shown that susceptibility to ranavirus infection and disease varies among amphibian species and developmental stages, and likely is impacted by host-pathogen coevolution, as well as, exogenous environmental factors. Field studies have demonstrated that the likelihood of epizootics is increased in areas of cattle grazing, where aquatic vegetation is sparse and water quality is poor. Translocation of infected amphibians through commercial trade (e.g., food, fish bait, pet industry) contributes to the spread of ranaviruses. Such introductions may be of particular concern, as several studies report that ranaviruses isolated from ranaculture, aquaculture, and bait facilities have greater virulence (i.e., ability to cause disease) than wild-type isolates. Future investigations should focus on the genetic basis for pathogen virulence and host susceptibility, ecological and anthropogenic mechanisms contributing to emergence, and vaccine development for use in captive populations and species reintroduction programs. PMID:22163349

  12. Ranavirus outbreaks in amphibian populations of northern Idaho

    USGS Publications Warehouse

    Russell, Danelle M.; Goldberg, Caren S.; Sprague, Laura; Waits, Lisette P.; Green, D. Earl; Schuler, Krysten L.; Rosenblum, Erica Bree

    2011-01-01

    Ranavirus outbreaks, caused by pathogens in the genus Ranavirus (Family Iridoviridae), were the largest single cause of reported amphibian mass mortality events in the United States from 1996–2001 (Green et al. 2002). Mortality events associated with ranaviruses have been documented on five continents and throughout the latitudes and elevations where amphibians occur (Gray et al. 2009). However, the threat of ranaviruses to amphibian and reptile populations in specific regions is still largely unknown (Chinchar 2002; Gray et al. 2009).

  13. Transmission of ranavirus between ectothermic vertebrate hosts.

    PubMed

    Brenes, Roberto; Gray, Matthew J; Waltzek, Thomas B; Wilkes, Rebecca P; Miller, Debra L

    2014-01-01

    Transmission is an essential process that contributes to the survival of pathogens. Ranaviruses are known to infect different classes of lower vertebrates including amphibians, fishes and reptiles. Differences in the likelihood of infection among ectothermic vertebrate hosts could explain the successful yearlong persistence of ranaviruses in aquatic environments. The goal of this study was to determine if transmission of a Frog Virus 3 (FV3)-like ranavirus was possible among three species from different ectothermic vertebrate classes: Cope's gray treefrog (Hyla chrysoscelis) larvae, mosquito fish (Gambusia affinis), and red-eared slider (Trachemys scripta elegans). We housed individuals previously exposed to the FV3-like ranavirus with naïve (unexposed) individuals in containers divided by plastic mesh screen to permit water flow between subjects. Our results showed that infected gray treefrog larvae were capable of transmitting ranavirus to naïve larval conspecifics and turtles (60% and 30% infection, respectively), but not to fish. Also, infected turtles and fish transmitted ranavirus to 50% and 10% of the naïve gray treefrog larvae, respectively. Nearly all infected amphibians experienced mortality, whereas infected turtles and fish did not die. Our results demonstrate that ranavirus can be transmitted through water among ectothermic vertebrate classes, which has not been reported previously. Moreover, fish and reptiles might serve as reservoirs for ranavirus given their ability to live with subclinical infections. Subclinical infections of ranavirus in fish and aquatic turtles could contribute to the pathogen's persistence, especially when highly susceptible hosts like amphibians are absent as a result of seasonal fluctuations in relative abundance. PMID:24667325

  14. Transmission of Ranavirus between Ectothermic Vertebrate Hosts

    PubMed Central

    Brenes, Roberto; Gray, Matthew J.; Waltzek, Thomas B.; Wilkes, Rebecca P.; Miller, Debra L.

    2014-01-01

    Transmission is an essential process that contributes to the survival of pathogens. Ranaviruses are known to infect different classes of lower vertebrates including amphibians, fishes and reptiles. Differences in the likelihood of infection among ectothermic vertebrate hosts could explain the successful yearlong persistence of ranaviruses in aquatic environments. The goal of this study was to determine if transmission of a Frog Virus 3 (FV3)-like ranavirus was possible among three species from different ectothermic vertebrate classes: Cope’s gray treefrog (Hyla chrysoscelis) larvae, mosquito fish (Gambusia affinis), and red-eared slider (Trachemys scripta elegans). We housed individuals previously exposed to the FV3-like ranavirus with naïve (unexposed) individuals in containers divided by plastic mesh screen to permit water flow between subjects. Our results showed that infected gray treefrog larvae were capable of transmitting ranavirus to naïve larval conspecifics and turtles (60% and 30% infection, respectively), but not to fish. Also, infected turtles and fish transmitted ranavirus to 50% and 10% of the naïve gray treefrog larvae, respectively. Nearly all infected amphibians experienced mortality, whereas infected turtles and fish did not die. Our results demonstrate that ranavirus can be transmitted through water among ectothermic vertebrate classes, which has not been reported previously. Moreover, fish and reptiles might serve as reservoirs for ranavirus given their ability to live with subclinical infections. Subclinical infections of ranavirus in fish and aquatic turtles could contribute to the pathogen’s persistence, especially when highly susceptible hosts like amphibians are absent as a result of seasonal fluctuations in relative abundance. PMID:24667325

  15. Viral pathogens of Glassy-winged sharpshooters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A newly discovered viral pathogen to the glassy-winged sharpshooter, GWSS, Homalodisca vitripennis, (Hemiptera: Cicadellidae) was characterized. The virus genome was sequenced, and the path of infection into the leafhopper was determined to be through the midgut tissues. The virus occurs naturally i...

  16. Isolation and characterization of a ranavirus from koi, Cyprinus carpio L., experiencing mass mortalities in India.

    PubMed

    George, M R; John, K R; Mansoor, M M; Saravanakumar, R; Sundar, P; Pradeep, V

    2015-04-01

    We investigated mass mortalities of koi, Cyprinus carpio Linnaeus, 1758, experienced in South Indian fish farms by virus isolation, electron microscopy, PCR detection, sequencing of capsid protein gene and transmission studies. Samples of moribund koi brought to the laboratory suffered continuous mortality exhibiting swimming abnormalities, intermittent surfacing and skin darkening. Irido-like virus was isolated from the infected fish in the indigenous snakehead kidney cell line (SNKD2a). Icosahedral virus particles of 100 to 120 nm were observed in the infected cell cultures, budding from the cell membrane. Virus transmission and pathogenicity studies revealed that horizontal transmission occurred associated with mortality. PCR analysis of infected fish and cell cultures confirmed the presence of Ranavirus capsid protein sequences. Sequence analysis of the major capsid protein gene showed an identity of 99.9% to that of largemouth bass virus isolated from North America. Detection and successful isolation of this viral agent becomes the first record of isolation of a virus resembling Santee-Cooper Ranavirus from a koi and from India. We propose the name koi ranavirus to this agent. PMID:24720625

  17. Matthew J. Gray Ranaviruses

    E-print Network

    Gray, Matthew

    support these claims? #12;History of Ranavirus Die-offs First Isolated: ·Dr. Allan Granoff ·Rana pipiens Hylidae Bufonidae Ambystomatidae Salamandridae Norman Wells, NWT Uncommon Lithobates sylvaticus #12;Are

  18. Susceptibility of pike Esox lucius to a panel of Ranavirus isolates.

    PubMed

    Jensen, Britt Bang; Ersbøll, Annette Kjaer; Ariel, Ellen

    2009-02-25

    In order to study the pathogenicity of ranaviruses to a wild European freshwater fish species, pike Esox lucius fry were challenged with the following Ranavirus isolates: epizootic haematopoietic necrosis virus (EHNV), European sheatfish virus (ESV), European catfish virus (ECV), pike-perch iridovirus (PPIV), New Zealand eel virus (NZeelV) and frog virus 3 (FV3). The fry were infected using bath challenge at 12 and 22 degrees C. Significant mortalities were observed at 12 degrees C for EHNV, ESV, PPIV and NZeelV. Background mortality was too high in the experiments performed at 22 degrees C for any conclusions about viral pathogenicity at this temperature to be drawn. Viruses could be re-isolated from samples from all challenged groups, and their presence in infected tissue was demonstrated using immunohistochemistry. The findings suggest that pike fry are susceptible to EHNV, ESV, PPIV and NZeelV and can be a vector for ECV and FV3. Statistical analysis of the factors associated with positive virus re-isolation showed that the number of fish in the sample influenced the outcome of virus re-isolation. Moreover, the likelihood of positive virus re-isolation significantly differed among the 6 viral isolates. The temperature from where the sample was taken and the number of days after infection were not associated with the probability of a positive virus re-isolation. PMID:19402450

  19. Mosquitoes as a Potential Vector of Ranavirus Transmission in Terrestrial Turtles.

    PubMed

    Kimble, Steven J A; Karna, Ajit K; Johnson, April J; Hoverman, Jason T; Williams, Rod N

    2014-09-12

    Ranaviruses are significant pathogens of amphibians, reptiles, and fishes, contributing to mass mortality events worldwide. Despite an increasing focus on ranavirus ecology, our understanding of ranavirus transmission, especially among reptilian hosts, remains limited. For example, experimental evidence for oral transmission of the virus in chelonians is mixed. Consequently, vector-borne transmission has been hypothesized in terrestrial turtle species. To test this hypothesis, mosquitoes captured during a 2012/2013 ranavirus outbreak in box turtles from southwestern Indiana were pooled by genus and tested for ranavirus DNA using qPCR. Two of 30 pools tested positive for ranavirus. Additionally, an individual Aedes sp. mosquito observed engorging on a box turtle also tested positive for ranavirus. Although our approach does not rule out the possibility that the sequenced ranavirus was simply from virus in bloodmeal, it does suggests that mosquitoes may be involved in virus transmission as a mechanical or biological vector among ectothermic vertebrates. While additional studies are needed to elucidate the exact role of mosquitoes in ranavirus ecology, our study suggests that a greater focus on vector-borne transmission may be necessary to fully understand ranaviral disease dynamics in herpetofauna. PMID:25212726

  20. Ranaviruses: Cold Blooded Killers!

    E-print Network

    Gray, Matthew

    similarity with the ranavirus FV3 Spp: n > 10P Blue Ridge 2-lined sylvaticus #12;3 Smoky Mountains Cades Cove: Gourley Pond Jamie Barichivich (USGS) and Megan Todd Cumberland Plateau TN River Ridge & Valley 40 Sites (and Bd) Hiwassee & Little Rivers 40+ Sites GSMNP Karen

  1. Comparing viral metagenomics methods using a highly multiplexed human viral pathogens reagent.

    PubMed

    Li, Linlin; Deng, Xutao; Mee, Edward T; Collot-Teixeira, Sophie; Anderson, Rob; Schepelmann, Silke; Minor, Philip D; Delwart, Eric

    2015-03-01

    Unbiased metagenomic sequencing holds significant potential as a diagnostic tool for the simultaneous detection of any previously genetically described viral nucleic acids in clinical samples. Viral genome sequences can also inform on likely phenotypes including drug susceptibility or neutralization serotypes. In this study, different variables of the laboratory methods often used to generate viral metagenomics libraries were compared for their abilities to detect multiple viruses and generate full genome coverage. A biological reagent consisting of 25 different human RNA and DNA viral pathogens was used to estimate the effect of filtration and nuclease digestion, DNA/RNA extraction methods, pre-amplification and the use of different library preparation kits on the detection of viral nucleic acids. Filtration and nuclease treatment led to slight decreases in the percentage of viral sequence reads and number of viruses detected. For nucleic acid extractions silica spin columns improved viral sequence recovery relative to magnetic beads and Trizol extraction. Pre-amplification using random RT-PCR while generating more viral sequence reads resulted in detection of fewer viruses, more overlapping sequences, and lower genome coverage. The ScriptSeq library preparation method retrieved more viruses and a greater fraction of their genomes than the TruSeq and Nextera methods. Viral metagenomics sequencing was able to simultaneously detect up to 22 different viruses in the biological reagent analyzed including all those detected by qPCR. Further optimization will be required for the detection of viruses in biologically more complex samples such as tissues, blood, or feces. PMID:25497414

  2. The Genome Sequence of the Emerging Common Midwife Toad Virus Identifies an Evolutionary Intermediate within Ranaviruses

    PubMed Central

    Mavian, Carla; López-Bueno, Alberto; Balseiro, Ana; Casais, Rosa; Alcamí, Antonio

    2012-01-01

    Worldwide amphibian population declines have been ascribed to global warming, increasing pollution levels, and other factors directly related to human activities. These factors may additionally be favoring the emergence of novel pathogens. In this report, we have determined the complete genome sequence of the emerging common midwife toad ranavirus (CMTV), which has caused fatal disease in several amphibian species across Europe. Phylogenetic and gene content analyses of the first complete genomic sequence from a ranavirus isolated in Europe show that CMTV is an amphibian-like ranavirus (ALRV). However, the CMTV genome structure is novel and represents an intermediate evolutionary stage between the two previously described ALRV groups. We find that CMTV clusters with several other ranaviruses isolated from different hosts and locations which might also be included in this novel ranavirus group. This work sheds light on the phylogenetic relationships within this complex group of emerging, disease-causing viruses. PMID:22301140

  3. Collapse of amphibian communities due to an introduced Ranavirus.

    PubMed

    Price, Stephen J; Garner, Trenton W J; Nichols, Richard A; Balloux, François; Ayres, César; Mora-Cabello de Alba, Amparo; Bosch, Jaime

    2014-11-01

    The emergence of infectious diseases with a broad host range can have a dramatic impact on entire communities and has become one of the main threats to biodiversity. Here, we report the simultaneous exploitation of entire communities of potential hosts with associated severe declines following invasion by a novel viral pathogen. We found two phylogenetically related, highly virulent viruses (genus Ranavirus, family Iridoviridae) causing mass mortality in multiple, diverse amphibian hosts in northern Spain, as well as a third, relatively avirulent virus. We document host declines in multiple species at multiple sites in the region. Our work reveals a group of pathogens that seem to have preexisting capacity to infect and evade immunity in multiple diverse and novel hosts, and that are exerting massive impacts on host communities. This report provides an exceptional record of host population trends being tracked in real time following emergence of a wildlife disease and a striking example of a novel, generalist pathogen repeatedly crossing the species barrier with catastrophic consequences at the level of host communities. PMID:25438946

  4. Amphibian chytrid fungus and ranaviruses in the Northwest Territories, Canada.

    PubMed

    Schock, Danna M; Ruthig, Gregory R; Collins, James P; Kutz, Susan J; Carrière, Suzanne; Gau, Robert J; Veitch, Alasdair M; Larter, Nicholas C; Tate, Douglas P; Guthrie, Glen; Allaire, Daniel G; Popko, Richard A

    2010-11-01

    Pathogens can cause serious declines in host species, and knowing where pathogens associated with host declines occur facilitates understanding host-pathogen ecology. Suspected drivers of global amphibian declines include infectious diseases, with 2 pathogens in particular, Batrachochytrium dendrobatidis (Bd) and ranaviruses, causing concern. We explored the host range and geographic distribution of Bd and ranaviruses in the Taiga Plains ecoregion of the Northwest Territories, Canada, in 2007 and 2008. Both pathogens were detected, greatly extending their known geographic distributions. Ranaviruses were widespread geographically, but found only in wood frogs. In contrast, Bd was found at a single site, but was detected in all 3 species of amphibians in the survey area (wood frogs, boreal chorus frogs, western toads). The presence of Bd in the Northwest Territories is not congruent with predicted distributions based on niche models, even though findings from other studies at northern latitudes are consistent with those same models. Unexpectedly, we also found evidence that swabs routinely used to collect samples for Bd screening detected fewer infections than toe clips. Our use and handling of the swabs was consistent with other studies, and the cause of the apparent lack of integrity of swabs is unknown. The ranaviruses detected in our study were confirmed to be Frog Virus 3 by sequence analysis of a diagnostic 500 bp region of the major capsid protein gene. It is unknown whether Bd or ranaviruses are recent arrivals to the Canadian north. However, the genetic analyses required to answer that question can inform larger debates about the origin of Bd in North America as well as the potential effects of climate change and industrial development on the distributions of these important amphibian pathogens. PMID:21268986

  5. Introduction of Ranavirus to Isolated Wood Frog Populations Could Cause Local Extinction.

    PubMed

    Earl, Julia E; Gray, Matthew J

    2014-06-25

    Amphibian declines and extinction have been attributed to many causes, including disease such as chytridiomycosis. Other pathogens may also contribute to declines, with ranavirus as the most likely candidate given reoccurring die-offs observed in the wild. We were interested in whether it is possible for ranavirus to cause extinction of a local, closed population of amphibians. We used susceptibility data from experimental challenges on different life stages combined with estimates of demographic parameters from a natural population to predict the likelihood of extinction using a stage-structured population model for wood frogs (Lithobates sylvaticus). Extinction was most likely when the larval or metamorph stage was exposed under frequent intervals in smaller populations. Extinction never occurred when only the egg stage was exposed to ranavirus. Under the worst-case scenario, extinction could occur in as quickly as 5 years with exposure every year and 25-44 years with exposure every 2 years. In natural wood frog populations, die-offs typically occur in the larval stage and can reoccur in subsequent years, indicating that our simulations represent possible scenarios. Additionally, wood frog populations are particularly sensitive to changes in survival during the pre-metamorphic stages when ranavirus tends to be most pathogenic. Our results suggest that ranavirus could contribute to amphibian species declines, especially for species that are very susceptible to ranavirus with closed populations. We recommend that ranavirus be considered in risk analyses for amphibian species. PMID:24962849

  6. Point detection of bacterial and viral pathogens using oral samples

    NASA Astrophysics Data System (ADS)

    Malamud, Daniel

    2008-04-01

    Oral samples, including saliva, offer an attractive alternative to serum or urine for diagnostic testing. This is particularly true for point-of-use detection systems. The various types of oral samples that have been reported in the literature are presented here along with the wide variety of analytes that have been measured in saliva and other oral samples. The paper focuses on utilizing point-detection of infectious disease agents, and presents work from our group on a rapid test for multiple bacterial and viral pathogens by monitoring a series of targets. It is thus possible in a single oral sample to identify multiple pathogens based on specific antigens, nucleic acids, and host antibodies to those pathogens. The value of such a technology for detecting agents of bioterrorism at remote sites is discussed.

  7. Infection Strategies of Bacterial and Viral Pathogens through Pathogen–Human Protein–Protein Interactions

    PubMed Central

    Durmu? Tekir, Saliha; Çakir, Tunahan; Ülgen, Kutlu Ö

    2012-01-01

    Since ancient times, even in today’s modern world, infectious diseases cause lots of people to die. Infectious organisms, pathogens, cause diseases by physical interactions with human proteins. A thorough analysis of these interspecies interactions is required to provide insights about infection strategies of pathogens. Here we analyzed the most comprehensive available pathogen–human protein interaction data including 23,435 interactions, targeting 5,210 human proteins. The data were obtained from the newly developed pathogen–host interaction search tool, PHISTO. This is the first comprehensive attempt to get a comparison between bacterial and viral infections. We investigated human proteins that are targeted by bacteria and viruses to provide an overview of common and special infection strategies used by these pathogen types. We observed that in the human protein interaction network the proteins targeted by pathogens have higher connectivity and betweenness centrality values than those proteins not interacting with pathogens. The preference of interacting with hub and bottleneck proteins is found to be a common infection strategy of all types of pathogens to manipulate essential mechanisms in human. Compared to bacteria, viruses tend to interact with human proteins of much higher connectivity and centrality values in the human network. Gene Ontology enrichment analysis of the human proteins targeted by pathogens indicates crucial clues about the infection mechanisms of bacteria and viruses. As the main infection strategy, bacteria interact with human proteins that function in immune response to disrupt human defense mechanisms. Indispensable viral strategy, on the other hand, is the manipulation of human cellular processes in order to use that transcriptional machinery for their own genetic material transcription. A novel observation about pathogen–human systems is that the human proteins targeted by both pathogens are enriched in the regulation of metabolic processes. PMID:22347880

  8. High susceptibility of the endangered dusky gopher frog to ranavirus.

    PubMed

    Sutton, William B; Gray, Matthew J; Hardman, Rebecca H; Wilkes, Rebecca P; Kouba, Andrew J; Miller, Debra L

    2014-11-14

    Amphibians are one of the most imperiled vertebrate groups, with pathogens playing a role in the decline of some species. Rare species are particularly vulnerable to extinction because populations are often isolated and exist at low abundance. The potential impact of pathogens on rare amphibian species has seldom been investigated. The dusky gopher frog Lithobates sevosus is one of the most endangered amphibian species in North America, with 100-200 individuals remaining in the wild. Our goal was to determine whether adult L. sevosus were susceptible to ranavirus, a pathogen responsible for amphibian die-offs worldwide. We tested the relative susceptibility of adult L. sevosus to ranavirus (103 plaque-forming units) isolated from a morbid bullfrog via 3 routes of exposure: intra-coelomic (IC) injection, oral (OR) inoculation, and water bath (WB) exposure. We observed 100% mortality of adult L. sevosus in the IC and WB treatments after 10 and 19 d, respectively. Ninety-five percent mortality occurred in the OR treatment over the 28 d evaluation period. No mortality was observed in the control treatment after 28 d. Our results indicate that L. sevosus is susceptible to ranavirus, and if adults in the wild are exposed to this pathogen, significant mortality could occur. Additionally, our study demonstrates that some adult amphibian species can be very susceptible to ranavirus, which has been often overlooked in North American studies. We recommend that conservation planners consider testing the susceptibility of rare amphibian species to ranavirus and that the adult age class is included in future challenge experiments. PMID:25392038

  9. Ranavirus: past, present and future

    PubMed Central

    Lesbarrères, D.; Balseiro, A.; Brunner, J.; Chinchar, V. G.; Duffus, A.; Kerby, J.; Miller, D. L.; Robert, J.; Schock, D. M.; Waltzek, T.; Gray, M. J.

    2012-01-01

    Emerging infectious diseases are a significant threat to global biodiversity. While historically overlooked, a group of iridoviruses in the genus Ranavirus has been responsible for die-offs in captive and wild amphibian, reptile and fish populations around the globe over the past two decades. In order to share contemporary information on ranaviruses and identify critical research directions, the First International Symposium on Ranaviruses was held in July 2011 in Minneapolis, MN, USA. Twenty-three scientists and veterinarians from nine countries examined the ecology and evolution of ranavirus–host interactions, potential reservoirs, transmission dynamics, as well as immunological and histopathological responses to infection. In addition, speakers discussed possible mechanisms for die-offs, and conservation strategies to control outbreaks. PMID:22048891

  10. De novo identification of viral pathogens from cell culture hologenomes

    PubMed Central

    2012-01-01

    Background Fast, specific identification and surveillance of pathogens is the cornerstone of any outbreak response system, especially in the case of emerging infectious diseases and viral epidemics. This process is generally tedious and time-consuming thus making it ineffective in traditional settings. The added complexity in these situations is the non-availability of pure isolates of pathogens as they are present as mixed genomes or hologenomes. Next-generation sequencing approaches offer an attractive solution in this scenario as it provides adequate depth of sequencing at fast and affordable costs, apart from making it possible to decipher complex interactions between genomes at a scale that was not possible before. The widespread application of next-generation sequencing in this field has been limited by the non-availability of an efficient computational pipeline to systematically analyze data to delineate pathogen genomes from mixed population of genomes or hologenomes. Findings We applied next-generation sequencing on a sample containing mixed population of genomes from an epidemic with appropriate processing and enrichment. The data was analyzed using an extensive computational pipeline involving mapping to reference genome sets and de-novo assembly. In depth analysis of the data generated revealed the presence of sequences corresponding to Japanese encephalitis virus. The genome of the virus was also independently de-novo assembled. The presence of the virus was in addition, verified using standard molecular biology techniques. Conclusions Our approach can accurately identify causative pathogens from cell culture hologenome samples containing mixed population of genomes and in principle can be applied to patient hologenome samples without any background information. This methodology could be widely applied to identify and isolate pathogen genomes and understand their genomic variability during outbreaks. PMID:22226071

  11. Quantitation of ranaviruses in cell culture and tissue samples.

    PubMed

    Holopainen, Riikka; Honkanen, Jarno; Jensen, Britt Bang; Ariel, Ellen; Tapiovaara, Hannele

    2011-01-01

    A quantitative real-time PCR (qPCR) based on a standard curve was developed for detection and quantitation of ranaviruses. The target gene for the qPCR was viral DNA polymerase (DNApol). All ten ranavirus isolates studied (Epizootic haematopoietic necrosis virus, EHNV; European catfish virus, ECV; European sheatfish virus, ESV; Frog virus 3, FV3; Bohle iridovirus, BIV; Doctor fish virus, DFV; Guppy virus 6, GV6; Pike-perch iridovirus, PPIV; Rana esculenta virus Italy 282/I02, REV282/I02 and Short-finned eel ranavirus, SERV) were detected with the qPCR assay. In addition, two fish cell lines - epithelioma papulosum cyprini (EPC) and bluegill fry (BF-2) - were infected with four of the isolates (EHNV, ECV, FV3 and DFV), and the viral quantity was determined from seven time points during the first three days after infection. The qPCR was also used to determine the viral load in tissue samples from pike (Esox lucius) fry challenged experimentally with EHNV. PMID:21087639

  12. 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

  13. The value of HIV protective epitope research for informed vaccine design against diverse viral pathogens

    PubMed Central

    Kramer, Victor G; Byrareddy, Siddappa N

    2014-01-01

    The success of vaccine regimens against viral pathogens hinges on the elicitation of protective responses. Hypervariable pathogens such as HIV avoid neutralization by masking protective epitopes with more immunogenic decoys. The identification of protective, conserved epitopes is crucial for future vaccine candidate design. The strategies employed for identification of HIV protective epitopes will also aid towards rational vaccine design for other viral pathogens. PMID:24964950

  14. Transmission of Ranavirus between Ectothermic Vertebrate Hosts

    E-print Network

    Gray, Matthew

    Transmission of Ranavirus between Ectothermic Vertebrate Hosts Roberto Brenes1 *, Matthew J. Gray2 ectothermic vertebrate hosts could explain the successful yearlong persistence of ranaviruses in aquatic was possible among three species from different ectothermic vertebrate classes: Cope's gray treefrog (Hyla

  15. First Evidence of Amphibian Chytrid Fungus (Batrachochytrium dendrobatidis) and Ranavirus in Hong Kong Amphibian Trade

    PubMed Central

    Kolby, Jonathan E.; Smith, Kristine M.; Berger, Lee; Karesh, William B; Preston, Asa; Pessier, Allan P.; Skerratt, Lee F.

    2014-01-01

    The emerging infectious amphibian diseases caused by amphibian chytrid fungus (Batrachochytrium dendrobatidis, Bd) and ranaviruses are responsible for global amphibian population declines and extinctions. Although likely to have been spread by a variety of activities, transcontinental dispersal appears closely associated with the international trade in live amphibians. The territory of Hong Kong reports frequent, high volume trade in amphibians, and yet the presence of Bd and ranavirus have not previously been detected in either traded or free-ranging amphibians. In 2012, a prospective surveillance project was conducted to investigate the presence of these pathogens in commercial shipments of live amphibians exported from Hong Kong International Airport. Analysis of skin (Bd) and cloacal (ranavirus) swabs by quantitative PCR detected pathogen presence in 31/265 (11.7%) and in 105/185 (56.8%) of amphibians, respectively. In addition, the water in which animals were transported tested positive for Bd, demonstrating the risk of pathogen pollution by the disposal of untreated wastewater. It is uncertain whether Bd and ranavirus remain contained within Hong Kong’s trade sector, or if native amphibians have already been exposed. Rapid response efforts are now urgently needed to determine current pathogen distribution in Hong Kong, evaluate potential trade-associated exposure to free-ranging amphibians, and identify opportunities to prevent disease establishment. PMID:24599268

  16. New approaches to the inhibition of replication of viral pathogens.

    PubMed

    Kumar, Anil; Silverstein, Peter S

    2011-11-01

    This meeting was a special symposium sponsored by the American Society for Biochemistry and Molecular Biology. The conference was held in Gangzhou, China on 24-26 July 2011 and shared a venue with the Society of Chinese Bioscientists in America Thirteenth International Symposium. Over 150 participants from the Americas, Europe, Asia and Australia attended the meeting. This article focuses on two areas of research in which there have been exciting developments that have application to the development of antivirals: the regulation of host and viral mRNA by RNAi and NF-?B regulation of viral gene expression. PMID:22029515

  17. DEVELOPMENT OF BIOMARKER OF EXPOSURE TO VIRAL PATHOGENS

    EPA Science Inventory

    Interferon gamma (IFN-?) was selected as a biomarker for a viral exposure study. Twelve-week-old BALB/c mice were intraperitoneally injected with 0.2ml of 104 PFU/ml of coxsackievirus B3 or B4 diluted in phosphate-buffered saline (PBS). Control mice were injected with PBS on...

  18. Reliability of non-lethal surveillance methods for detecting ranavirus infection.

    PubMed

    Gray, Matthew J; Miller, Debra L; Hoverman, Jason T

    2012-05-15

    Ranaviruses have been identified as the etiologic agent in many amphibian die-offs across the globe. Polymerase chain reaction (PCR) is commonly used to detect ranavirus infection in amphibian hosts, but the test results may vary between tissue samples obtained by lethal and non-lethal procedures. Testing liver samples for infection is a common lethal sampling technique to estimate ranavirus prevalence because the pathogen often targets this organ and the liver is easy to identify and collect. However, tail clips or swabs may be more practicable for ranavirus surveillance programs compared with collecting and euthanizing animals, especially for uncommon species. Using PCR results from liver samples for comparison, we defined false-positive test results as occurrences when a non-lethal technique indicated positive but the liver sample was negative. Similarly, we defined false-negative test results as occurrences when a non-lethal technique was negative but the liver sample was positive. Using these decision rules, we estimated false-negative and false-positive rates for tail clips and swabs. Our study was conducted in a controlled facility using American bullfrog Lithobates catesbeianus tadpoles; false-positive and false-negative rates were estimated after different periods of time following exposure to ranavirus. False-negative and false-positive rates were 20 and 6%, respectively, for tail samples, and 22 and 12%, respectively, for swabs. False-negative rates were constant over time, but false-positive rates decreased with post-exposure duration. Our results suggest that non-lethal sampling techniques can be useful for ranavirus surveillance, although the prevalence of infection may be underestimated when compared to results obtained with liver samples. PMID:22585297

  19. Susceptibility of fish and turtles to three ranaviruses isolated from different ectothermic vertebrate classes.

    PubMed

    Brenes, Roberto; Miller, Debra L; Waltzek, Thomas B; Wilkes, Rebecca P; Tucker, Jennifer L; Chaney, Jordan C; Hardman, Rebecca H; Brand, Mabre D; Huether, Rebecca R; Gray, Matthew J

    2014-06-01

    Ranaviruses have been associated with mortality of lower vertebrates around the world. Frog virus 3 (FV3)-like ranaviruses have been isolated from different ectothermic vertebrate classes; however, few studies have demonstrated whether this pathogen can be transmitted among classes. Using FV3-like ranaviruses isolated from the American bullfrog Lithobates catesbeianus, eastern box turtle Terrapene carolina carolina, and Pallid Sturgeon Scaphirhynchus albus, we tested for the occurrence of interclass transmission (i.e., infection) and host susceptibility (i.e., percent mortality) for five juvenile fish and three juvenile turtle species exposed to each of these isolates. Exposure was administered via water bath (10(3) PFU/mL) for 3 d and survival was monitored for 28 d. Florida softshell turtles Apalone ferox experienced no mortality, but 10% and 20% of individuals became infected by the turtle and fish isolate, respectively. Similarly, 5% of Mississippi map turtles Graptemys pseudogeographica kohni were subclinically infected with the turtle isolate at the end of the experiment. Channel Catfish Ictalurus punctatus experienced 5% mortality when exposed to the turtle isolate, while Western Mosquitofish Gambusia affinis experienced 10% mortality when exposed to the turtle and amphibian isolates and 5% mortality when exposed to the fish isolate. Our results demonstrated that interclass transmission of FV3-like ranaviruses is possible. Although substantial mortality did not occur in our experiments, the occurrence of low mortality and subclinical infections suggest that fish and aquatic turtles may function as reservoirs for FV3-like ranaviruses. Additionally, our study is the first to report transmission of FV3-like ranaviruses between fish and chelonians. PMID:24895866

  20. Detection of viral pathogens in high grade gliomas from unmapped next-generation sequencing data.

    PubMed

    Cimino, Patrick J; Zhao, Guoyan; Wang, David; Sehn, Jennifer K; Lewis, James S; Duncavage, Eric J

    2014-06-01

    Viral pathogens have been implicated in the development of certain cancers including human papillomavirus (HPV) in squamous cell carcinoma and Epstein-Barr virus (EBV) in Burkitt's lymphoma. The significance of viral pathogens in brain tumors is controversial, and human cytomegalovirus (HCMV) has been associated with glioblastoma (GBM) in some but not all studies, making the role of HCMV unclear. In this study we sought to determine if viral pathogen sequences could be identified in an unbiased manner from previously discarded, unmapped, non-human, next-generation sequencing (NGS) reads obtained from targeted oncology, panel-based sequencing of high grade gliomas (HGGs), including GBMs. Twenty one sequential HGG cases were analyzed by a targeted NGS clinical oncology panel containing 151 genes using DNA obtained from formalin-fixed, paraffin-embedded (FFPE) tissue. Sequencing reads that did not map to the human genome (average of 38,000 non-human reads/case (1.9%)) were filtered and low quality reads removed. Extracted high quality reads were then sequentially aligned to the National Center for Biotechnology Information (NCBI) non-redundant nucleotide (nt and nr) databases. Aligned reads were classified based on NCBI taxonomy database and all eukaryotic viral sequences were further classified into viral families. Two viral sequences (both herpesviruses), EBV and Roseolovirus were detected in 5/21 (24%) cases and in 1/21 (5%) cases, respectively. None of the cases had detectable HCMV. Of the five HGG cases with detectable EBV DNA, four had additional material for EBV in situ hybridization (ISH), all of which were negative for expressed viral sequence. Overall, a similar discovery approach using unmapped non-human NGS reads could be used to discover viral sequences in other cancer types. PMID:24704430

  1. VIRAL PATHOGENS AND MICROBIOLOGICAL INDICATORS IN GROUND WATER FROM SMALL PUBLIC WATER SUPPLIES IN SOUTHEASTERN MICHIGAN

    EPA Science Inventory

    Thirty-eight public ground-water-supply wells serving less than 3,300 people were sampled from July 1999 through July 2001 in southeastern Michigan to determine (1) occurrence of viral pathogens and microbiological indicators, (2) whether indicators are adequate predictors of the...

  2. First molecular detection of a viral pathogen in Ugandan honey bees

    Microsoft Academic Search

    Robert Kajobe; Gay Marris; Giles Budge; Lynn Laurenson; Guido Cordoni; Ben Jones; Selwyn Wilkins; Andrew G. S. Cuthbertson; Mike A. Brown

    2010-01-01

    Ugandan honey bees (Apis mellifera L.) produce honey, and are key pollinators within commercial crops and natural ecosystems. Real-time RT-PCR was used to screen immature and adult bees collected from 63 beekeeping sites across Uganda for seven viral pathogens. No samples tested positive for Chronic bee paralysis virus, Sacbrood virus, Deformed wing virus, Acute bee paralysis virus, Apis iridescent virus

  3. MULTIPLEXED IMMUNOASSAYS FOR VIRAL PATHOGENS UTILIZING SURFACE-ENHANCED RAMAN SCATTERING

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A sandwich immunoassay for the selective detection of viral pathogens has been developed using surface-enhanced Raman scattering (SERS) as the readout technology. The strengths of SERS-based detection include ultrahigh sensitivity and the possibility of multiplexing using multiple tags. The viabilit...

  4. A review on viral biosensors to detect human pathogens.

    PubMed

    Caygill, Rebecca L; Blair, G Eric; Millner, Paul A

    2010-11-29

    Rapid identification of viruses has important implications for medical healthcare. Current methods for identification and quantification of particular virus are time consuming and often expensive. Therefore, demand for sensitive and accurate viral biosensors with rapid detection systems is increasing. A hand held biosensing device would give fast, reliable results for identifying and quantitating the number of virus particles in a sample. Techniques currently being applied to achieve this aim include electrochemical biosensors, based on amperometric, potentiometric and impedance measurement, optical biosensors using surface plasmon resonance (SPR), optical fibers and piezoelectric biosensors based on microcantilevers. Future research also looks to the use of nanoparticles and novel nanomaterials as alternate recognition surfaces for use in a variety of sensor formats. PMID:21035597

  5. Rapid Accurate Identification of Bacterial and Viral Pathogens

    SciTech Connect

    Dunn, John

    2007-03-09

    The goals of this program were to develop two assays for rapid, accurate identification of pathogenic organisms at the strain level. The first assay "Quantitative Genome Profiling or QGP" is a real time PCR assay with a restriction enzyme-based component. Its underlying concept is that certain enzymes should cleave genomic DNA at many sites and that in some cases these cuts will interrupt the connection on the genomic DNA between flanking PCR primer pairs thereby eliminating selected PCR amplifications. When this occurs the appearance of the real-time PCR threshold (Ct) signal during DNA amplification is totally eliminated or, if cutting is incomplete, greatly delayed compared to an uncut control. This temporal difference in appearance of the Ct signal relative to undigested control DNA provides a rapid, high-throughput approach for DNA-based identification of different but closely related pathogens depending upon the nucleotide sequence of the target region. The second assay we developed uses the nucleotide sequence of pairs of shmi identifier tags (-21 bp) to identify DNA molecules. Subtle differences in linked tag pair combinations can also be used to distinguish between closely related isolates..

  6. Structural basis of glycan interaction in gastroenteric viral pathogens

    PubMed Central

    Prasad, B.V. Venkataram; Shanker, Sreejesh; Hu, Liya; Choi, Jae-Mun; Crawford, Sue E; Ramani, Sasirekha; Czako, Rita; Atmar, Robert L; Estes, Mary K

    2014-01-01

    A critical event in the life cycle of a virus is its initial attachment to host cells. This involves recognition by the viruses of specific receptors on the cell surface, including glycans. Viruses typically exhibit strain-dependent variations in recognizing specific glycan receptors, a feature that contributes significantly to cell tropism, host specificity, host adaptation and interspecies transmission. Examples include influenza viruses, noroviruses, rotaviruses, and parvoviruses. Both rotaviruses and noroviruses are well known gastroenteric pathogens that are of significant global health concern. While rotaviruses, in the family Reoviridae, are the major causative agents of life-threatening diarrhea in children, noroviruses, which belong to Caliciviridae family, cause epidemic and sporadic cases of acute gastroenteritis across all age groups. Both exhibit enormous genotypic and serotypic diversity. Consistent with this diversity each exhibits strain-dependent variations in the types of glycans they recognize for cell attachment. This chapter reviews current status of the structural biology of such strain-dependent glycan specificities in these two families of viruses. PMID:25073118

  7. Recognition of the Hyaloperonospora parasitica effector ATR13 triggers resistance against oomycete, bacterial, and viral pathogens.

    PubMed

    Rentel, Maike C; Leonelli, Lauriebeth; Dahlbeck, Douglas; Zhao, Bingyu; Staskawicz, Brian J

    2008-01-22

    Phytopathogenic oomycetes cause some of the most devastating diseases affecting agricultural crops. Hyaloperonospora parasitica is a native oomycete pathogen of Arabidopsis and is related to other oomycete phytopathogens that include several species of Phytophthora, including the causal agent of potato late blight. Recently, four oomycete effector genes have been isolated, and several oomycete genomes have been sequenced. We have developed an efficient and genetically amenable system to test putative effector genes using the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. The H. parasitica effector protein ATR13 was delivered via P. syringae by fusing the ATR13 gene with the avrRpm1 type three secretion signal peptide, a bacterial sequence that allows transfer of proteins into the host cell through the bacterial type III secretion system. We also inserted ATR13 into the genome of the turnip mosaic virus, a single-stranded RNA virus. Our results show that delivery of ATR13 via the bacterial or viral pathogen triggers defense responses in plants containing the cognate resistance protein RPP13(Nd), which restricts proliferation of both pathogens. Hence, recognition of ATR13 by RPP13 initiates defense responses that are effective against oomycete, bacterial and viral pathogens, pointing to a common defense mechanism. We have characterized regions of the RPP13(Nd) resistance protein that are essential for effector recognition and/or downstream signaling, using transient coexpression in Nicotiana benthamiana. PMID:18198274

  8. Recognition of the Hyaloperonospora parasitica effector ATR13 triggers resistance against oomycete, bacterial, and viral pathogens

    PubMed Central

    Rentel, Maike C.; Leonelli, Lauriebeth; Dahlbeck, Douglas; Zhao, Bingyu; Staskawicz, Brian J.

    2008-01-01

    Phytopathogenic oomycetes cause some of the most devastating diseases affecting agricultural crops. Hyaloperonospora parasitica is a native oomycete pathogen of Arabidopsis and is related to other oomycete phytopathogens that include several species of Phytophthora, including the causal agent of potato late blight. Recently, four oomycete effector genes have been isolated, and several oomycete genomes have been sequenced. We have developed an efficient and genetically amenable system to test putative effector genes using the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. The H. parasitica effector protein ATR13 was delivered via P. syringae by fusing the ATR13 gene with the avrRpm1 type three secretion signal peptide, a bacterial sequence that allows transfer of proteins into the host cell through the bacterial type III secretion system. We also inserted ATR13 into the genome of the turnip mosaic virus, a single-stranded RNA virus. Our results show that delivery of ATR13 via the bacterial or viral pathogen triggers defense responses in plants containing the cognate resistance protein RPP13Nd, which restricts proliferation of both pathogens. Hence, recognition of ATR13 by RPP13 initiates defense responses that are effective against oomycete, bacterial and viral pathogens, pointing to a common defense mechanism. We have characterized regions of the RPP13Nd resistance protein that are essential for effector recognition and/or downstream signaling, using transient coexpression in Nicotiana benthamiana. PMID:18198274

  9. Torque teno virus: an improved indicator for viral pathogens in drinking waters

    PubMed Central

    Griffin, Jennifer S; Plummer, Jeanine D; Long, Sharon C

    2008-01-01

    Background Currently applied indicator organism systems, such as coliforms, are not fully protective of public health from enteric viruses in water sources. Waterborne disease outbreaks have occurred in systems that tested negative for coliforms, and positive coliform results do not necessarily correlate with viral risk. It is widely recognized that bacterial indicators do not co-occur exclusively with infectious viruses, nor do they respond in the same manner to environmental or engineered stressors. Thus, a more appropriate indicator of health risks from infectious enteric viruses is needed. Presentation of the hypothesis Torque teno virus is a small, non-enveloped DNA virus that likely exhibits similar transport characteristics to pathogenic enteric viruses. Torque teno virus is unique among enteric viral pathogens in that it appears to be ubiquitous in humans, elicits seemingly innocuous infections, and does not exhibit seasonal fluctuations or epidemic spikes. Torque teno virus is transmitted primarily via the fecal-oral route and can be assayed using rapid molecular techniques. We hypothesize that Torque teno virus is a more appropriate indicator of viral pathogens in drinking waters than currently used indicator systems based solely on bacteria. Testing the hypothesis To test the hypothesis, a multi-phased research approach is needed. First, a reliable Torque teno virus assay must be developed. A rapid, sensitive, and specific PCR method using established nested primer sets would be most appropriate for routine monitoring of waters. Because PCR detects both infectious and inactivated virus, an in vitro method to assess infectivity also is needed. The density and occurrence of Torque teno virus in feces, wastewater, and source waters must be established to define spatial and temporal stability of this potential indicator. Finally, Torque teno virus behavior through drinking water treatment plants must be determined with co-assessment of traditional indicators and enteric viral pathogens to assess whether correlations exist. Implications of the hypothesis If substantiated, Torque teno virus could provide a completely new, reliable, and efficient indicator system for viral pathogen risk. This indicator would have broad application to drinking water utilities, watershed managers, and protection agencies and would provide a better means to assess viral risk and protect public health. PMID:18834517

  10. Catalog of Micro-Tom tomato responses to common fungal, bacterial, and viral pathogens

    Microsoft Academic Search

    Hideki Takahashi; Ayano Shimizu; Tsutomu Arie; Syofi Rosmalawati; Sumire Fukushima; Mari Kikuchi; Yasufumi Hikichi; Ayami Kanda; Akiko Takahashi; Akinori Kiba; Kohei Ohnishi; Yuki Ichinose; Fumiko Taguchi; Chihiro Yasuda; Motoichiro Kodama; Mayumi Egusa; Chikara Masuta; Hiroyuki Sawada; Daisuke Shibata; Koichi Hori; Yuichiro Watanabe

    2005-01-01

    Lycopersicon esculentum cultivar Micro-Tom is a miniature tomato with many advantages for studies of the molecular biology and physiology of plants. To evaluate the suitability of Micro-Tom as a host plant for the study of pathogenesis, Micro-Tom plants were inoculated with 16 well-known fungal, bacterial, and viral pathogens of tomato. Athelia rolfsii, Botryotinia fuckeliana, Oidium sp., Phytophthora infestans, and Sclerotinia

  11. Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination

    PubMed Central

    Thissen, James B.; Gardner, Shea N.; McLoughlin, Kevin S.; Glausser, Margaret K.; Jaing, Crystal J.

    2014-01-01

    In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV). Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA), was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR) was conducted. The LLMDA technology was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae, Bacteroidaceae, and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations. PMID:24778651

  12. Screening of viral pathogens from pediatric ileal tissue samples after vaccination.

    PubMed

    Hewitson, Laura; Thissen, James B; Gardner, Shea N; McLoughlin, Kevin S; Glausser, Margaret K; Jaing, Crystal J

    2014-01-01

    In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV). Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA), was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR) was conducted. The LLMDA technology was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15-62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae, Bacteroidaceae, and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations. PMID:24778651

  13. A unified method to process biosolids samples for the recovery of bacterial, viral, and helminths pathogens.

    PubMed

    Alum, Absar; Rock, Channah; Abbaszadegan, Morteza

    2014-01-01

    For land application, biosolids are classified as Class A or Class B based on the levels of bacterial, viral, and helminths pathogens in residual biosolids. The current EPA methods for the detection of these groups of pathogens in biosolids include discrete steps. Therefore, a separate sample is processed independently to quantify the number of each group of the pathogens in biosolids. The aim of the study was to develop a unified method for simultaneous processing of a single biosolids sample to recover bacterial, viral, and helminths pathogens. At the first stage for developing a simultaneous method, nine eluents were compared for their efficiency to recover viruses from a 100 gm spiked biosolids sample. In the second stage, the three top performing eluents were thoroughly evaluated for the recovery of bacteria, viruses, and helminthes. For all three groups of pathogens, the glycine-based eluent provided higher recovery than the beef extract-based eluent. Additional experiments were performed to optimize performance of glycine-based eluent under various procedural factors such as, solids to eluent ratio, stir time, and centrifugation conditions. Last, the new method was directly compared with the EPA methods for the recovery of the three groups of pathogens spiked in duplicate samples of biosolids collected from different sources. For viruses, the new method yielded up to 10% higher recoveries than the EPA method. For bacteria and helminths, recoveries were 74% and 83% by the new method compared to 34% and 68% by the EPA method, respectively. The unified sample processing method significantly reduces the time required for processing biosolids samples for different groups of pathogens; it is less impacted by the intrinsic variability of samples, while providing higher yields (P = 0.05) and greater consistency than the current EPA methods. PMID:24521413

  14. Identification of Viral Pathogen Diversity in Sewage Sludge by Metagenome Analysis

    PubMed Central

    BIBBY, KYLE; PECCIA, JORDAN

    2013-01-01

    The large diversity of viruses that exist in human populations are potentially excreted into sewage collection systems and concentrated in sewage sludge. In the US, the primary fate of processed sewage sludge (class B biosolids) is application to agricultural land as a soil amendment. To characterize and understand infectious risks associated with land application, and to describe the diversity of viruses in human populations, shotgun viral metagenomics was applied to 10 sewage sludge samples from 5 wastewater treatment plants throughout the continental U.S, each serving between 100,000 and 1,000,000 people. Nearly 330 million DNA sequences were produced and assembled, and annotation resulted in identifying 43 (26 DNA, 17 RNA) different types of human viruses in sewage sludge. Novel insights include the high abundance of newly emerging viruses (e.g. Coronavirus HKU1, Klassevirus, and Cosavirus) the strong representation of respiratory viruses, and the relatively minor abundance and occurrence of Enteroviruses. Viral metagenome sequence annotations were reproducible and independent PCR-based identification of selected viruses suggests that viral metagenomes were a conservative estimate of the true viral occurrence and diversity. These results represent the most complete description of human virus diversity in any wastewater sample to date, provide engineers and environmental scientists with critical information on important viral agents and routes of infection from exposure to wastewater and sewage sludge, and represent a significant leap forward in understanding the pathogen content of class B biosolids. PMID:23346855

  15. RNA Viral Community in Human Feces: Prevalence of Plant Pathogenic Viruses

    PubMed Central

    Lee, Wah Heng; Run, Jin-Quan; Wei, Chia Lin; Soh, Shirlena Wee Ling; Hibberd, Martin L; Liu, Edison T; Rohwer, Forest

    2006-01-01

    The human gut is known to be a reservoir of a wide variety of microbes, including viruses. Many RNA viruses are known to be associated with gastroenteritis; however, the enteric RNA viral community present in healthy humans has not been described. Here, we present a comparative metagenomic analysis of the RNA viruses found in three fecal samples from two healthy human individuals. For this study, uncultured viruses were concentrated by tangential flow filtration, and viral RNA was extracted and cloned into shotgun viral cDNA libraries for sequencing analysis. The vast majority of the 36,769 viral sequences obtained were similar to plant pathogenic RNA viruses. The most abundant fecal virus in this study was pepper mild mottle virus (PMMV), which was found in high concentrations—up to 109 virions per gram of dry weight fecal matter. PMMV was also detected in 12 (66.7%) of 18 fecal samples collected from healthy individuals on two continents, indicating that this plant virus is prevalent in the human population. A number of pepper-based foods tested positive for PMMV, suggesting dietary origins for this virus. Intriguingly, the fecal PMMV was infectious to host plants, suggesting that humans might act as a vehicle for the dissemination of certain plant viruses. PMID:16336043

  16. Herpetological First Report of Ranavirus Infecting Lungless

    E-print Network

    Gray, Matthew

    * DEBRA L. MILLER** and JASON T. HOVERMAN Center for Wildlife Health, Department of Forestry, Wildlife Report of Ranavirus Infecting Lungless Salamanders MATTHEW J. GRAY* DEBRA L. MILLER** and JASON T (Picco and Collins 2008) or increased occurrence of anthropogenic stressors on the landscape (Forson

  17. Serological survey of viral pathogens in bean and white-fronted geese from Germany.

    PubMed

    Hlinak, A; Müller, T; Kramer, M; Mühle, R U; Liebherr, H; Ziedler, K

    1998-07-01

    Sera from wild geese were tested for antibodies to selected viral pathogens at a resting site for wild waterfowl in Germany. Serum samples from both bean geese (Anser fabalis) and white-fronted geese (Anser albifrons) collected in October 1991 were examined using serological methods licensed for routine diagnosis in domestic poultry. Of 130 sera tested, antibodies to several infectious agents were found including Newcastle disease virus (45%), goose parvovirus (48%), avian reovirus (29%), and avian adenovirus or egg drop syndrome 76 virus (6%). Antibodies against duck hepatitis virus were not detected. Differences in seroprevalences were not detected between the two geese species. While role and significance of wild geese in the epidemiology of avian diseases remains to be determined, it is possible that they could be of some importance as reservoirs and carriers of certain viral diseases of domestic poultry. PMID:9706557

  18. Comparison of four multiplex PCR assays for the detection of viral pathogens in respiratory specimens.

    PubMed

    Anderson, Trevor P; Werno, Anja M; Barratt, Kevin; Mahagamasekera, Patalee; Murdoch, David R; Jennings, Lance C

    2013-08-01

    Multiplex PCR has become the test of choice for the detection of multiple respiratory viruses in clinical specimens. However, there are few direct comparisons of different PCR assays. This study compares 4 different multiplex PCR assays for the recovery of common respiratory viruses. We tested 213 respiratory specimens using four different multiplex PCR assays: the xTAG respiratory viral panel fast (Abbott Molecular Laboratories), Fast-track Respiratory Pathogen assay (Fast-track Diagnostics), Easyplex respiratory pathogen 12 kit (Ausdiagnostics), and an in-house multiplex real-time PCR assay. The performance of the four assays was very similar, with 93-100% agreement for all comparisons. Other issues, such as through-put, technical requirements and cost, are likely to be as important for making a decision about which of these assays to use given their comparative performance. PMID:23583489

  19. Susceptibility of black bullhead Ameiurus melas to a panel of ranavirus isolates.

    PubMed

    Gobbo, F; Cappellozza, E; Pastore, M R; Bovo, G

    2010-07-01

    Ranaviruses are considered a serious threat to lower vertebrates, including fish, amphibians and reptiles. However, epidemiological data on these agents are lacking, and further investigations are needed to understand the role of carriers and to update the list of susceptible hosts. We carried out various experimental infections under controlled conditions to contribute to the current knowledge on the susceptibility of black bullhead Ameiurus melas to European catfish virus (ECV) and other ranaviruses. A panel of 7 ranavirus isolates was used to challenge duplicate groups of A. melas juveniles maintained in aquaria supplied with running dechlorinated tap water. The experiments were performed at 15 and 25 degrees C. The results confirmed the high susceptibility of A. melas to ECV infection. Furthermore, a significant mortality associated with the typical signs of systemic viral infections was observed in groups challenged with Epizootic haematopoietic necrosis virus (EHNV) at 25 degrees C, and to a lesser extent, at 15 degrees C. No significant mortality was recorded in fish challenged with European sheatfish virus (ESV), Frog virus 3 (FV3), Rana esculenta virus-like (REV-like), Bohle iridovirus (BIV) or short-finned eel virus (SERV). PMID:20815324

  20. Development and Disease: How Susceptibility to an Emerging Pathogen Changes through Anuran Development

    PubMed Central

    Haislip, Nathan A.; Gray, Matthew J.; Hoverman, Jason T.; Miller, Debra L.

    2011-01-01

    Ranaviruses have caused die-offs of amphibians across the globe. In North America, these pathogens cause more amphibian mortality events than any other pathogen. Field observations suggest that ranavirus epizootics in amphibian communities are common during metamorphosis, presumably due to changes in immune function. However, few controlled studies have compared the relative susceptibility of amphibians to ranaviruses across life stages. Our objectives were to measure differences in mortality and infection prevalence following exposure to ranavirus at four developmental stages and determine whether the differences were consistent among seven anuran species. Based on previous studies, we hypothesized that susceptibility to ranavirus would be greatest at metamorphosis. Our results did not support this hypothesis, as four of the species were most susceptible to ranavirus during the larval or hatchling stages. The embryo stage had the lowest susceptibility among species probably due to the protective membranous layers of the egg. Our results indicate that generalizations should be made cautiously about patterns of susceptibility to ranaviruses among amphibian developmental stages and species. Further, if early developmental stages of amphibians are susceptible to ranaviruses, the impact of ranavirus epizootic events may be greater than realized due to the greater difficulty of detecting morbid hatchlings and larvae compared to metamorphs. PMID:21799820

  1. Extended Viral Shedding of a Low Pathogenic Avian Influenza Virus by Striped Skunks (Mephitis mephitis)

    PubMed Central

    Root, J. Jeffrey; Shriner, Susan A.; Bentler, Kevin T.; Gidlewski, Thomas; Mooers, Nicole L.; Ellis, Jeremy W.; Spraker, Terry R.; VanDalen, Kaci K.; Sullivan, Heather J.; Franklin, Alan B.

    2014-01-01

    Background Striped skunks (Mephitis mephitis) are susceptible to infection with some influenza A viruses. However, the viral shedding capability of this peri-domestic mammal and its potential role in influenza A virus ecology are largely undetermined. Methodology/Principal Findings Striped skunks were experimentally infected with a low pathogenic (LP) H4N6 avian influenza virus (AIV) and monitored for 20 days post infection (DPI). All of the skunks exposed to H4N6 AIV shed large quantities of viral RNA, as detected by real-time RT-PCR and confirmed for live virus with virus isolation, from nasal washes and oral swabs (maximum ?106.02 PCR EID50 equivalent/mL and ?105.19 PCR EID50 equivalent/mL, respectively). Some evidence of potential fecal shedding was also noted. Following necropsy on 20 DPI, viral RNA was detected in the nasal turbinates of one individual. All treatment animals yielded evidence of a serological response by 20 DPI. Conclusions/Significance These results indicate that striped skunks have the potential to shed large quantities of viral RNA through the oral and nasal routes following exposure to a LP AIV. Considering the peri-domestic nature of these animals, along with the duration of shedding observed in this species, their presence on poultry and waterfowl operations could influence influenza A virus epidemiology. For example, this species could introduce a virus to a naive poultry flock or act as a trafficking mechanism of AIV to and from an infected poultry flock to naive flocks or wild bird populations. PMID:24489638

  2. Impacts of Stressors on Ranavirus Prevalence in American Bullfrog and

    E-print Network

    Gray, Matthew

    Failure (necrosis or apoptosis) Emergence of Ranavirus Anthropogenic Stressor Hypothesis Decrease Water stages Water Temperature & Development Study Area and Tadpole Sampling Plateau Research and Education Homogenate: liver, spleen, kidney, heart, gills and lungs ·Histology Electrophoresis of Ranavirus PCR 100

  3. Inflammation-Induced Reactivation of the Ranavirus Frog Virus 3 in Asymptomatic Xenopus laevis

    PubMed Central

    Robert, Jacques; Grayfer, Leon; Edholm, Eva-Stina; Ward, Brian; De Jesús Andino, Francisco

    2014-01-01

    Natural infections of ectothermic vertebrates by ranaviruses (RV, family Iridoviridae) are rapidly increasing, with an alarming expansion of RV tropism and resulting die-offs of numerous animal populations. Notably, infection studies of the amphibian Xenopus laevis with the ranavirus Frog Virus 3 (FV3) have revealed that although the adult frog immune system is efficient at controlling RV infections, residual quiescent virus can be detected in mononuclear phagocytes of otherwise asymptomatic animals following the resolution of RV infections. It is noteworthy that macrophage-lineage cells are now believed to be a critical element in the RV infection strategy. In the present work, we report that inflammation induced by peritoneal injection of heat-killed bacteria in asymptomatic frogs one month after infection with FV3 resulted in viral reactivation including detectable viral DNA and viral gene expression in otherwise asymptomatic frogs. FV3 reactivation was most prominently detected in kidneys and in peritoneal HAM56+ mononuclear phagocytes. Notably, unlike adult frogs that typically clear primary FV3 infections, a proportion of the animals succumbed to the reactivated FV3 infection, indicating that previous exposure does not provide protection against subsequent reactivation in these animals. PMID:25390636

  4. A Decrease in Albumin in Early SIV Infection Is Related to Viral Pathogenicity

    PubMed Central

    Holte, Sarah; Kimata, Jason T.; Wener, Mark H.; Overbaugh, Julie

    2009-01-01

    Abstract A decrease in circulating albumin levels after seroconversion has been reported as a predictor of disease progression in HIV-infected adults. We hypothesized that a similar decrease would be seen in pig-tailed macaques in early SIV infection, and that the degree of this decrease would be related to the pathogenicity of the infecting viral strain. Ten juvenile pig-tailed macaques were previously inoculated with virus derived from molecular clones representing different stages of infection: early (SIVMneCL8, n?=?2), intermediate (SIVMne35wkSU, n?=?2), late blood (SIVMne170, n?=?3), or late lymph node (SIVMne027, n?=?3). Albumin was measured in stored samples. Changes from baseline were evaluated by paired sample t tests and by linear regression with generalized estimating equations (GEE). Albumin levels decreased in the week after SIV inoculation (p?=?0.02), increased above baseline at week 5, then fell, returning below baseline by week 16 (p?=?0.03). In GEE modeling, albumin decreased significantly in both early and chronic infection (weeks 0–3, p?pathogenic virus variants. These results suggest that both early and late events in SIV pathogenesis are influenced by properties of the infecting viral strain. PMID:19320603

  5. DIFFERENCES IN PATHOGENICITY AND VIRAL GENOME BETWEEN COXSACKIEVIRUS B3/0 PASSED THROUGH YOUNG VERSUS OLD MICE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously we have observed that amyocarditic coxsackievirus (CVB3/0) becomes virulent and pathogenic after passage through an aged host due to specific changes in the viral genome. To demonstrate that this effect was specific to the old host environment and not due to passage through a host in gene...

  6. Respiratory viral pathogens among Singapore military servicemen 2009 – 2012: epidemiology and clinical characteristics

    PubMed Central

    2014-01-01

    Background Few studies have comprehensively described tropical respiratory disease surveillance in military populations. There is also a lack of studies comparing clinical characteristics of the non-influenza pathogens with influenza and amongst themselves. Methods From May 2009 through October 2012, 7733 consenting cases of febrile respiratory illness (FRI) (temperature [greater than or equal to]37.5degreesC with cough or sorethroat) and controls in the Singapore military had clinical data and nasal washes collected prospectively. Nasal washes underwent multiplex PCR, and the analysis was limited to viral mono-infections. Results 49% of cases tested positive for at least one virus, of whom 10% had multiple infections. 53% of the FRI cases fulfilled the definition of influenza-like illness (ILI), of whom 52% were positive for at least one virus. The most frequent etiologies for mono-infections among FRI cases were Influenza A(H1N1)pdm09 (13%), Influenza B (13%) and coxsackevirus (9%). The sensitivity, specificity, positive predictive value and negative predictive value of ILI for influenza among FRI cases were 72%, 48%, 40% and 69% respectively. On logistic regression, there were marked differences in the prevalence of different symptoms and signs between viruses with fever more prevalent amongst influenza and adenovirus infections than other viruses. Conclusion There are multiple viral etiologies for FRI and ILI with differing clinical symptoms in the Singapore military. Influenza and coxsackevirus were the most common etiology for FRI, while influenza and adenoviruses displayed the most febrile symptoms. Further studies should explore these differences and possible interventions. PMID:24735158

  7. Low-level detection of viral pathogens by a surface-enhanced Raman scattering based immunoassay.

    PubMed

    Driskell, Jeremy D; Kwarta, Karen M; Lipert, Robert J; Porter, Marc D; Neill, John D; Ridpath, Julia F

    2005-10-01

    The need for rapid, highly sensitive, and versatile diagnostic tests for viral pathogens spans from human and veterinary medicine to bioterrorism prevention. As an approach to meet these demands, a diagnostic test employing monoclonal antibodies (mAbs) for the selective extraction of viral pathogens from a sample in a chip-scale, sandwich immunoassay format has been developed using surface-enhanced Raman scattering (SERS) as a readout method. The strengths of SERS-based detection include its inherent high sensitivity and facility for multiplexing. The capability of this approach is demonstrated by the capture of feline calicivirus (FCV) from cell culture media that is exposed to a gold substrate modified with a covalently immobilized layer of anti-FCV mAbs. The surface-bound FCVs are subsequently coupled with an extrinsic Raman label (ERL) for identification and quantification. The ERLs consist of 60-nm gold nanoparticles coated first with a layer of Raman reporter molecules and then a layer of mAbs. The Raman reporter molecule is strategically designed to chemisorb as a thiolate adlayer on the gold nanoparticle, to provide a strong and unique spectral signature, and to covalently link a layer of mAbs to the gold nanoparticle. The last feature provides a means to selectively tag substrate-bound FCV. This paper describes the development of the assay, which uses cell culture media as a sample matrix and has a linear dynamic range of 1 x 10(6)-2.5 x 10(8) viruses/mL and a limit of detection of 1 x 10(6) viruses/mL. These results reflect the findings from a detailed series of investigations on the effects of several experimental parameters (e.g., salt concentration, ERL binding buffer, and sample agitation), all of which were aimed at minimizing nonspecific binding and maximizing FCV binding efficiency. The performance of the assay is correlated with the number of captured FCV, determined by atomic force microscopy, as a means of method validation. PMID:16194072

  8. Phosphorylation of a Herpes Simplex Virus 1 dUTPase by a Viral Protein Kinase, Us3, Dictates Viral Pathogenicity in the Central Nervous System but Not at the Periphery

    PubMed Central

    Kato, Akihisa; Shindo, Keiko; Maruzuru, Yuhei

    2014-01-01

    ABSTRACT Herpes simplex virus 1 (HSV-1) encodes Us3 protein kinase, which is critical for viral pathogenicity in both mouse peripheral sites (e.g., eyes and vaginas) and in the central nervous systems (CNS) of mice after intracranial and peripheral inoculations, respectively. Whereas some Us3 substrates involved in Us3 pathogenicity in peripheral sites have been reported, those involved in Us3 pathogenicity in the CNS remain to be identified. We recently reported that Us3 phosphorylated HSV-1 dUTPase (vdUTPase) at serine 187 (Ser-187) in infected cells, and this phosphorylation promoted viral replication by regulating optimal enzymatic activity of vdUTPase. In the present study, we show that the replacement of vdUTPase Ser-187 by alanine (S187A) significantly reduced viral replication and virulence in the CNS of mice following intracranial inoculation and that the phosphomimetic substitution at vdUTPase Ser-187 in part restored the wild-type viral replication and virulence. Interestingly, the S187A mutation in vdUTPase had no effect on viral replication and pathogenic effects in the eyes and vaginas of mice after ocular and vaginal inoculation, respectively. Similarly, the enzyme-dead mutation in vdUTPase significantly reduced viral replication and virulence in the CNS of mice after intracranial inoculation, whereas the mutation had no effect on viral replication and pathogenic effects in the eyes and vaginas of mice after ocular and vaginal inoculation, respectively. These observations suggested that vdUTPase was one of the Us3 substrates responsible for Us3 pathogenicity in the CNS and that the CNS-specific virulence of HSV-1 involved strict regulation of vdUTPase activity by Us3 phosphorylation. IMPORTANCE Herpes simplex virus 1 (HSV-1) encodes a viral protein kinase Us3 which is critical for pathogenicity both in peripheral sites and in the central nervous systems (CNS) of mice following peripheral and intracranial inoculations, respectively. Whereas some Us3 substrates involved in Us3 pathogenicity in peripheral sites have been reported, those involved in Us3 pathogenicity in the CNS remain to be identified. Here, we report that Us3 phosphorylation of viral dUTPase (vdUTPase) at serine 187 (Ser-187), which has been shown to promote the vdUTPase activity, appears to be critical for viral virulence in the CNS but not for pathogenic effects in peripheral sites. Since HSV proteins critical for viral virulence in the CNS are, in almost all cases, also involved in viral pathogenicity at peripheral sites, this phosphorylation event is a unique report of a specific mechanism involved in HSV-1 virulence in the CNS. PMID:24352467

  9. Amphibian ranaviruses in Canada historical, current and future research

    E-print Network

    Gray, Matthew

    : Lithobates sylvaticus L pipiens 1) host range and geographic range L. pipiens L. clamitans Ranavirus assumed infections (L. pipiens) David Lesbarreres Lab & collaborators, this symposium Cam Goater, U Lethbridge ATV

  10. Comparative study of ranavirus isolates from cod ( Gadus morhua ) and turbot ( Psetta maxima ) with reference to other ranaviruses

    Microsoft Academic Search

    Ellen Ariel; Riikka Holopainen; Niels Jørgen Olesen; Hannele Tapiovaara

    2010-01-01

    Two iridovirus isolates recovered from cod (Gadus morhua) and turbot (Psetta maxima) in Denmark were examined in parallel with a panel of other ranaviruses including frog virus 3 (FV3), the reference strain\\u000a for the genus Ranavirus. The isolates were assessed according to their reactivity in immunofluoresent antibody tests (IFAT) using both homologous\\u000a and heterologous antisera and their amplification in PCR

  11. First Report of a Ranavirus Associated with Morbidity and Mortality in Farmed Chinese Giant

    E-print Network

    Gray, Matthew

    -like particles within the inclusions. Of the six specimens tested, all were positive for ranavirus major capsid protein (MCP) gene. Sequence alignments of the ranavirus MCP gene from these specimens showed 95e98 salamander; iridovirus; pathology; ranavirus Introduction Iridoviruses are large enveloped viruses

  12. Seroprevalences to viral pathogens in free-ranging and captive cheetahs (Acinonyx jubatus) on Namibian Farmland.

    PubMed

    Thalwitzer, Susanne; Wachter, Bettina; Robert, Nadia; Wibbelt, Gudrun; Müller, Thomas; Lonzer, Johann; Meli, Marina L; Bay, Gert; Hofer, Heribert; Lutz, Hans

    2010-02-01

    Cheetah populations are diminishing rapidly in their natural habitat. One reason for their decline is thought to be a high susceptibility to (infectious) diseases because cheetahs in zoos suffer from high disease-induced mortality. Data on the health status of free-ranging cheetahs are scarce, and little is known about their exposure and susceptibility to infectious diseases. We determined seroprevalences to nine key viruses (feline herpesvirus 1, feline calicivirus, feline parvovirus, feline coronavirus, canine distemper virus, feline immunodeficiency virus [FIV], puma lentivirus, feline leukemia virus, and rabies virus) in 68 free-ranging cheetahs on east-central Namibian farmland, 24 nonvaccinated Namibian captive cheetahs, and several other wild carnivore species and conducted necropsies of cheetahs and other wild carnivores. Eight of 11 other wild carnivores were seropositive for at least one of the viruses, including the first record of an FIV-like infection in a wild felid west of the Kalahari, the caracal (Felis caracal). Seroprevalences of the free-ranging cheetahs were below 5% for all nine viruses, which is significantly lower than seroprevalences in nonvaccinated captive cheetahs and those for five of seven viruses in previously studied free-ranging cheetahs from north-central Namibia (L. Munson, L. Marker, E. Dubovi, J. A. Spencer, J. F. Evermann, and S. J. O'Brien, J. Wildl. Dis. 40:23-31, 2004). There was no clinical or pathological evidence of infectious diseases in living or dead cheetahs. The results suggest that while free-ranging wild carnivores may be a source of pathogens, the distribution of seroprevalences across studies mirrored local human population density and factors associated with human habitation, probably reflecting contact opportunities with (nonvaccinated) domestic and feral cats and dogs. They also suggest that Namibian cheetahs respond effectively to viral challenges, encouraging consistent and sustainable conservation efforts. PMID:19955325

  13. Viral Pathogen-Associated Molecular Patterns Regulate Blood-Brain Barrier Integrity via Competing Innate Cytokine Signals

    PubMed Central

    Daniels, Brian P.; Holman, David W.; Cruz-Orengo, Lillian; Jujjavarapu, Harsha; Durrant, Douglas M.

    2014-01-01

    ABSTRACT Pattern recognition receptor (PRR) detection of pathogen-associated molecular patterns (PAMPs), such as viral RNA, drives innate immune responses against West Nile virus (WNV), an emerging neurotropic pathogen. Here we demonstrate that WNV PAMPs orchestrate endothelial responses to WNV via competing innate immune cytokine signals at the blood-brain barrier (BBB), a multicellular interface with highly specialized brain endothelial cells that normally prevents pathogen entry. While Th1 cytokines increase the permeability of endothelial barriers, type I interferon (IFN) promoted and stabilized BBB function. Induction of innate cytokines by pattern recognition pathways directly regulated BBB permeability and tight junction formation via balanced activation of the small GTPases Rac1 and RhoA, which in turn regulated the transendothelial trafficking of WNV. In vivo, mice with attenuated type I IFN signaling or IFN induction (Ifnar?/? Irf7?/?) exhibited enhanced BBB permeability and tight junction dysregulation after WNV infection. Together, these data provide new insight into host-pathogen interactions at the BBB during neurotropic viral infection. PMID:25161189

  14. Methods and compositions for identifying cellular genes exploited by viral pathogens.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methods and compositions for rapidly identifying CGEPs required for viral infection of mammalian cells are provided. Also provided are methods of inhibiting viral infection of mammalian cells by inhibiting the activity of one or more CGEPs (e.g., as identified in accordance with methods of the inve...

  15. [Detection of viral infection pathogens in medicinal plants grown in Ukraine].

    PubMed

    Mishchenko, L T; Korenieva, A A; Molchanets', O V; Bo?ko, A L

    2009-01-01

    Monitoring of viral infection on medicinal plant plantations is carried out. Panax ginseng C.A. Meyer, Valeriana officinalis L., Plantago major L. with symptoms of viral infection were revealed. Viral nature of symptoms was proved with biotesting method. Morphology and sizes of virus particles, detected in Panax ginseng method. Morphology and sizes of virus particles, detected in Panax ginseng C.A. Meyer, Valeriana officinalis L., Plantago major L., were determined with electron microscopy method. The paper is presented in Ukrainian. PMID:19938607

  16. INCREASING LEVELS OF ENVIRONMENTAL MUTAGENS: POTENTIAL FOR AFFECTING VIRAL EVOLUTION AND PATHOGENICITY - A SPECULATIVE REVIEW

    EPA Science Inventory

    The author examines available data concerning the ways in which information contained in viral genomes is altered. echanisms of damage and repair of nucleic acids are discussed. nformation available on the rates of evolution of various viruses is summarized....

  17. Mutagenesis-Mediated Decrease of Pathogenicity as a Feature of the Mutant Spectrum of a Viral Population

    PubMed Central

    Sanz-Ramos, Marta; Rodríguez-Calvo, Teresa; Sevilla, Noemí

    2012-01-01

    Background RNA virus populations are heterogeneous ensembles of closely related genomes termed quasispecies. This highly complex distribution of variants confers important properties to RNA viruses and influences their pathogenic behavior. It has been hypothesized that increased mutagenesis of viral populations, by treatment with mutagenic agents, can induce alterations in the pathogenic potential of a virus population. In this work we investigate whether mutagenized foot-and-mouth disease virus (FMDV) populations display changes in their virulence in mice. Methodology and Principal Findings FMDV C-S8c1 was passaged in BHK cells in the presence of the mutagenic agent ribavirin. Decline in viral titer and viral RNA progeny was observed in the first passage, fluctuating around a constant value thereafter. Hence, the specific infectivity remained stable during the passages. The viral population harvested from passage 9 (P9 R) showed decreased virulence in mice, with a lethal dose 50 (LD50) >104 PFU, as compared with LD50 of 50 PFU of the parental population FMDV C-S8c1. This decrease in virulence was associated to a 20-fold increase in the mutation frequency of the P9 R population with respect to C-S8c1. Interestingly, individual biological clones isolated from the attenuated population P9 R were as virulent as the parental virus C-S8c1. Furthermore, a mixed population of C-S8c1 and P9 R was inoculated into mice and showed decreased virulence as compared to C-S8c1, suggesting that population P9 R is able to suppress the virulent phenotype of C-S8c1. Conclusion Ribavirin-mediated mutagenesis of an FMDV population resulted in attenuation in vivo, albeit a large proportion of its biological clones displayed a highly virulent phenotype. These results, together with the suppression of C-S8c1 by mutagenized P9 R population, document a suppressive effect of mutagenized viral quasispecies in vivo, and suggest novel approaches to the treatment and prevention of viral diseases. PMID:22761933

  18. The effects of immunosuppression on the pathogenicity of viral arthritis virus of chickens

    E-print Network

    Pugh, Roberta Ann

    1979-01-01

    these changes are characterized by edema, coagulation necrosis and heter ophil accumulation (28). In chronic infection, there is usually an in- creased accumulation of fibrous connective tissues, pronounced infiltration of reticular cells and accumulation..., closely resemble those seen in chickens with viral arthritis. As seen in chickens with viral arthritis, character istic histopathological changes of rheumatoid arthritis are edema, pronounced infiltration of reticular cells, synovial membrane cell...

  19. Coinfection of tick cell lines has variable effects on replication of intracellular bacterial and viral pathogens

    PubMed Central

    Moniuszko, Anna; Rückert, Claudia; Alberdi, M. Pilar; Barry, Gerald; Stevenson, Brian; Fazakerley, John K.; Kohl, Alain; Bell-Sakyi, Lesley

    2014-01-01

    Ticks transmit various human and animal microbial pathogens and may harbour more than one pathogen simultaneously. Both viruses and bacteria can trigger, and may subsequently suppress, vertebrate host and arthropod vector anti-microbial responses. Microbial coinfection of ticks could lead to an advantage or disadvantage for one or more of the microorganisms. In this preliminary study, cell lines derived from the ticks Ixodes scapularis and Ixodes ricinus were infected sequentially with 2 arthropod-borne pathogens, Borrelia burgdorferi s.s., Ehrlichia ruminantium, or Semliki Forest virus (SFV), and the effect of coinfection on the replication of these pathogens was measured. Prior infection of tick cell cultures with the spirochaete B. burgdorferi enhanced subsequent replication of the rickettsial pathogen E. ruminantium whereas addition of spirochaetes to cells infected with E. ruminantium had no effect on growth of the latter. Both prior and subsequent presence of B. burgdorferi also had a positive effect on SFV replication. Presence of E. ruminantium or SFV had no measurable effect on B. burgdorferi growth. In tick cells infected first with E. ruminantium and then with SFV, virus replication was significantly higher across all time points measured (24, 48, 72 h post infection), while presence of the virus had no detectable effect on bacterial growth. When cells were infected first with SFV and then with E. ruminantium, there was no effect on replication of either pathogen. The results of this preliminary study indicate that interplay does occur between different pathogens during infection of tick cells. Further study is needed to determine if this results from direct pathogen–pathogen interaction or from effects on host cell defences, and to determine if these observations also apply in vivo in ticks. If presence of one pathogen in the tick vector results in increased replication of another, this could have implications for disease transmission and incidence. PMID:24685441

  20. Coinfection of tick cell lines has variable effects on replication of intracellular bacterial and viral pathogens.

    PubMed

    Moniuszko, Anna; Rückert, Claudia; Alberdi, M Pilar; Barry, Gerald; Stevenson, Brian; Fazakerley, John K; Kohl, Alain; Bell-Sakyi, Lesley

    2014-06-01

    Ticks transmit various human and animal microbial pathogens and may harbour more than one pathogen simultaneously. Both viruses and bacteria can trigger, and may subsequently suppress, vertebrate host and arthropod vector anti-microbial responses. Microbial coinfection of ticks could lead to an advantage or disadvantage for one or more of the microorganisms. In this preliminary study, cell lines derived from the ticks Ixodes scapularis and Ixodes ricinus were infected sequentially with 2 arthropod-borne pathogens, Borrelia burgdorferi s.s., Ehrlichia ruminantium, or Semliki Forest virus (SFV), and the effect of coinfection on the replication of these pathogens was measured. Prior infection of tick cell cultures with the spirochaete B. burgdorferi enhanced subsequent replication of the rickettsial pathogen E. ruminantium whereas addition of spirochaetes to cells infected with E. ruminantium had no effect on growth of the latter. Both prior and subsequent presence of B. burgdorferi also had a positive effect on SFV replication. Presence of E. ruminantium or SFV had no measurable effect on B. burgdorferi growth. In tick cells infected first with E. ruminantium and then with SFV, virus replication was significantly higher across all time points measured (24, 48, 72h post infection), while presence of the virus had no detectable effect on bacterial growth. When cells were infected first with SFV and then with E. ruminantium, there was no effect on replication of either pathogen. The results of this preliminary study indicate that interplay does occur between different pathogens during infection of tick cells. Further study is needed to determine if this results from direct pathogen-pathogen interaction or from effects on host cell defences, and to determine if these observations also apply in vivo in ticks. If presence of one pathogen in the tick vector results in increased replication of another, this could have implications for disease transmission and incidence. PMID:24685441

  1. Differential Responses of Plasmacytoid Dendritic Cells to Influenza Virus and Distinct Viral Pathogens

    PubMed Central

    Thomas, Jaime M.; Pos, Zoltan; Reinboth, Jennifer; Wang, Richard Y.; Wang, Ena; Frank, Gregory M.; Lusso, Paolo; Trinchieri, Giorgio; Alter, Harvey J.

    2014-01-01

    ABSTRACT Plasmacytoid dendritic cells (pDCs) are key components of the innate immune response that are capable of synthesizing and rapidly releasing vast amounts of type I interferons (IFNs), particularly IFN-?. Here we investigated whether pDCs, often regarded as a mere source of IFN, discriminate between various functionally discrete stimuli and to what extent this reflects differences in pDC responses other than IFN-? release. To examine the ability of pDCs to differentially respond to various doses of intact and infectious HIV, hepatitis C virus, and H1N1 influenza virus, whole-genome gene expression analysis, enzyme-linked immunosorbent assays, and flow cytometry were used to investigate pDC responses at the transcriptional, protein, and cellular levels. Our data demonstrate that pDCs respond differentially to various viral stimuli with significant changes in gene expression, including those involved in pDC activation, migration, viral endocytosis, survival, or apoptosis. In some cases, the expression of these genes was induced even at levels comparable to that of IFN-?. Interestingly, we also found that depending on the viral entity and the viral titer used for stimulation, induction of IFN-? gene expression and the actual release of IFN-? are not necessarily temporally coordinated. In addition, our data suggest that high-titer influenza A (H1N1) virus infection can stimulate rapid pDC apoptosis. IMPORTANCE Plasmacytoid dendritic cells (pDCs) are key players in the viral immune response. With the host response to viral infection being dependent on specific virus characteristics, a thorough examination and comparison of pDC responses to various viruses at various titers is beneficial for the field of virology. Our study illustrates that pDC infection with influenza virus, HIV, or hepatitis C virus results in a unique and differential response to each virus. These results have implications for future virology research, vaccine development, and virology as a whole. PMID:25008918

  2. Mutations in the cytoplasmic domain of the Newcastle disease virus fusion protein confer hyperfusogenic phenotypes modulating viral replication and pathogenicity.

    PubMed

    Samal, Sweety; Khattar, Sunil K; Paldurai, Anandan; Palaniyandi, Senthilkumar; Zhu, Xiaoping; Collins, Peter L; Samal, Siba K

    2013-09-01

    The Newcastle disease virus (NDV) fusion protein (F) mediates fusion of viral and host cell membranes and is a major determinant of NDV pathogenicity. In the present study, we demonstrate the effects of functional properties of F cytoplasmic tail (CT) amino acids on virus replication and pathogenesis. Out of a series of C-terminal deletions in the CT, we were able to rescue mutant viruses lacking two or four residues (r?2 and r?4). We further rescued viral mutants with individual amino acid substitutions at each of these four terminal residues (rM553A, rK552A, rT551A, and rT550A). In addition, the NDV F CT has two conserved tyrosine residues (Y524 and Y527) and a dileucine motif (LL536-537). In other paramyxoviruses, these residues were shown to affect fusion activity and are central elements in basolateral targeting. The deletion of 2 and 4 CT amino acids and single tyrosine substitution resulted in hyperfusogenic phenotypes and increased viral replication and pathogenesis. We further found that in rY524A and rY527A viruses, disruption of the targeting signals did not reduce the expression on the apical or basolateral surface in polarized Madin-Darby canine kidney cells, whereas in double tyrosine mutant, it was reduced on both the apical and basolateral surfaces. Interestingly, in rL536A and rL537A mutants, the F protein expression was more on the apical than on the basolateral surface, and this effect was more pronounced in the rL537A mutant. We conclude that these wild-type residues in the NDV F CT have an effect on regulating F protein biological functions and thus modulating viral replication and pathogenesis. PMID:23843643

  3. Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part I: Overview, vaccines for enteric viruses and Vibrio cholerae.

    PubMed

    O'Ryan, Miguel; Vidal, Roberto; Del Canto, Felipe; Salazar, Juan Carlos; Montero, David

    2015-03-01

    Efforts to develop vaccines for prevention of acute diarrhea have been going on for more than 40 y with partial success. The myriad of pathogens, more than 20, that have been identified as a cause of acute diarrhea throughout the years pose a significant challenge for selecting and further developing the most relevant vaccine candidates. Based on pathogen distribution as identified in epidemiological studies performed mostly in low-resource countries, rotavirus, Cryptosporidium, Shigella, diarrheogenic E. coli and V. cholerae are predominant, and thus the main targets for vaccine development and implementation. Vaccination against norovirus is most relevant in middle/high-income countries and possibly in resource-deprived countries, pending a more precise characterization of disease impact. Only a few licensed vaccines are currently available, of which rotavirus vaccines have been the most outstanding in demonstrating a significant impact in a short time period. This is a comprehensive review, divided into 2 articles, of nearly 50 vaccine candidates against the most relevant viral and bacterial pathogens that cause acute gastroenteritis. In order to facilitate reading, sections for each pathogen are organized as follows: i) a discussion of the main epidemiological and pathogenic features; and ii) a discussion of vaccines based on their stage of development, moving from current licensed vaccines to vaccines in advanced stage of development (in phase IIb or III trials) to vaccines in early stages of clinical development (in phase I/II) or preclinical development in animal models. In this first article we discuss rotavirus, norovirus and Vibrio cholerae. In the following article we will discuss Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic), and Campylobacter jejuni. PMID:25715048

  4. BOVINE VIRAL DIARRHEA VIRUS IN CAMELIDS: AN EMERGING PATHOGEN AND WAYS TO MONITOR HERD INFECTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The subject of this report will attempt to tie in several aspects of bovine viral diarrhea virus (BVDV) and its most recent incursion into the camelid family, namely llamas and alpacas. We have known that both llamas and alpacas are susceptible to BVDV infections for over 20 years. In some cases, ...

  5. Torque teno virus: an improved indicator for viral pathogens in drinking waters

    Microsoft Academic Search

    Jennifer S Griffin; Jeanine D Plummer; Sharon C Long

    2008-01-01

    BACKGROUND: Currently applied indicator organism systems, such as coliforms, are not fully protective of public health from enteric viruses in water sources. Waterborne disease outbreaks have occurred in systems that tested negative for coliforms, and positive coliform results do not necessarily correlate with viral risk. It is widely recognized that bacterial indicators do not co-occur exclusively with infectious viruses, nor

  6. Are Ranaviruses Capable of Contributing to Species Declines?

    E-print Network

    Gray, Matthew

    ·Ambystoma tigrinum stebbinsi (1985, 1997) #12;2 Global Distribution of Ranavirus Die-offs All Latitudes, All Uncommon Southeastern United States Federally Listed: Rana capito sevosa, Ambystoma cingulatum, Phaeognathus hubrichti, Ambystoma bishopi Species of Concern: 113 Species and 25 Genera Total 1) Alabama = 14

  7. Distribution of an invasive aquatic pathogen (viral hemorrhagic septicemia virus) in the Great Lakes and its relationship to shipping

    USGS Publications Warehouse

    Bain, Mark B.; Cornwell, Emily R.; Hope, Kristine M.; Eckerlin, Geofrey E.; Casey, Rufina N.; Groocock, Geoffrey H.; Getchell, Rodman G.; Bowser, Paul R.; Winton, James R.; Batts, William N.; Cangelosi, Allegra; Casey, James W.

    2010-01-01

    Viral hemorrhagic septicemia virus (VHSV) is a rhabdovirus found in fish from oceans of the northern hemisphere and freshwaters of Europe. It has caused extensive losses of cultured and wild fish and has become established in the North American Great Lakes. Large die-offs of wild fish in the Great Lakes due to VHSV have alarmed the public and provoked government attention on the introduction and spread of aquatic animal pathogens in freshwaters. We investigated the relations between VHSV dispersion and shipping and boating activity in the Great Lakes by sampling fish and water at sites that were commercial shipping harbors, recreational boating centers, and open shorelines. Fish and water samples were individually analyzed for VHSV using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and cell culture assays. Of 1,221 fish of 17 species, 55 were VHSV positive with highly varied qRT-PCR titers (1 to 5,950,000 N gene copies). The detections of VHSV in fish and water samples were closely associated and the virus was detected in 21 of 30 sites sampled. The occurrence of VHSV was not related to type of site or shipping related invasion hotspots. Our results indicate that VHSV is widely dispersed in the Great Lakes and is both an enzootic and epizootic pathogen. We demonstrate that pathogen distribution information could be developed quickly and is clearly needed for aquatic ecosystem conservation, management of affected populations, and informed regulation of the worldwide trade of aquatic organisms.

  8. Distribution of an invasive aquatic pathogen (viral hemorrhagic septicemia virus) in the Great Lakes and its relationship to shipping.

    PubMed

    Bain, Mark B; Cornwell, Emily R; Hope, Kristine M; Eckerlin, Geofrey E; Casey, Rufina N; Groocock, Geoffrey H; Getchell, Rodman G; Bowser, Paul R; Winton, James R; Batts, William N; Cangelosi, Allegra; Casey, James W

    2010-01-01

    Viral hemorrhagic septicemia virus (VHSV) is a rhabdovirus found in fish from oceans of the northern hemisphere and freshwaters of Europe. It has caused extensive losses of cultured and wild fish and has become established in the North American Great Lakes. Large die-offs of wild fish in the Great Lakes due to VHSV have alarmed the public and provoked government attention on the introduction and spread of aquatic animal pathogens in freshwaters. We investigated the relations between VHSV dispersion and shipping and boating activity in the Great Lakes by sampling fish and water at sites that were commercial shipping harbors, recreational boating centers, and open shorelines. Fish and water samples were individually analyzed for VHSV using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and cell culture assays. Of 1,221 fish of 17 species, 55 were VHSV positive with highly varied qRT-PCR titers (1 to 5,950,000 N gene copies). The detections of VHSV in fish and water samples were closely associated and the virus was detected in 21 of 30 sites sampled. The occurrence of VHSV was not related to type of site or shipping related invasion hotspots. Our results indicate that VHSV is widely dispersed in the Great Lakes and is both an enzootic and epizootic pathogen. We demonstrate that pathogen distribution information could be developed quickly and is clearly needed for aquatic ecosystem conservation, management of affected populations, and informed regulation of the worldwide trade of aquatic organisms. PMID:20405014

  9. Distribution of an Invasive Aquatic Pathogen (Viral Hemorrhagic Septicemia Virus) in the Great Lakes and Its Relationship to Shipping

    PubMed Central

    Bain, Mark B.; Cornwell, Emily R.; Hope, Kristine M.; Eckerlin, Geofrey E.; Casey, Rufina N.; Groocock, Geoffrey H.; Getchell, Rodman G.; Bowser, Paul R.; Winton, James R.; Batts, William N.; Cangelosi, Allegra; Casey, James W.

    2010-01-01

    Viral hemorrhagic septicemia virus (VHSV) is a rhabdovirus found in fish from oceans of the northern hemisphere and freshwaters of Europe. It has caused extensive losses of cultured and wild fish and has become established in the North American Great Lakes. Large die-offs of wild fish in the Great Lakes due to VHSV have alarmed the public and provoked government attention on the introduction and spread of aquatic animal pathogens in freshwaters. We investigated the relations between VHSV dispersion and shipping and boating activity in the Great Lakes by sampling fish and water at sites that were commercial shipping harbors, recreational boating centers, and open shorelines. Fish and water samples were individually analyzed for VHSV using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and cell culture assays. Of 1,221 fish of 17 species, 55 were VHSV positive with highly varied qRT-PCR titers (1 to 5,950,000 N gene copies). The detections of VHSV in fish and water samples were closely associated and the virus was detected in 21 of 30 sites sampled. The occurrence of VHSV was not related to type of site or shipping related invasion hotspots. Our results indicate that VHSV is widely dispersed in the Great Lakes and is both an enzootic and epizootic pathogen. We demonstrate that pathogen distribution information could be developed quickly and is clearly needed for aquatic ecosystem conservation, management of affected populations, and informed regulation of the worldwide trade of aquatic organisms. PMID:20405014

  10. USING SYNTHETIC PYRETHROIDS TO PROTECT LIVESTOCK FROM INSECT BLOOD-FEEDING AND TRANSMISSION OF VIRAL PATHOGENS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The vulnerability of US livestock to introduction of exotic insect-transmitted pathogens is recognized as a major threat to U.S. agriculture. Rift Valley Fever virus (RVFv) is rated the highest threat to animal agriculture in the Americas based on economic and public health implications, the availab...

  11. DEVELOPMENT OF A BIOMARKER SYSTEM FOR DETECTING EXPOSURE TO WATERBORNE VIRAL PATHOGENS

    EPA Science Inventory

    EPA has published a drinking water contaminant candidate list (CCL) that includes waterborne pathogens and chemicals that may be considered for regulation at a future date. For each contaminant on the CCL, the Agency will need sufficient data to conduct analyses on the extent of...

  12. Production of transgenic rainbow trout resistant to infection by bacterial and viral pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exploiting the natural microbe-defense (innate defense) mechanism, originally discovered in insects and subsequently found in many animal species, may lead to the development of a novel approach for protecting commercially important finfish and crustacean species from infection by microbial pathogen...

  13. Recognition of the Hyaloperonospora parasitica effector ATR13 triggers resistance against oomycete, bacterial, and viral pathogens

    Microsoft Academic Search

    Maike C. Rentel; Lauriebeth Leonelli; Douglas Dahlbeck; Bingyu Zhao; Brian J. Staskawicz

    2008-01-01

    Phytopathogenic oomycetes cause some of the most devastating diseases affecting agricultural crops. Hyaloperonospora parasitica is a native oomycete pathogen of Arabidopsis and is related to other oomycete phytopathogens that include several species of Phytophthora, including the causal agent of potato late blight. Recently, four oomycete effector genes have been isolated, and several oomycete genomes have been sequenced. We have developed

  14. Intact Dendritic Cell Pathogen-Recognition Receptor Functions Associate with Chronic Hepatitis C Treatment-Induced Viral Clearance

    PubMed Central

    Rodrigue-Gervais, Ian Gaël; Willems, Bernard; Lamarre, Daniel

    2014-01-01

    Although studies have addressed the exhaustion of the host's immune response to HCV and its role in treatment, there is little information about the possible contribution of innate immunity to treatment-induced clearance. We hypothesized that because intact myeloid dendritic cell (MDC) pathogen sensing functions are associated with improved HCV-specific CD8+ T cell functionality in some chronically infected patients, it might enhance HCV clearance rate under standard interferon therapy. To investigate this hypothesis, TLR-induced MDC activation and HCV-specific CD8+ T cell response quality were monitored longitudinally at the single-cell level using polychromatic flow cytometry in chronically infected patients undergoing interferon therapy. We correlated the immunological, biochemical and virological data with response to treatment. We demonstrate that the clinical efficacy of interferon-induced viral clearance is influenced by the extent to which HCV inhibits MDC functions before treatment, rather than solely on a breakdown of the extrinsic T cell immunosuppressive environment. Thus, viral inhibition of MDC functions before treatment emerges as a co-determining factor in the clinical efficacy of interferon therapy during chronic HCV infection. PMID:25033043

  15. Bacterial and Viral Pathogens in Live Oysters: 2007 United States Market Survey ?

    PubMed Central

    DePaola, Angelo; Jones, Jessica L.; Woods, Jacquelina; Burkhardt, William; Calci, Kevin R.; Krantz, Jeffrey A.; Bowers, John C.; Kasturi, Kuppuswamy; Byars, Robin H.; Jacobs, Emily; Williams-Hill, Donna; Nabe, Khamphet

    2010-01-01

    Two samples of market oysters, primarily from retail establishments, were collected twice each month in each of nine states during 2007. Samples were shipped refrigerated overnight to five U.S. Food and Drug Administration laboratories on a rotating basis and analyzed by most probable number (MPN) for total and pathogenic Vibrio parahaemolyticus and V. vulnificus numbers and for the presence of toxigenic V. cholerae, Salmonella spp., norovirus (NoV), and hepatitis A virus (HAV). Levels of indicator organisms, including fecal coliforms (MPN), Escherichia coli (MPN), male-specific bacteriophage, and aerobic plate counts, were also determined. V. parahaemolyticus and V. vulnificus levels were distributed seasonally and geographically by harvest region and were similar to levels observed in a previous study conducted in 1998-1999. Levels of pathogenic V. parahaemolyticus were typically several logs lower than total V. parahaemolyticus levels regardless of season or region. Pathogenic V. parahaemolyticus levels in the Gulf and Mid-Atlantic regions were about two logs greater than the levels observed in the Pacific and North Atlantic regions. Pathogens generally associated with fecal pollution were detected sporadically or not at all (toxigenic V. cholerae, 0%; Salmonella, 1.5%; NoV, 3.9%; HAV, 4.4%). While seasonal prevalences of NoV and HAV were generally greater in oysters harvested from December to March, the low detection frequency obscured any apparent seasonal effects. Overall, there was no relationship between the levels of indicator microorganisms and the presence of enteric viruses. These data provide a baseline that can be used to further validate risk assessment predictions, determine the effectiveness of new control measures, and compare the level of protection provided by the U.S. shellfish sanitation system to those in other countries. PMID:20190085

  16. 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

  17. HandGun-mediated inoculation of plants with viral pathogens for mechanistic studies.

    PubMed

    Gaba, Victor; Lapidot, Moshe; Gal-On, Amit

    2013-01-01

    Particle bombardment is an efficient method for virus inoculation of intact plants. This technique enables inoculation with full-length infectious clone cDNA, PCR products, virus from sap or virus preparation, and in vitro viral transcripts. The inoculation of some phloem-limited RNA and circular DNA viruses is also possible. The technique of bombardment without the use of vacuum permits the inoculation of soft-leaved plants that do not usually survive bombardment inoculation, the investigation of viral recombination in planta, promoter analysis, monitoring virus movement using an infectious clone bearing a reporter gene and the inoculation of large numbers of plants. The inoculation of whitefly-borne circular DNA begomoviruses is now possible due to direct genome amplification by Rolling Circle Amplification (RCA), followed by bombardment using a device that does not require a vacuum for operation. Here we describe the inoculation of intact plants with (a) RNA virus infective clones and (b) begomoviruses after direct genome amplification by RCA, using a handheld bombardment device. PMID:23104333

  18. In Search of Pathogens: Transcriptome-Based Identification of Viral Sequences from the Pine Processionary Moth (Thaumetopoea pityocampa)

    PubMed Central

    Jakubowska, Agata K.; Nalcacioglu, Remziye; Millán-Leiva, Anabel; Sanz-Carbonell, Alejandro; Muratoglu, Hacer; Herrero, Salvador; Demirbag, Zihni

    2015-01-01

    Thaumetopoea pityocampa (pine processionary moth) is one of the most important pine pests in the forests of Mediterranean countries, Central Europe, the Middle East and North Africa. Apart from causing significant damage to pinewoods, T. pityocampa occurrence is also an issue for public and animal health, as it is responsible for dermatological reactions in humans and animals by contact with its irritating hairs. High throughput sequencing technologies have allowed the fast and cost-effective generation of genetic information of interest to understand different biological aspects of non-model organisms as well as the identification of potential pathogens. Using these technologies, we have obtained and characterized the transcriptome of T. pityocampa larvae collected in 12 different geographical locations in Turkey. cDNA libraries for Illumina sequencing were prepared from four larval tissues, head, gut, fat body and integument. By pooling the sequences from Illumina platform with those previously published using the Roche 454-FLX and Sanger methods we generated the largest reference transcriptome of T. pityocampa. In addition, this study has also allowed identification of possible viral pathogens with potential application in future biocontrol strategies. PMID:25626148

  19. In Search of Pathogens: Transcriptome-Based Identification of Viral Sequences from the Pine Processionary Moth (Thaumetopoea pityocampa).

    PubMed

    Jakubowska, Agata K; Nalcacioglu, Remziye; Millán-Leiva, Anabel; Sanz-Carbonell, Alejandro; Muratoglu, Hacer; Herrero, Salvador; Demirbag, Zihni

    2015-01-01

    Thaumetopoea pityocampa (pine processionary moth) is one of the most important pine pests in the forests of Mediterranean countries, Central Europe, the Middle East and North Africa. Apart from causing significant damage to pinewoods, T. pityocampa occurrence is also an issue for public and animal health, as it is responsible for dermatological reactions in humans and animals by contact with its irritating hairs. High throughput sequencing technologies have allowed the fast and cost-effective generation of genetic information of interest to understand different biological aspects of non-model organisms as well as the identification of potential pathogens. Using these technologies, we have obtained and characterized the transcriptome of T. pityocampa larvae collected in 12 different geographical locations in Turkey. cDNA libraries for Illumina sequencing were prepared from four larval tissues, head, gut, fat body and integument. By pooling the sequences from Illumina platform with those previously published using the Roche 454-FLX and Sanger methods we generated the largest reference transcriptome of T. pityocampa. In addition, this study has also allowed identification of possible viral pathogens with potential application in future biocontrol strategies. PMID:25626148

  20. Studies on the effect of temperature and pH on the inactivation of fish viral and bacterial pathogens.

    PubMed

    Dixon, P F; Smail, D A; Algoët, M; Hastings, T S; Bayley, A; Byrne, H; Dodge, M; Garden, A; Joiner, C; Roberts, E; Verner-Jeffreys, D; Thompson, F

    2012-01-01

    Disposal of fish by-products in the European Community must comply with Regulation (EC) No 1069/2009 which categorizes animal by-products according to risk, and specifies methods of disposal of by-products according to that risk. There is provision under the regulation for composting or ensiling to be used for by-products from aquatic animals. Biosecurity considerations require knowledge of the parameters of time and temperature, or time and pH, required to inactivate any fish pathogens that may be present. To provide those data, we undertook laboratory studies on the inactivation of a number of fish pathogenic viruses and bacteria at 60?°C, pH?4.0 and pH?12.0 as a preliminary to conducting subsequent trials with the most resistant viruses and bacteria in fish tissues. The most resistant bacterium to 60?°C, pH?4.0 as well as pH?12.0 was Lactococcus garvieae. Its concentration was reduced to the level of sensitivity of the test after 24-48?h exposure to 60?°C, but it survived for at least 7?days at pH?4.0 and 14?days at pH?12.0. The most resistant virus to 60 °C was infectious pancreatic necrosis virus, and to pH?12.0 was infectious salmon anaemia virus. The majority of the viruses tested survived exposure to pH?4.0 for up to 28?days. The results suggest that the process of acid ensiling alone is not an effective method for the inactivation of many viral and bacterial pathogens, and fish by-products would need further treatment by a method approved under the regulation following ensiling, whereas alkaline or heat treatment are likely to provide an increased degree of biosecurity for on-farm processing of mortalities. PMID:22168455

  1. Canine Enteric Coronaviruses: Emerging Viral Pathogens with Distinct Recombinant Spike Proteins

    PubMed Central

    Licitra, Beth N.; Duhamel, Gerald E.; Whittaker, Gary R.

    2014-01-01

    Canine enteric coronavirus (CCoV) is an alphacoronavirus infecting dogs that is closely related to enteric coronaviruses of cats and pigs. While CCoV has traditionally caused mild gastro-intestinal clinical signs, there are increasing reports of lethal CCoV infections in dogs, with evidence of both gastrointestinal and systemic viral dissemination. Consequently, CCoV is now considered to be an emerging infectious disease of dogs. In addition to the two known serotypes of CCoV, novel recombinant variants of CCoV have been found containing spike protein N-terminal domains (NTDs) that are closely related to those of feline and porcine strains. The increase in disease severity in dogs and the emergence of novel CCoVs can be attributed to the high level of recombination within the spike gene that can occur during infection by more than one CCoV type in the same host. PMID:25153347

  2. Plant responses against invasive nucleic acids: RNA silencing and its suppression by plant viral pathogens

    PubMed Central

    Alvarado, Veria; Scholthof, Herman B.

    2010-01-01

    RNA silencing is a common strategy shared by eukaryotic organisms to regulate gene expression, and also operates as a defense mechanism against invasive nucleic acids such as viral transcripts. The silencing pathway is quite sophisticated in higher eukaryotes but the distinct steps and nature of effector complexes vary between and even within species. To counteract this defense mechanism viruses have evolved the ability to encode proteins that suppress silencing to protect their genomes from degradation. This review focuses on our current understanding of how individual components of the plant RNA silencing mechanism are directed against viruses, and how in turn virus-encoded suppressors target one or more key events in the silencing cascade. PMID:19524057

  3. A host-restricted viral vector for antigen-specific immunization against Lyme disease pathogen.

    PubMed

    Xiao, Sa; Kumar, Manish; Yang, Xiuli; Akkoyunlu, Mustafa; Collins, Peter L; Samal, Siba K; Pal, Utpal

    2011-07-18

    Newcastle disease virus (NDV) is an avian virus that is attenuated in primates and is a potential vaccine vector for human use. We evaluated NDV as a vector for expressing selected antigens of the Lyme disease pathogen Borrelia burgdorferi. A series of recombinant NDVs were generated that expressed intracellular or extracellular forms of two B. burgdorferi antigens: namely, the basic membrane protein A (BmpA) and the outer surface protein C (OspC). Expression of the intracellular and extracellular forms of these antigens was confirmed in cultured chicken cells. C3H or Balb/C mice that were immunized intranasally with the NDV vectors mounted vigorous serum antibody responses against the NDV vector, but failed to mount a robust response against either the intracellular or extracellular forms of BmpA or OspC. By contrast, a single immunization of hamsters with the NDV vectors via the intranasal, intramuscular, or intraperitoneal route resulted in rapid and rigorous antibody responses against the intracellular or extracellular forms of BmpA and OspC. When groups of hamsters were separately inoculated with various NDV vectors and challenged with B. burgdorferi (10(8)cells/animal), immunization with vector expressing either intracellular or extracellular BmpA was associated with a significant reduction of the pathogen load in the joints. Taken together, our studies highlighted the importance of NDV as vaccine vector that can be used for simple yet effective immunization of hosts against bacterial infections including Lyme disease. PMID:21600949

  4. A host-restricted viral vector for antigen-specific immunization against Lyme disease pathogen

    PubMed Central

    Xiao, Sa; Kumar, Manish; Yang, Xiuli; Akkoyunlu, Mustafa; Collins, Peter L.; Samal, Siba K.; Pal, Utpal

    2011-01-01

    Newcastle disease virus (NDV) is an avian virus that is attenuated in primates and is a potential vaccine vector for human use. We evaluated NDV as a vector for expressing selected antigens of the Lyme disease pathogen Borrelia burgdorferi. A series of recombinant NDVs were generated that expressed intracellular or extracellular forms of two Borrelia burgdorferi antigens: namely, the basic membrane protein A (BmpA) and the outer surface protein C (OspC). Expression of the intracellular and extracellular forms of these antigens was confirmed in cultured chicken cells. C3H or Balb/C mice that were immunized intranasally with the NDV vectors mounted vigorous serum antibody responses against the NDV vector, but failed to mount a robust response against either the intracellular or extracellular forms of BmpA or OspC. In contrast, a single immunization of hamsters with the NDV vectors via the intranasal, intramuscular, or intraperitoneal route resulted in rapid and rigorous antibody responses against the intracellular or extracellular forms of BmpA and OspC. When groups of hamsters were separately inoculated with various NDV vectors and challenged with B. burgdorferi (108 cells/animal), immunization with vector expressing either intracellular or extracellular BmpA was associated with a significant reduction of the pathogen load in the joints. Taken together, our studies highlighted the importance of NDV as vaccine vector that can be used for simple yet effective immunization of hosts against bacterial infections including Lyme disease. PMID:21600949

  5. Source identification of bacterial and viral pathogens and their survival/fading in the process of wastewater treatment, reclamation, and environmental reuse.

    PubMed

    Zhou, Jinhong; Wang, Xiaochang C; Ji, Zheng; Xu, Limei; Yu, Zhenzhen

    2015-01-01

    Pathogenic safety is drawing wide concern in water reclamation and reuse. In order to elucidate survive/fade of pathogens during the processes of wastewater treatment and reclamation, general indicators (fecal coliform and Escherichia coli), pathogenic bacteria (Salmonella and Shigella) and viruses (enterovirus, rotavirus and norovirus) were investigated in an A(2)O-MBR system. Attention was paid to their strengths from different sources, at various stages of the treatment, and in the product water. According to findings, black water was the main source for pathogens-at least 1-2-log higher in concentration than those from other sources. The preliminary treatment of wastewater by fine screens could bring about 0.2-0.4-log removal for almost all pathogens. The biological treatment units achieved almost identical removal (1.3-1.7-log) for bacteria and viruses. However, subsequent treatment in the membrane bioreactor showed varied removal for fecal coliform (4.7-log), E. coli (2.6-log) and the other pathogens (0.7-1.0-log), indicating that a high reduction of indicator bacteria may not imply equivalent removal of bacterial and viral pathogens. Chlorination was proved to be effective for eliminating all pathogens. In the artificial lake where the product water was stored, fecal coliform was not detected during the study period, but E. coli and pathogens were frequently detected, indicating that these bacterial and viral pathogens may be originating from non-fecal sources. On sunny summer days, the lake water could be bacteria-free due to sunlight radiation, but viruses were still detectable. Therefore, secondary disinfection may have to be adopted when the reclaimed water stored in such an open reservoir is supplied for strict reuse purposes. PMID:25374337

  6. Human Monoclonal Antibodies Against a Plethora of Viral Pathogens From Single Combinatorial Libraries

    NASA Astrophysics Data System (ADS)

    Williamson, R. Anthony; Burioni, Roberto; Sanna, Pietro P.; Partridge, Lynda J.; Barbas, Carlos F., III; Burton, Dennis R.

    1993-05-01

    Conventional antibody generation usually requires active immunization with antigen immediately prior to the preparation procedure. Combinatorial antibody library technology offers the possibility of cloning a range of antibody specificities at a single point in time and then accessing these specificities at will. Here we show that human monoclonal antibody Fab fragments against a plethora of infectious agents can be readily derived from a single library. Further examination of a number of libraries shows that whenever antibody against a pathogen can be detected in the serum of the donor, then specific antibodies can be derived from the corresponding library. We describe the generation of human Fab fragments against herpes simplex virus types 1 and 2, human cytomegalovirus, varicella zoster virus, rubella, human immunodeficiency virus type 1, and respiratory syncytial virus. The antibodies are shown to be highly specific and a number are effective in neutralizing virus in vitro.

  7. Impact of Piriformospora indica on tomato growth and on interaction with fungal and viral pathogens.

    PubMed

    Fakhro, Ahmad; Andrade-Linares, Diana Rocío; von Bargen, Susanne; Bandte, Martina; Büttner, Carmen; Grosch, Rita; Schwarz, Dietmar; Franken, Philipp

    2010-03-01

    Piriformospora indica is a root endophytic fungus with plant-promoting properties in numerous plant species and induces resistance against root and shoot pathogens in barley, wheat, and Arabidopsis. A study over several years showed that the endophyte P. indica colonised the roots of the most consumed vegetable crop tomato. P. indica improved the growth of tomato resulting in increased biomass of leaves by up to 20%. Limitation of disease severity caused by Verticillium dahliae by more than 30% was observed on tomato plants colonised by the endophyte. Further experiments were carried out in hydroponic cultures which are commonly used for the indoor production of tomatoes in central Europe. After adaptation of inoculation techniques (inoculum density, plant stage), it was shown that P. indica influences the concentration of Pepino mosaic virus in tomato shoots. The outcome of the interaction seems to be affected by light intensity. Most importantly, the endophyte increases tomato fruit biomass in hydroponic culture concerning fresh weight (up to 100%) and dry matter content (up to 20%). Hence, P. indica represents a suitable growth promoting endophyte for tomato which can be applied in production systems of this important vegetable plant not only in soil, but also in hydroponic cultures. PMID:19789897

  8. Interferometric biosensing platform for multiplexed digital detection of viral pathogens and biomarkers

    NASA Astrophysics Data System (ADS)

    Daaboul, George

    Label-free optical biosensors have been established as proven tools for monitoring specific biomolecular interactions. However, compact and robust embodiments of such instruments have yet to be introduced in order to provide sensitive, quantitative, and high-throughput biosensing for low-cost research and clinical applications. Here we present the interferometric reflectance-imaging sensor (IRIS). IRIS allows sensitive label free analysis using an inexpensive and durable multi-color LED illumination source on a silicon based surface. IRIS monitors biomolecular interaction through measurement of biomass addition to the sensor's surface. We demonstrate the capability of this system to dynamically monitor antigen---antibody interactions with a noise floor of 5.2 pg/mm 2 and DNA single mismatch detection under isothermal melting conditions in an array format. Ensemble detection of binding events using IRIS did not provide the sensitivity needed for detection of infectious disease and biomarkers at clinically relevant concentrations. Therefore, a new approach was adapted to the IRIS platform that allowed the detection and identification of individual nanoparticles on the sensor's surface. The new detection method was termed single-particle IRIS (SP-IRIS). We developed two detection modalities for SP-IRIS. The first modality is when the target is a nanoparticle such as a virus. We verified that SP-IRIS can accurately detect and size individual viral particles. Then we demonstrated that single nanoparticle counting and sizing methodology on SP-IRIS leads to a specific and sensitive virus sensor that can be multiplexed. Finally, we developed an assay for the detection of Ebola and Marburg. A detection limit of 3 x 103 PFU/ml was demonstrated for vesicular stomatitis virus (VSV) pseudotyped with Ebola or Marburg virus glycoprotein. We have demonstrated that virus detection can be done in human whole blood directly without the need for sample preparation. The second modality of SP-IRIS we developed was single molecule counting of biomarkers utilizing a sandwich assay with detection probes labeled with gold nanoparticles. We demonstrated the use of single molecule counting in a nucleic acid assay for melanoma biomarker detection. We showed that a single molecule counting assay can lead to detection limits in the attomolar range. The improved sensitivity of IRIS utilizing single nanoparticle detection holds promise for a simple and low-cost technology for rapid virus detection and multiplexed molecular screening for clinical applications.

  9. Optofluidic device monitoring and fluid dynamics simulation for the spread of viral pathogens in a livestock environment.

    PubMed

    Kwon, Hyuck-Jin; Lee, Chang-Hee; Choi, Eun-Jin; Song, Jae-Young; Heinze, Brian C; Yoon, Jeong-Yeol

    2010-11-01

    Rapid monitoring of the spreads of porcine reproductive and respiratory syndrome virus (PRRSV) was attempted using samples collected from nasal swabs of pigs and air samplers within an experimental swine building. An optofluidic device containing liquid-core waveguides was used to detect forward Mie light scattering caused by the agglutination of anti-PRRSV-conjugated submicron particles, with enhanced sensitivity, signal reproducibility, and reusability (reusable up to 75 assays). These results were compared with reverse transcription polymerase chain reaction (RT-PCR) assays (35 cycles) and showed excellent agreements to them. Each assay took less than 10 min including all necessary sample pre-processing, while the RT-PCR assays took up to 4 h including sample pre-processing and gel imaging for PCR products. A 3-D computational fluid dynamics (CFD) simulation was utilized to track the transport and distribution of PRRSV (from the mouths of pigs to the exhaust fans) within a swine building, and compared with the readings from an optofluidic device. Simulation results corresponded well with the experimental data, validating our 3-D CFD model for the spread of viral pathogens in a livestock environment. The developed optofluidic device and 3-D CFD model can serve as a good model for monitoring the spread of influenza A (swine and avian) within animal and human environments. PMID:20886169

  10. Direct and indirect effects of viral pathogens and the environment on invasive grass fecundity in Pacific Coast grasslands

    Microsoft Academic Search

    Eric W. Seabloom; Elizabeth T. Borer; Anna Jolles; Charles E. Mitchell

    2009-01-01

    Summary 1. Pathogens can have strong effects on their hosts and can be important determinants of biological invasions. In natural systems, host-pathogen interactions may be mediated by direct environmental effects on pathogen communities and host fitness. 2. While environmental mediation of host-pathogen interactions has been investigated experimentally and at single sites, there have been few studies tracking pathogen effects on

  11. Role of ribonuclease L in viral pathogen-associated molecular pattern/influenza virus and cigarette smoke-induced inflammation and remodeling.

    PubMed

    Zhou, Yang; Kang, Min-Jong; Jha, Babal Kant; Silverman, Robert H; Lee, Chun Geun; Elias, Jack A

    2013-09-01

    Interactions between cigarette smoke (CS) exposure and viral infection play an important role(s) in the pathogenesis of chronic obstructive pulmonary disease and a variety of other disorders. A variety of lines of evidence suggest that this interaction induces exaggerated inflammatory, cytokine, and tissue remodeling responses. We hypothesized that the 2'-5' oligoadenylate synthetase (OAS)/RNase L system, an innate immune antiviral pathway, plays an important role in the pathogenesis of these exaggerated responses. To test this hypothesis, we characterize the activation of 2'-5' OAS in lungs from mice exposed to CS and viral pathogen-associated molecular patterns (PAMPs)/live virus, alone and in combination. We also evaluated the inflammatory and remodeling responses induced by CS and virus/viral PAMPs in lungs from RNase L null and wild-type mice. These studies demonstrate that CS and viral PAMPs/live virus interact in a synergistic manner to stimulate the production of select OAS moieties. They also demonstrate that RNase L plays a critical role in the pathogenesis of the exaggerated inflammatory, fibrotic, emphysematous, apoptotic, TGF-?1, and type I IFN responses induced by CS plus virus/viral PAMP in combination. These studies demonstrate that CS is an important regulator of antiviral innate immunity, highlight novel roles of RNase L in CS plus virus induced inflammation, tissue remodeling, apoptosis, and cytokine elaboration and highlight pathways that may be operative in chronic obstructive pulmonary disease and mechanistically related disorders. PMID:23913960

  12. Pinellia ternata agglutinin expression in chloroplasts confers broad spectrum resistance against aphid, whitefly, Lepidopteran insects, bacterial and viral pathogens

    PubMed Central

    Jin, Shuangxia; Zhang, Xianlong; Daniell, Henry

    2012-01-01

    Summary Broad spectrum protection against different insects and pathogens requires multigene engineering. However, such broad spectrum protection against biotic stress is provided by a single protein in some medicinal plants. Therefore, tobacco chloroplasts were transformed with the agglutinin gene from Pinellia ternata (pta), a widely cultivated Chinese medicinal herb. Pinellia ternata agglutinin (PTA) was expressed up to 9.2% of total soluble protein in mature leaves. Purified PTA showed similar hemagglutination activity as snowdrop lectin. Artificial diet with purified PTA from transplastomic plants showed marked and broad insecticidal activity. In planta bioassays conducted with T0 or T1 generation PTA lines showed that the growth of aphid Myzus persicae (Sulzer) was reduced by 89%–92% when compared with untransformed (UT) plants. Similarly, the larval survival and total population of whitefly (Bemisia tabaci) on transplastomic lines were reduced by 91%–93% when compared with UT plants. This is indeed the first report of lectin controlling whitefly infestation. When transplastomic PTA leaves were fed to corn earworm (Helicoverpa zea), tobacco budworm (Heliothis virescens) or the beet armyworm (spodoptera exigua), 100% mortality was observed against all these three insects. In planta bioassays revealed Erwinia population to be 10 000-fold higher in control than in PTA lines. Similar results were observed with tobacco mosaic virus (TMV) challenge. Therefore, broad spectrum resistance to homopteran (sap-sucking), Lepidopteran insects as well as anti-bacterial or anti-viral activity observed in PTA lines provides a new option to engineer protection against biotic stress by hyper-expression of an unique protein that is naturally present in a medicinal plant. PMID:22077160

  13. Viral Replication Rate Regulates Clinical Outcome and CD8 T Cell Responses during Highly Pathogenic H5N1 Influenza Virus Infection in Mice

    PubMed Central

    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-? 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

  14. Ac23, an Envelope Fusion Protein Homolog in the Baculovirus Autographa californica Multicapsid Nucleopolyhedrovirus, Is a Viral Pathogenicity Factor

    Microsoft Academic Search

    Oliver Y. Lung; Marilyn Cruz-Alvarez; Gary W. Blissard

    2003-01-01

    Viral envelope fusion proteins are important structural proteins that mediate viral entry and may affect or determine the host range of a virus. The acquisition, exchange, and evolution of such envelope proteins may dramatically affect the success and evolutionary divergence of viruses. In the family Baculoviridae, two very different envelope fusion proteins have been identified. Budded virions of group I

  15. Viral Infections

    Microsoft Academic Search

    Coley B. Duncan; Ann R. Falsey

    Although influenza remains indisputably the most significant viral pathogen in adults, other viruses such as respiratory syncytial\\u000a virus, parainfluenza viruses, and human metapneumovirus are now recognized as significant pathogens in older populations.\\u000a \\u000a Oseltamivir and zanamivir are antiviral agents that are effective for the treatment and prophylaxis of influenza A and B.\\u000a For treatment and for optimal effect, therapy should be

  16. 1918 Influenza virus hemagglutinin (HA) and the viral RNA polymerase complex enhance viral pathogenicity, but only HA induces aberrant host responses in mice.

    PubMed

    Watanabe, Tokiko; Tisoncik-Go, Jennifer; Tchitchek, Nicolas; Watanabe, Shinji; Benecke, Arndt G; Katze, Michael G; Kawaoka, Yoshihiro

    2013-05-01

    The 1918 pandemic influenza virus was the most devastating infectious agent in human history, causing fatal pneumonia and an estimated 20 to 50 million deaths worldwide. Previous studies indicated a prominent role of the hemagglutinin (HA) gene in efficient replication and high virulence of the 1918 virus in mice. It is, however, still unclear whether the high replication ability or the 1918 influenza virus HA gene is required for 1918 virus to exhibit high virulence in mice. Here, we examined the biological properties of reassortant viruses between the 1918 virus and a contemporary human H1N1 virus (A/Kawasaki/173/2001 [K173]) in a mouse model. In addition to the 1918 influenza virus HA, we demonstrated the role of the viral RNA replication complex in efficient replication of viruses in mouse lungs, whereas only the HA gene is responsible for lethality in mice. Global gene expression profiling of infected mouse lungs revealed that the 1918 influenza virus HA was sufficient to induce transcriptional changes similar to those induced by the 1918 virus, despite difference in lymphocyte gene expression. Increased expression of genes associated with the acute-phase response and the protein ubiquitination pathway were enriched during infections with the 1918 and 1918HA/K173 viruses, whereas reassortant viruses bearing the 1918 viral RNA polymerase complex induced transcriptional changes similar to those seen with the K173 virus. Taken together, these data suggest that HA and the viral RNA polymerase complex are critical determinants of Spanish influenza pathogenesis, but only HA, and not the viral RNA polymerase complex and NP, is responsible for extreme host responses observed in mice infected with the 1918 influenza virus. PMID:23449804

  17. 1918 Influenza Virus Hemagglutinin (HA) and the Viral RNA Polymerase Complex Enhance Viral Pathogenicity, but Only HA Induces Aberrant Host Responses in Mice

    PubMed Central

    Tisoncik-Go, Jennifer; Tchitchek, Nicolas; Watanabe, Shinji; Benecke, Arndt G.; Katze, Michael G.

    2013-01-01

    The 1918 pandemic influenza virus was the most devastating infectious agent in human history, causing fatal pneumonia and an estimated 20 to 50 million deaths worldwide. Previous studies indicated a prominent role of the hemagglutinin (HA) gene in efficient replication and high virulence of the 1918 virus in mice. It is, however, still unclear whether the high replication ability or the 1918 influenza virus HA gene is required for 1918 virus to exhibit high virulence in mice. Here, we examined the biological properties of reassortant viruses between the 1918 virus and a contemporary human H1N1 virus (A/Kawasaki/173/2001 [K173]) in a mouse model. In addition to the 1918 influenza virus HA, we demonstrated the role of the viral RNA replication complex in efficient replication of viruses in mouse lungs, whereas only the HA gene is responsible for lethality in mice. Global gene expression profiling of infected mouse lungs revealed that the 1918 influenza virus HA was sufficient to induce transcriptional changes similar to those induced by the 1918 virus, despite difference in lymphocyte gene expression. Increased expression of genes associated with the acute-phase response and the protein ubiquitination pathway were enriched during infections with the 1918 and 1918HA/K173 viruses, whereas reassortant viruses bearing the 1918 viral RNA polymerase complex induced transcriptional changes similar to those seen with the K173 virus. Taken together, these data suggest that HA and the viral RNA polymerase complex are critical determinants of Spanish influenza pathogenesis, but only HA, and not the viral RNA polymerase complex and NP, is responsible for extreme host responses observed in mice infected with the 1918 influenza virus. PMID:23449804

  18. The role of amphibian antimicrobial peptides in protection of amphibians from pathogens linked to global amphibian declines

    Microsoft Academic Search

    Louise A. Rollins-Smith

    2009-01-01

    Amphibian species have experienced population declines and extinctions worldwide that are unprecedented in recent history. Many of these recent declines have been linked to a pathogenic skin fungus, Batrachochytrium dendrobatidis, or to iridoviruses of the genus Ranavirus. One of the first lines of defense against pathogens that enter by way of the skin are antimicrobial peptides synthesized and stored in

  19. A reverse genetics system for the Great Lakes strain of viral hemorrhagic septicemia virus: the NV gene is required for pathogenicity.

    PubMed

    Ammayappan, Arun; Kurath, Gael; Thompson, Tarin M; Vakharia, Vikram N

    2011-08-01

    Viral hemorrhagic septicemia virus (VHSV), belonging to the genus Novirhabdovirus in the family of Rhabdoviridae, causes a highly contagious disease of fresh and saltwater fish worldwide. Recently, a novel genotype of VHSV, designated IVb, has invaded the Great Lakes in North America, causing large-scale epidemics in wild fish. An efficient reverse genetics system was developed to generate a recombinant VHSV of genotype IVb from cloned cDNA. The recombinant VHSV (rVHSV) was comparable to the parental wild-type strain both in vitro and in vivo, causing high mortality in yellow perch (Perca flavescens). A modified recombinant VHSV was generated in which the NV gene was substituted with an enhanced green fluorescent protein gene (rVHSV-?NV-EGFP), and another recombinant was made by inserting the EGFP gene into the full-length viral clone between the P and M genes (rVHSV-EGFP). The in vitro replication kinetics of rVHSV-EGFP was similar to rVHSV; however, the rVHSV-?NV-EGFP grew 2 logs lower. In yellow perch challenges, wtVHSV and rVHSV induced 82-100% cumulative per cent mortality (CPM), respectively, whereas rVHSV-EGFP produced 62% CPM and rVHSV-?NV-EGFP caused only 15% CPM. No reversion of mutation was detected in the recovered viruses and the recombinant viruses stably maintained the foreign gene after several passages. These results indicate that the NV gene of VHSV is not essential for viral replication in vitro and in vivo, but it plays an important role in viral replication efficiency and pathogenicity. This system will facilitate studies of VHSV replication, virulence, and production of viral vectored vaccines. PMID:20936318

  20. A reverse genetics system for the Great Lakes strain of viral hemorrhagic septicemia virus: the NV gene is required for pathogenicity

    USGS Publications Warehouse

    Ammayappan, Arun; Kurath, Gael; Thompson, Tarin M.; Vakharia, Vikram N.

    2011-01-01

    Viral hemorrhagic septicemia virus (VHSV), belonging to the genus Novirhabdovirus in the family of Rhabdoviridae, causes a highly contagious disease of fresh and saltwater fish worldwide. Recently, a novel genotype of VHSV, designated IVb, has invaded the Great Lakes in North America, causing large-scale epidemics in wild fish. An efficient reverse genetics system was developed to generate a recombinant VHSV of genotype IVb from cloned cDNA. The recombinant VHSV (rVHSV) was comparable to the parental wild-type strain both in vitro and in vivo, causing high mortality in yellow perch (Perca flavescens). A modified recombinant VHSV was generated in which the NV gene was substituted with an enhanced green fluorescent protein gene (rVHSV-?NV-EGFP), and another recombinant was made by inserting the EGFP gene into the full-length viral clone between the P and M genes (rVHSV-EGFP). The in vitro replication kinetics of rVHSV-EGFP was similar to rVHSV; however, the rVHSV-?NV-EGFP grew 2 logs lower. In yellow perch challenges, wtVHSV and rVHSV induced 82-100% cumulative per cent mortality (CPM), respectively, whereas rVHSV-EGFP produced 62% CPM and rVHSV-?NV-EGFP caused only 15% CPM. No reversion of mutation was detected in the recovered viruses and the recombinant viruses stably maintained the foreign gene after several passages. These results indicate that the NV gene of VHSV is not essential for viral replication in vitro and in vivo, but it plays an important role in viral replication efficiency and pathogenicity. This system will facilitate studies of VHSV replication, virulence, and production of viral vectored vaccines.

  1. Co-infection by alveolate parasites and frog virus 3-like ranavirus during an amphibian larval mortality event in Florida, USA.

    PubMed

    Landsberg, Jan H; Kiryu, Yasunari; Tabuchi, Maki; Waltzek, Thomas B; Enge, Kevin M; Reintjes-Tolen, Sarah; Preston, Asa; Pessier, Allan P

    2013-07-22

    A multispecies amphibian larval mortality event, primarily affecting American bullfrogs Lithobates catesbeianus, was investigated during April 2011 at the Mike Roess Gold Head Branch State Park, Clay County, Florida, USA. Freshly dead and moribund tadpoles had hemorrhagic lesions around the vent and on the ventral body surface, with some exhibiting a swollen abdomen. Bullfrogs (100%), southern leopard frogs L. sphenocephalus (33.3%), and gopher frogs L. capito (100%) were infected by alveolate parasites. The intensity of infection in bullfrog livers was high. Tadpoles were evaluated for frog virus 3 (FV3) by histology and PCR. For those southern leopard frog tadpoles (n = 2) whose livers had not been obscured by alveolate spore infection, neither a pathologic response nor intracytoplasmic inclusions typically associated with clinical infections of FV3-like ranavirus were noted. Sequencing of a portion (496 bp) of the viral major capsid protein gene confirmed FV3-like virus in bullfrogs (n = 1, plus n = 6 pooled) and southern leopard frogs (n = 1, plus n = 4 pooled). In July 2011, young-of-the-year bullfrog tadpoles (n = 7) were negative for alveolate parasites, but 1 gopher frog tadpole was positive. To our knowledge, this is the first confirmed mortality event for amphibians in Florida associated with FV3-like virus, but the extent to which the virus played a primary role is uncertain. Larval mortality was most likely caused by a combination of alveolate parasite infections, FV3-like ranavirus, and undetermined etiological factors. PMID:23872853

  2. Variation in viral shedding patterns between different wild bird species infected experimentally with low-pathogenicity avian influenza viruses that originated from wild birds.

    PubMed

    Costa, Taiana P; Brown, Justin D; Howerth, Elizabeth W; Stallknecht, David E

    2011-04-01

    The prevalence of infection with avian influenza (AI) virus varies significantly between taxonomic Orders and even between species within the same Order. The current understanding of AI infection and virus shedding parameters in wild birds is limited and largely based on trials conducted in mallards (Anas platyrhynchos). The objective of the present study was to provide experimental data to examine species-related differences in susceptibility and viral shedding associated with wild bird-origin low-pathogenicity avian influenza (LPAI) viruses in multiple duck species and gulls. Thus mallards, redheads (Aythya americana), wood ducks (Aix sponsa), and laughing gulls (Leucophaeus atricilla) were inoculated experimentally with three wild mallard-origin LPAI viruses representing multiple subtypes. Variation in susceptibility and patterns of viral shedding associated with LPAI virus infection was evident between the duck and gull species. Consistent with the literature, mallards excreted virus predominantly via the gastrointestinal tract. In wood ducks, redheads, and laughing gulls, AI virus was detected more often in oropharyngeal swabs than cloacal swabs. The results of this study suggest that LPAI shedding varies between taxonomically related avian species. Such differences may be important for understanding the potential role of individual species in the transmission and maintenance of LPAI viruses and may have implications for improving sampling strategies for LPAI detection. Additional comparative studies, which include LPAI viruses originating from non-mallard species, are necessary to further characterize these infections in wild avian species other than mallards and provide a mechanism to explain these differences in viral excretion. PMID:21500030

  3. 3 ``Ranaviruses: An emerging threat to ectothermic vertebrates'' Report of the 4 First International Symposium on Ranaviruses, Minneapolis MN July 8, 2011

    E-print Network

    Gray, Matthew

    1 2 Review 3 ``Ranaviruses: An emerging threat to ectothermic vertebrates'' Report of the 4 First to the global biodiversity of ectothermic ver- 26tebrates was addressed by 23 scientists from nine countries fish, amphibian and reptilian species. Thus, RVs 45 are an emerging threat to ectothermic vertebrates

  4. Distribution of an Invasive Aquatic Pathogen (Viral Hemorrhagic Septicemia Virus) in the Great Lakes and Its Relationship to Shipping

    Microsoft Academic Search

    Mark B. Bain; Emily R. Cornwell; Kristine M. Hope; Geofrey E. Eckerlin; Rufina N. Casey; Geoffrey H. Groocock; Rodman G. Getchell; Paul R. Bowser; James R. Winton; William N. Batts; Allegra Cangelosi; James W. Casey; Justin Brown

    2010-01-01

    Viral hemorrhagic septicemia virus (VHSV) is a rhabdovirus found in fish from oceans of the northern hemisphere and freshwaters of Europe. It has caused extensive losses of cultured and wild fish and has become established in the North American Great Lakes. Large die-offs of wild fish in the Great Lakes due to VHSV have alarmed the public and provoked government

  5. Applications of in vivo imaging in the evaluation of the pathophysiology of viral and bacterial infections and in development of countermeasures to BSL3/4 pathogens.

    PubMed

    Bocan, Thomas M; Panchal, Rekha G; Bavari, Sina

    2015-02-01

    While preclinical and clinical imaging have been applied to drug discovery/development and characterization of disease pathology, few examples exist where imaging has been used to evaluate infectious agents or countermeasures to biosafety level (BSL)3/4 threat agents. Viruses engineered with reporter constructs, i.e., enzymes and receptors, which are amenable to detection by positron emission tomography (PET), single photon emission tomography (SPECT), or magnetic resonance imaging (MRI) have been used to evaluate the biodistribution of viruses containing specific therapeutic or gene transfer payloads. Bioluminescence and nuclear approaches involving engineered reporters, direct labeling of bacteria with radiotracers, or tracking bacteria through their constitutively expressed thymidine kinase have been utilized to characterize viral and bacterial pathogens post-infection. Most PET, SPECT, CT, or MRI approaches have focused on evaluating host responses to the pathogens such as inflammation, brain neurochemistry, and structural changes and on assessing the biodistribution of radiolabeled drugs. Imaging has the potential when applied preclinically to the development of countermeasures against BSL3/4 threat agents to address the following: (1) presence, biodistribution, and time course of infection in the presence or absence of drug; (2) binding of the therapeutic to the target; and (3) expression of a pharmacologic effect either related to drug mechanism, efficacy, or safety. Preclinical imaging could potentially provide real-time dynamic tools to characterize the pathogen and animal model and for developing countermeasures under the U.S. FDA Animal Rule provision with high confidence of success and clinical benefit. PMID:25008802

  6. Fate and Transport of Zoonotic Bacterial, Viral, and Parasitic Pathogens During Swine Manure Treatment, Storage, and Land Application

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Generally, the public is always somewhat aware of foodborne and other zoonotic pathogens; however, recent illnesses traced to produce and the emergence of another avian influenza virus have increased the scrutiny on all areas of food production. The Council for Agricultural Science and Technology h...

  7. Major capsid protein gene sequence analysis of the Santee-Cooper ranaviruses DFV, GV6, and LMBV.

    PubMed

    Ohlemeyer, S; Holopainen, R; Tapiovaara, H; Bergmann, S M; Schütze, H

    2011-10-01

    The Santee-Cooper ranaviruses doctor fish virus (DFV), guppy virus 6 (GV6), and largemouth bass virus (LMBV) are members of the genus Ranavirus within the family Iridoviridae. The major capsid protein (MCP) is a main structural protein of iridoviruses and supports the differentiation and classification of ranaviruses. Presently the complete sequence of the MCP gene is known for most ranaviruses with the exception of the Santee-Cooper ranaviruses. In the present study, the complete nucleotide sequence of the MCP gene of DFV, GV6, and LMBV was determined. DFV and GV6 are identical within the MCP gene sequence. The identity compared to the corresponding sequence in LMBV amounts to 99.21%. The MCP gene of DFV, GV6, and LMBV exhibits only approximately 78% identity compared to the respective gene of other ranaviruses. Based on the sequence data obtained in the present study, a Rana MCP polymerase chain reaction (PCR) and subsequent restriction fragment length polymorphism (RFLP) analysis were developed to identify and differentiate ranaviruses, including DFV, GV6, and LMBV. PMID:22132498

  8. A multiplexed reverse transcriptase PCR assay for identification of viral respiratory pathogens at point-of-care

    SciTech Connect

    Letant, S E; .Ortiz, J I; Tammero, L; Birch, J M; Derlet, R W; Cohen, S; Manning, D; McBride, M T

    2007-04-11

    We have developed a nucleic acid-based assay that is rapid, sensitive, specific, and can be used for the simultaneous detection of 5 common human respiratory pathogens including influenza A, influenza B, parainfluenza type 1 and 3, respiratory syncytial virus, and adenovirus group B, C, and E. Typically, diagnosis on an un-extracted clinical sample can be provided in less than 3 hours, including sample collection, preparation, and processing, as well as data analysis. Such a multiplexed panel would enable rapid broad-spectrum pathogen testing on nasal swabs, and therefore allow implementation of infection control measures, and timely administration of antiviral therapies. This article presents a summary of the assay performance in terms of sensitivity and specificity. Limits of detection are provided for each targeted respiratory pathogen, and result comparisons are performed on clinical samples, our goal being to compare the sensitivity and specificity of the multiplexed assay to the combination of immunofluorescence and shell vial culture currently implemented at the UCDMC hospital. Overall, the use of the multiplexed RT-PCR assay reduced the rate of false negatives by 4% and reduced the rate of false positives by up to 10%. The assay correctly identified 99.3% of the clinical negatives, 97% of adenovirus, 95% of RSV, 92% of influenza B, and 77% of influenza A without any extraction performed on the clinical samples. The data also showed that extraction will be needed for parainfluenza virus, which was only identified correctly 24% of the time on un-extracted samples.

  9. The origin of the PB1 segment of swine influenza A virus subtype H1N2 determines viral pathogenicity in mice.

    PubMed

    Metreveli, Giorgi; Gao, Qinshan; Mena, Ignacio; Schmolke, Mirco; Berg, Mikael; Albrecht, Randy A; García-Sastre, Adolfo

    2014-08-01

    Swine appear to be a key species in the generation of novel human influenza pandemics. Previous pandemic viruses are postulated to have evolved in swine by reassortment of avian, human, and swine influenza viruses. The human pandemic influenza viruses that emerged in 1957 and 1968 as well as swine viruses circulating since 1998 encode PB1 segments derived from avian influenza viruses. Here we investigate the possible role in viral replication and virulence of the PB1 gene segments present in two swine H1N2 influenza A viruses, A/swine/Sweden/1021/2009(H1N2) (sw 1021) and A/swine/Sweden/9706/2010(H1N2) (sw 9706), where the sw 1021 virus has shown to be more pathogenic in mice. By using reverse genetics, we swapped the PB1 genes of these two viruses. Similar to the sw 9706 virus, chimeric sw 1021 virus carrying the sw 9706 PB1 gene was not virulent in mice. In contrast, replacement of the PB1 gene of the sw 9706 virus by that from sw 1021 virus resulted in increased pathogenicity. Our study demonstrated that differences in virulence of swine influenza virus subtype H1N2 are attributed at least in part to the PB1 segment. PMID:24726997

  10. Amphibian pathogens in Southeast Asian frog trade.

    PubMed

    Gilbert, Martin; Bickford, David; Clark, Leanne; Johnson, Arlyne; Joyner, Priscilla H; Ogg Keatts, Lucy; Khammavong, Kongsy; Nguy?n V?n, Long; Newton, Alisa; Seow, Tiffany P W; Roberton, Scott; Silithammavong, Soubanh; Singhalath, Sinpakhone; Yang, Angela; Seimon, Tracie A

    2012-12-01

    Amphibian trade is known to facilitate the geographic spread of pathogens. Here we assess the health of amphibians traded in Southeast Asia for food or as pets, focusing on Batrachochytrium dendrobatidis (Bd), ranavirus and general clinical condition. Samples were collected from 2,389 individual animals at 51 sites in Lao PDR, Cambodia, Vietnam and Singapore for Bd screening, and 74 animals in Cambodia and Vietnam for ranavirus screening. Bd was found in one frog (n = 347) in Cambodia and 13 in Singapore (n = 419). No Bd was found in Lao PDR (n = 1,126) or Vietnam (n = 497), and no ranavirus was found in Cambodia (n = 70) or Vietnam (n = 4). Mild to severe dermatological lesions were observed in all East Asian bullfrogs Hoplobatrachus rugolosus (n = 497) sampled in farms in Vietnam. Histologic lesions consistent with sepsis were found within the lesions of three frogs and bacterial sepsis in two (n = 4); one had Gram-negative bacilli and one had acid-fast organisms consistent with mycobacterium sp. These results confirm that Bd is currently rare in amphibian trade in Southeast Asia. The presence of Mycobacterium-associated disease in farmed H. rugolosus is a cause for concern, as it may have public health implications and indicates the need for improved biosecurity in amphibian farming and trade. PMID:23404036

  11. First Evidence of Amphibian Chytrid Fungus (Batrachochytrium dendrobatidis) and Ranavirus in Hong

    E-print Network

    Gray, Matthew

    First Evidence of Amphibian Chytrid Fungus (Batrachochytrium dendrobatidis) and Ranavirus in Hong Kong Amphibian Trade Jonathan E. Kolby1,2 *, Kristine M. Smith2 , Lee Berger1 , William B. Karesh2 of America, 3 Amphibian Disease Laboratory, Institute for Conservation Research, San Diego Zoo Global, San

  12. Comparative genomic analyses of frog virus 3, type species of the genus Ranavirus (family Iridoviridae)

    Microsoft Academic Search

    Wendy G. H Tan; Todd J Barkman; V Gregory Chinchar; Karim Essani

    2004-01-01

    Frog virus 3 (FV3) is the type species member of the genus Ranavirus (family Iridoviridae). To better understand the molecular mechanisms involved in the replication of FV3, including transcription of its highly methylated DNA genome, we have determined the complete nucleotide sequence of the FV3 genome. The FV3 genome is 105903 bp long excluding the terminal redundancy. The G +

  13. Studies on the inactivation of selected viral and bacterial fish pathogens at high pH for waste disposal purposes.

    PubMed

    Dixon, P F; Algoët, M; Bayley, A; Dodge, M; Joiner, C; Roberts, E

    2012-01-01

    This study investigated the use of alkaline hydrolysis at ambient temperature for inactivation of selected fish pathogens in fish tissues under conditions approximating those that are likely to be found in the aquaculture industry. Infectious salmon anaemia virus (ISAV) and Lactococcus garvieae have been determined in a previous study to be the most resistant virus and bacteria to pH 12 from a wide range of viruses and bacteria tested. They were spiked at high titres into fish extracts that were then treated with 1 m sodium hydroxide (NaOH). Viable L. garvieae was not detected in the treated fish extract after 1 h, and ISAV was not detected after 24-h exposure. Field mortalities of Atlantic salmon, Salmo salar L., caused by infectious pancreatic necrosis virus were treated by alkaline hydrolysis at ambient temperature. The macerated fish mortalities contained a high titre of virus (3.38 × 10? TCID?? g?¹) that was reduced to approximately 2.2 × 10³ TCID?? g?¹ after 24-h exposure to NaOH, and virus was not detected after exposure for 48 h. The results suggest that alkaline hydrolysis at ambient temperature has potential as a biosecure treatment method for fish by-products containing fish pathogens. PMID:22092262

  14. Development of FPV140 antigen-specific ELISA differentiating fowlpox virus isolates from all other viral pathogens of avian origin.

    PubMed

    Li, G; Hong, Q; Ren, Y; Lillehoj, H S; He, C; Ren, X

    2012-10-01

    The FPV140 gene encodes an envelope protein of fowlpox virus (FPV). In this study, the FPV140 gene of FPV Chinese isolate HH2008 was cloned and the comparison of its sequence with other FPV isolates showed it to be highly conserved across all FPV isolates. A recombinant plasmid pET-FPV140 carrying FPV140 gene was constructed and transformed into Escherichia coli. The optimal expression condition for the FPV140 gene was developed and purified FPV140 recombinant protein was used to produce rabbit polyclonal antibody. An indirect ELISA using this anti-FPV140 polyclonal antibody was capable of distinguishing avian FPV isolates from other common avian pathogens such as mycoplasma gallisepticum, infectious laryngotracheitis virus, avian influenza virus, infectious bursal disease virus, and avian infectious bronchitis virus. This ELISA will serve as a useful diagnostic tool for the detection of FPV in clinical samples. PMID:22991535

  15. Orally administered Lactobacillus rhamnosus modulates the respiratory immune response triggered by the viral pathogen-associated molecular pattern poly(I:C)

    PubMed Central

    2012-01-01

    Background Some studies have shown that probiotics, including Lactobacillus rhamnosus CRL1505, had the potential to beneficially modulate the outcome of certain bacterial and viral respiratory infections. However, these studies did not determine the mechanism(s) by which probiotics contribute to host defense against respiratory viruses. Results In this work we demonstrated that orally administered Lactobacillus rhamnosus CRL1505 (Lr1505) was able to increase the levels of IFN-?, IL-10 and IL-6 in the respiratory tract and the number of lung CD3+CD4+IFN-?+ T cells. To mimic the pro-inflammatory and physiopathological consecuences of RNA viral infections in the lung, we used an experimental model of lung inflammation based on the administration of the artificial viral pathogen-associated molecular pattern poly(I:C). Nasal administration of poly(I:C) to mice induced a marked impairment of lung function that was accompanied by the production of pro-inflammatory mediators and inflammatory cell recruitment into the airways. The preventive administration of Lr1505 reduced lung injuries and the production of TNF-?, IL-6, IL-8 and MCP-1 in the respiratory tract after the challenge with poly(I:C). Moreover, Lr1505 induced a significant increase in lung and serum IL-10. We also observed that Lr1505 was able to increase respiratory IFN-? levels and the number of lung CD3+CD4+IFN-?+ T cells after poly(I:C) challenge. Moreover, higher numbers of both CD103+ and CD11bhigh dendritic cells and increased expression of MHC-II, IL-12 and IFN-? in these cell populations were found in lungs of Lr1505-treated mice. Therefore, Lr1505 treatment would beneficially regulate the balance between pro-inflammatory mediators and IL-10, allowing an effective inflammatory response against infection and avoiding tissue damage. Conclusions Results showed that Lr1505 would induce a mobilization of cells from intestine and changes in cytokine profile that would be able to beneficially modulate the respiratory mucosal immunity. Although deeper studies are needed using challenges with respiratory viruses, the results in this study suggest that Lr1505, a potent inducer of antiviral cytokines, may be useful as a prophylactic agent to control respiratory virus infection. PMID:22989047

  16. BIOMARKERS OF VIRAL EXPOSURE

    EPA Science Inventory

    Viral and protozoan pathogens associated with raw sludge can cause encephalitis, gastroenteritis, hepatitis, myocarditis, and a number of other diseases. Raw sludge that has been treated to reduce these pathogens can be used for land application according to the regulations spec...

  17. Rescue of Foot-and-Mouth Disease Viruses That Are Pathogenic for Cattle from Preserved Viral RNA Samples

    PubMed Central

    Belsham, Graham J.; Jamal, Syed M.; Tjørnehøj, Kirsten; Bøtner, Anette

    2011-01-01

    Background Foot and mouth disease is an economically important disease of cloven-hoofed animals including cattle, sheep and pigs. It is caused by a picornavirus, foot-and-mouth disease virus (FMDV), which has a positive sense RNA genome which, when introduced into cells, can initiate virus replication. Principal Findings A system has been developed to rescue infectious FMDV from RNA preparations generated from clinical samples obtained under experimental conditions and then applied to samples collected in the “field”. Clinical samples from suspect cases of foot-and-mouth disease (FMD) were obtained from within Pakistan and Afghanistan. The samples were treated to preserve the RNA and then transported to National Veterinary Institute, Lindholm, Denmark. Following RNA extraction, FMDV RNA was quantified by real-time RT-PCR and samples containing significant levels of FMDV RNA were introduced into susceptible cells using electroporation. Progeny viruses were amplified in primary bovine thyroid cells and characterized using antigen ELISA and also by RT-PCR plus sequencing. FMD viruses of three different serotypes and multiple lineages have been successfully rescued from the RNA samples. Two of the rescued viruses (of serotype O and Asia 1) were inoculated into bull calves under high containment conditions. Acute clinical disease was observed in each case which spread rapidly from the inoculated calves to in-contact animals. Thus the rescued viruses were highly pathogenic. The availability of the rescued viruses enabled serotyping by antigen ELISA and facilitated genome sequencing. Conclusions The procedure described here should improve the characterization of FMDVs circulating in countries where the disease is endemic and thus enhance disease control globally. PMID:21298025

  18. Low detection of ranavirus DNA in wild postmetamorphic green frogs, Rana (Lithobates) clamitans, despite previous or concurrent tadpole mortality.

    PubMed

    Forzán, María J; Wood, John

    2013-10-01

    Ranavirus (Iridoviridae) infection is a significant cause of mortality in amphibians. Detection of infected individuals, particularly carriers, is necessary to prevent and control outbreaks. Recently, the use of toe clips to detect ranavirus infection through PCR was proposed as an alternative to the more frequently used lethal liver sampling in green frogs (Rana [Lithobates] clamitans). We attempted reevaluate the use of toe clips, evaluate the potential use of blood onto filter paper and hepatic fine needle aspirates (FNAs) as further alternatives, and explore the adequacy of using green frogs as a target-sampling species when searching for ranavirus infection in the wild. Samples were obtained from 190 postmetamorphic (?1-yr-old) green frogs from five ponds on Prince Edward Island (PEI), Canada. Three of the ponds had contemporary or recent tadpole mortalities due to Frog Virus 3 (FV3) ranavirus. PCR testing for ranavirus DNA was performed on 190 toe clips, 188 blood samples, 72 hepatic FNAs, and 72 liver tissue samples. Only two frogs were ranavirus-positive: liver and toe clip were positive in one, liver only was positive in the other; all blood and FNAs, including those from the two positive frogs, were negative. Results did not yield a definitive answer on the efficacy of testing each type of sample, but resemble what is found in salamanders infected with Ambystoma tigrinum (rana)virus. Findings indicate a low prevalence of FV3 in postmetamorphic green frogs on PEI (?2.78%) and suggest that green frogs are poor reservoirs (carriers) for the virus. PMID:24502715

  19. Detection of 11 Common Viral and Bacterial Pathogens Causing Community-Acquired Pneumonia or Sepsis in Asymptomatic Patients by Using a Multiplex Reverse Transcription-PCR Assay with Manual (Enzyme Hybridization) or Automated (Electronic Microarray) Detection?

    PubMed Central

    Kumar, Swati; Wang, Lihua; Fan, Jiang; Kraft, Andrea; Bose, Michael E.; Tiwari, Sagarika; Van Dyke, Meredith; Haigis, Robert; Luo, Tingquo; Ghosh, Madhushree; Tang, Huong; Haghnia, Marjan; Mather, Elizabeth L.; Weisburg, William G.; Henrickson, Kelly J.

    2008-01-01

    Community-acquired pneumonia (CAP) and sepsis are important causes of morbidity and mortality. We describe the development of two molecular assays for the detection of 11 common viral and bacterial agents of CAP and sepsis: influenza virus A, influenza virus B, respiratory syncytial virus A (RSV A), RSV B, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, Legionella micdadei, Bordetella pertussis, Staphylococcus aureus, and Streptococcus pneumoniae. Further, we report the prevalence of carriage of these pathogens in respiratory, skin, and serum specimens from 243 asymptomatic children and adults. The detection of pathogens was done using both a manual enzyme hybridization assay and an automated electronic microarray following reverse transcription and PCR amplification. The analytical sensitivities ranged between 0.01 and 100 50% tissue culture infective doses, cells, or CFU per ml for both detection methods. Analytical specificity testing demonstrated no significant cross-reactivity among 19 other common respiratory organisms. One hundred spiked “surrogate” clinical specimens were all correctly identified with 100% specificity (95% confidence interval, 100%). Overall, 28 (21.7%) of 129 nasopharyngeal specimens, 11 of 100 skin specimens, and 2 of 100 serum specimens from asymptomatic subjects tested positive for one or more pathogens, with S. pneumoniae and S. aureus giving 89% of the positive results. Our data suggest that asymptomatic carriage makes the use of molecular assays problematic for the detection of S. pneumoniae or S. aureus in upper respiratory tract secretions; however, the specimens tested showed virtually no carriage of the other nine viral and bacterial pathogens, and the detection of these pathogens should not be a significant diagnostic problem. In addition, slightly less sensitive molecular assays may have better correlation with clinical disease in the case of CAP. PMID:18650351

  20. Viruses and viral proteins

    PubMed Central

    Verdaguer, Nuria; Ferrero, Diego; Murthy, Mathur R. N.

    2014-01-01

    For more than 30 years X-ray crystallography has been by far the most powerful approach for determining the structures of viruses and viral proteins at atomic resolution. The information provided by these structures, which covers many important aspects of the viral life cycle such as cell-receptor recognition, viral entry, nucleic acid transfer and genome replication, has extensively enriched our vision of the virus world. Many of the structures available correspond to potential targets for antiviral drugs against important human pathogens. This article provides an overview of the current knowledge of different structural aspects of the above-mentioned processes. PMID:25485129

  1. Cytokine determinants of viral tropism

    Microsoft Academic Search

    Mohamed R. Mohamed; Masmudur M. Rahman; Eric Bartee; Grant McFadden

    2009-01-01

    The specificity of a given virus for a cell type, tissue or species — collectively known as viral tropism — is an important factor in determining the outcome of viral infection in any particular host. Owing to the increased prevalence of zoonotic infections and the threat of emerging and re-emerging pathogens, gaining a better understanding of the factors that determine

  2. Bovine viral diarrhea viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infections with bovine viral diarrhea viruses (BVDV) result in significant economic losses for beef and dairy producers worldwide. BVDV is actually an umbrella term for two species of viruses, BVDV1 and BVDV2, within the Pestivirus genus of the Flavivirus family. While denoted as a bovine pathogen...

  3. ATRAZINE INCREASES RANAVIRUS SUSCEPTIBILITY IN THE TIGER SALAMANDER, AMBYSTOMA TIGRINUM

    Microsoft Academic Search

    Diane Denise Forson; Andrew Storfer

    2006-01-01

    Pathogenic diseases and environmental contaminants are two of the leading hypotheses for global amphibian declines, yet few studies have examined the influence of contaminants on disease susceptibility. In this study, we examined effects of ecologically relevant doses of atrazine (0, 1.6, 16, and 160 lg\\/L), sodium nitrate (0, 6.8, 68 mg\\/L), and their interactions on susceptibility of four laboratory-bred tiger

  4. Thymic pathogenicity of an HIV-1 envelope is associated with increased CXCR4 binding efficiency and V5-gp41-dependent activity, but not V1/V2-associated CD4 binding efficiency and viral entry

    SciTech Connect

    Meissner, Eric G. [Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599 (United States); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599 (United States); Coffield, Vernon M. [Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599 (United States); Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599 (United States); Su Lishan [Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599 (United States) and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599 (United States)]. E-mail: lsu@med.unc.edu

    2005-06-05

    We previously described a thymus-tropic HIV-1 envelope (R3A Env) from a rapid progressor obtained at the time of transmission. An HIV-1 molecular recombinant with the R3A Env supported extensive replication and pathogenesis in the thymus and did not require Nef. Another Env from the same patient did not display the same thymus-tropic pathogenesis (R3B Env). Here, we show that relative to R3B Env, R3A Env enhances viral entry of T cells, increases fusion-induced cytopathicity, and shows elevated binding efficiency for both CD4 and CXCR4, but not CCR5, in vitro. We created chimeric envelopes to determine the region(s) responsible for each in vitro phenotype and for thymic pathogenesis. Surprisingly, while V1/V2 contributed to enhanced viral entry, CD4 binding efficiency, and cytopathicity in vitro, it made no contribution to thymic pathogenesis. Rather, CXCR4 binding efficiency and V5-gp41-associated activity appear to independently contribute to thymic pathogenesis of the R3A Env. These data highlight the contribution of unique HIV pathogenic factors in the thymic microenvironment and suggest that novel mechanisms may be involved in Env pathogenic activity in vivo.

  5. Susceptibility of Xenopus laevis tadpoles to infection by the ranavirus Frog-Virus 3 correlates with a reduced and delayed innate immune response in comparison with adult frogs

    PubMed Central

    De Jesús Andino, Francisco; Chen, Guangchun; Li, Zhenghui; Grayfer, Leon; Robert, Jacques

    2012-01-01

    Xenopus laevis adults mount effective immune responses to ranavirus Frog Virus 3 (FV3) infections and clear the pathogen within 2–3 weeks. In contrast, most tadpoles cannot clear FV3 and succumb to infections within a month. While larval susceptibility has been attributed to ineffective adaptive immunity, the contribution of innate immune components has not been addressed. Accordingly, we performed a comprehensive gene expression analysis on FV3-infected tadpoles and adults. In comparison to adults, leukocytes and tissues of infected tadpoles exhibited modest (10–100 time lower than adult) and delayed (3 day later than adult) increase in expression of inflammation-associated (TNF-?, IL-1? and IFN-?) and antiviral (Mx1) genes. In contrast, these genes were readily and robustly upregulated in tadpoles upon bacterial stimulation. Furthermore, greater proportions of larval than adult PLs were infected by FV3. Our study suggests that tadpole susceptibility to FV3 infection is partially due to poor virus-elicited innate immune responses. PMID:22819836

  6. DEMONSTRATION OF H5N1 HIGHLY PATHOGENIC AVIAN INFLUENZA VIRAL ANTIGEN IN FORMALIN-FIXED AVIAN TISSUE SPECIMENS BY AN AVIDIN-BIOTIN IMMUNOHISTOCHEMISTRY PROCEDURE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The avidin-biotin immunohistochemistry (IHC) procedure has been used successfully to identify a variety of bacterial, viral and cellular antigens in formalin-fixed tissues. The procedure is rapid, reproducible, and specific making it an extremely useful method for screening diagnostic specimens. T...

  7. Viral Phylodynamics

    PubMed Central

    Volz, Erik M.; Koelle, Katia; Bedford, Trevor

    2013-01-01

    Viral phylodynamics is defined as the study of how epidemiological, immunological, and evolutionary processes act and potentially interact to shape viral phylogenies. Since the coining of the term in 2004, research on viral phylodynamics has focused on transmission dynamics in an effort to shed light on how these dynamics impact viral genetic variation. Transmission dynamics can be considered at the level of cells within an infected host, individual hosts within a population, or entire populations of hosts. Many viruses, especially RNA viruses, rapidly accumulate genetic variation because of short generation times and high mutation rates. Patterns of viral genetic variation are therefore heavily influenced by how quickly transmission occurs and by which entities transmit to one another. Patterns of viral genetic variation will also be affected by selection acting on viral phenotypes. Although viruses can differ with respect to many phenotypes, phylodynamic studies have to date tended to focus on a limited number of viral phenotypes. These include virulence phenotypes, phenotypes associated with viral transmissibility, cell or tissue tropism phenotypes, and antigenic phenotypes that can facilitate escape from host immunity. Due to the impact that transmission dynamics and selection can have on viral genetic variation, viral phylogenies can therefore be used to investigate important epidemiological, immunological, and evolutionary processes, such as epidemic spread [2], spatio-temporal dynamics including metapopulation dynamics [3], zoonotic transmission, tissue tropism [4], and antigenic drift [5]. The quantitative investigation of these processes through the consideration of viral phylogenies is the central aim of viral phylodynamics. PMID:23555203

  8. Study of the kinetics of antibodies titres against viral pathogens and detection of rotavirus and parainfluenza 3 infections in captive crias of guanacos (Lama guanicoe).

    PubMed

    Marcoppido, G; Olivera, V; Bok, K; Parreño, V

    2011-02-01

    A longitudinal study was conducted to investigate the presence of antibodies (Ab) to Rotavirus (RV), Parainfluenza-3 virus (PI-3), Bovine Herpesvirus-1 (BoHV-1), Bovine Viral Diarrhoea virus (BVDV-1) and Bluetongue virus (BTV) in eleven guanaco's crias (chulengos) relocated from Rio Negro to Buenos Aires Province (Argentina) and reared in captivity for a year in an experimental field. Serum samples were collected periodically to detect the evidence of viral infections. Faecal samples were collected to investigate RV shedding. We detected the evidence of Ab to RV from the beginning of the experience, suggesting the presence of maternal Ab against the virus. RV infection was detected in seven of the eleven chulengos, by seroconversion (4), virus shedding in stools (1) or both (2). In all cases, the RV strain was typed as [P1]G8, the same G/P type combination detected in captive chulengos with acute diarrhoea sampled in Rio Negro, in 2001. In contrast, we could not detect antibodies against PI-3, BoHV-1, BVDV or BT in any of initial samples. No Abs against BoHV-1, BVDV or BTV were detected in the chulengos throughout the study. However, all the chulengos became asymptomatically seropositive to PI-3 by the 7 month after arrival. This study suggest that wild-born guanacos raised in captivity can be relatively susceptible to common livestock viral infections, such as RV and PI-3, which are easily spread among chulengos. PMID:21062425

  9. Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines for Shigella, Salmonella, enterotoxigenic E. coli (ETEC) enterohemorragic E. coli (EHEC) and Campylobacter jejuni.

    PubMed

    O'Ryan, Miguel; Vidal, Roberto; Del Canto, Felipe; Carlos Salazar, Juan; Montero, David

    2015-03-01

    In Part II we discuss the following bacterial pathogens: Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic) and Campylobacter jejuni. In contrast to the enteric viruses and Vibrio cholerae discussed in Part I of this series, for the bacterial pathogens described here there is only one licensed vaccine, developed primarily for Vibrio cholerae and which provides moderate protection against enterotoxigenic E. coli (ETEC) (Dukoral®), as well as a few additional candidates in advanced stages of development for ETEC and one candidate for Shigella spp. Numerous vaccine candidates in earlier stages of development are discussed. PMID:25715096

  10. Ecological Database of the World's Insect Pathogens

    NSDL National Science Digital Library

    0000-00-00

    A search enabled relational database focusing on pathogens of insects including non-viral, viral, and nematodes, for purposes of insect control. This page does not include information about Bacillus thuringiensis (Bt). (shows 2002 as last update)

  11. A SEROLOGIC ASSESSMENT OF EXPOSURE TO VIRAL PATHOGENS AND LEPTOSPIRA IN AN URBAN RACCOON (PROCYON LOTOR) POPULATION INHABITING A LARGE ZOOLOGICAL PARK

    Microsoft Academic Search

    Randall E. Junge; Karen Bauman; Melanie King; Matthew E. Gompper

    2007-01-01

    In urban environments, raccoons (Procyon lotor) may act as reservoirs for an array of pathogenic organ- isms, presenting spillover risks for human, domestic animal, and captive (zoo) animal populations. Over 5 yr, 159 raccoons from a high-density raccoon population in St. Louis, Missouri (USA), were surveyed for exposure to canine distemper virus (CDV), canine adenovirus 1 (CAV-1); feline parvovirus (FPV;

  12. Detection of Viral Pathogens by Reverse Transcriptase PCR and of Microbial Indicators by Standard Methods in the Canals of the Florida Keys

    Microsoft Academic Search

    DALE W. GRIFFIN; CHARLES J. GIBSON; ERIN K. LIPP; KELLEY RILEY; JOHN H. PAUL; JOAN B. ROSE

    1999-01-01

    In order to assess the microbial water quality in canal waters throughout the Florida Keys, a survey was conducted to determine the concentration of microbial fecal indicators and the presence of human pathogenic microorganisms. A total of 19 sites, including 17 canal sites and 2 nearshore water sites, were assayed for total coliforms, fecal coliforms, Escherichia coli, Clostridium perfringens, enterococci,

  13. Characterisation of acute respiratory infections at a United Kingdom paediatric teaching hospital: observational study assessing the impact of influenza A (2009 pdmH1N1) on predominant viral pathogens

    PubMed Central

    2014-01-01

    Background According to the World Health Organisation, influenza A (2009 pdmH1N1) has moved into the post-pandemic phase, but there were still high numbers of infections occurring in the United Kingdom in 2010-11. It is therefore important to examine the burden of acute respiratory infections at a large children’s hospital to determine pathogen prevalence, occurrence of co-infection, prevalence of co-morbidities and diagnostic yield of sampling methods. Methods This was a retrospective study of respiratory virus aetiology in acute admissions to a paediatric teaching hospital in the North West of England between 1st April 2010 and 31st March 2011. Respiratory samples were analysed either with a rapid RSV test if the patient had symptoms suggestive of bronchiolitis, followed by multiplex PCR testing for ten respiratory viruses, or with multiplex PCR testing alone if the patient had suspected other ARI. Patient demographics and data regarding severity of illness, presence of co-morbidities and respiratory virus sampling method were retrieved from case notes. Results 645 patients were admitted during the study period. 82/645 (12.7%) patients were positive for 2009 pdmH1N1, of whom 24 (29.2%) required PICU admission, with 7.3% mortality rate. Viral co-infection occurred in 48/645 (7.4%) patients and was not associated with more severe disease. Co-morbidities were present more frequently in older children, but there was no significant difference in prevalence of co-morbidity between 2009 pdmH1N1 patients and those with other ARI. NPA samples had the highest diagnostic yield with 192/210 (91.4%) samples yielding an organism. Conclusions Influenza A (2009 pdmH1N1) is an ongoing cause of occasionally severe disease affecting both healthy children and those with co-morbidities. Surveillance of viral pathogens provides valuable information on patterns of disease. PMID:24948099

  14. Ecology of Waterborne Pathogens Instructor

    E-print Network

    Ma, Lena

    Ecology of Waterborne Pathogens Instructor: Max Teplitski, Associate Professor Phone: 273 Prerequisites: MCB3020 (Basic Biology of Microorganisms), or MCB3023 or MCB4203 (Bacterial and Viral Pathogens and methodologies for identifying and characterizing pathogens and their behaviors outside of their human hosts

  15. Comparative genomic analyses of frog virus 3, type species of the genus Ranavirus (family Iridoviridae).

    PubMed

    Tan, Wendy G H; Barkman, Todd J; Gregory Chinchar, V; Essani, Karim

    2004-05-20

    Frog virus 3 (FV3) is the type species member of the genus Ranavirus (family Iridoviridae). To better understand the molecular mechanisms involved in the replication of FV3, including transcription of its highly methylated DNA genome, we have determined the complete nucleotide sequence of the FV3 genome. The FV3 genome is 105903 bp long excluding the terminal redundancy. The G + C content of FV3 genome is 55% and it encodes 98 nonoverlapping potential open reading frames (ORFs) containing 50-1293 amino acids. Eighty-four ORFs have significant homology to known proteins of other iridoviruses, whereas twelve of these unique FV3 proteins do not share homology to any known protein. A microsatellite containing a stretch of 34 tandemly repeated CA dinucleotide in a noncoding region was detected. To date, no such sequence has been reported in any animal virus. PMID:15165820

  16. Molecular testing for viral and bacterial enteric pathogens: gold standard for viruses, but don't let culture go just yet?

    PubMed

    Bloomfield, Maxim G; Balm, Michelle N D; Blackmore, Timothy K

    2015-04-01

    Contemporary diagnostic microbiology is increasingly adopting molecular methods as front line tests for a variety of samples. This trend holds true for detection of enteric pathogens (EP), where nucleic acid amplification tests (NAAT) for viruses are well established as the gold standard, and an increasing number of commercial multi-target assays are now available for bacteria and parasites. NAAT have significant sensitivity and turnaround time advantages over traditional methods, potentially returning same-day results. Multiplex panels offer an attractive 'one-stop shop' that may provide workflow and cost advantages to laboratories processing large sample volumes. However, there are a number of issues which need consideration. Reflex culture is required for antibiotic susceptibility testing and strain typing when needed for food safety and other epidemiological investigations. Surveillance systems will need to allow for differences in disease incidence due to the enhanced sensitivity of NAAT. Laboratories should be mindful of local epidemiology when selecting which pathogens to include in multiplex panels, and be thoughtful regarding which pathogens will not be detected. Multiplex panels may not be appropriate in certain situations, such as hospital-onset diarrhoea, where Clostridium difficile testing might be all that is required, and laboratories may wish to retain the flexibility to run single tests in such situations. The clinical impact of rapid results is also likely to be relatively minor, as infective diarrhoea is a self-limiting illness in the majority of cases. Laboratories will require strategies to assist users in the interpretation of the results produced by NAAT, particularly where pathogens are detected at low levels with uncertain clinical significance. These caveats aside, faecal NAAT are increasingly being used and introduce a new era of diagnosis of gastrointestinal infection. PMID:25719855

  17. Uncoupling of the dynamics of host-pathogen interaction uncovers new mechanisms of viral interferon antagonism at the single-cell level.

    PubMed

    Rand, Ulfert; Hillebrand, Upneet; Sievers, Stephanie; Willenberg, Steffi; Köster, Mario; Hauser, Hansjörg; Wirth, Dagmar

    2014-07-01

    Antiviral defence in mammals is mediated through type-I interferons (IFNs). Viruses antagonise this process through expression of IFN antagonist proteins (IAPs). Understanding and modelling of viral escape mechanisms and the dynamics of IAP action has the potential to facilitate the development of specific and safe drugs. Here, we describe the dynamics of interference by selected viral IAPs, NS1 from Influenza A virus and NS3/4A from Hepatitis C virus. We used Tet-inducible IAP gene expression to uncouple this process from virus-driven dynamics. Stochastic activation of the IFN-? gene required the use of single-cell live imaging to define the efficacy of the inhibitors during the virus-induced signalling processes. We found significant correlation between the onset of IAP expression and halted IFN-? expression in cells where IFN-? induction had already occurred. These data indicate that IAPs not only prevent antiviral signalling prior to IFN-? induction, but can also stop the antiviral response even after it has been activated. We found reduced NF-?B activation to be the underlying mechanism by which activated IFN expression can be blocked. This work demonstrates a new mechanism by which viruses can antagonise the IFN response. PMID:24895433

  18. Uncoupling of the dynamics of host–pathogen interaction uncovers new mechanisms of viral interferon antagonism at the single-cell level

    PubMed Central

    Rand, Ulfert; Hillebrand, Upneet; Sievers, Stephanie; Willenberg, Steffi; Köster, Mario; Hauser, Hansjörg; Wirth, Dagmar

    2014-01-01

    Antiviral defence in mammals is mediated through type-I interferons (IFNs). Viruses antagonise this process through expression of IFN antagonist proteins (IAPs). Understanding and modelling of viral escape mechanisms and the dynamics of IAP action has the potential to facilitate the development of specific and safe drugs. Here, we describe the dynamics of interference by selected viral IAPs, NS1 from Influenza A virus and NS3/4A from Hepatitis C virus. We used Tet-inducible IAP gene expression to uncouple this process from virus-driven dynamics. Stochastic activation of the IFN-? gene required the use of single-cell live imaging to define the efficacy of the inhibitors during the virus-induced signalling processes. We found significant correlation between the onset of IAP expression and halted IFN-? expression in cells where IFN-? induction had already occurred. These data indicate that IAPs not only prevent antiviral signalling prior to IFN-? induction, but can also stop the antiviral response even after it has been activated. We found reduced NF-?B activation to be the underlying mechanism by which activated IFN expression can be blocked. This work demonstrates a new mechanism by which viruses can antagonise the IFN response. PMID:24895433

  19. A serologic assessment of exposure to viral pathogens and Leptospira in an urban raccoon (Procyon lotor) population inhabiting a large zoological park.

    PubMed

    Junge, Randall E; Bauman, Karen; King, Melanie; Gompper, Matthew E

    2007-03-01

    In urban environments, raccoons (Procyon lotor) may act as reservoirs for an array of pathogenic organisms, presenting spillover risks for human, domestic animal, and captive (zoo) animal populations. Over 5 yr, 159 raccoons from a high-density raccoon population in St. Louis, Missouri (USA), were surveyed for exposure to canine distemper virus (CDV), canine adenovirus 1 (CAV-1); feline parvovirus (FPV; =feline panleukopenia), and several serovars of Leptospira interrogans. Exposure to each of the viruses and two Leptospira serovars (grippotyphosa and icterohemorrhagiae) was detected (prevalence of CDV = 54.1%; FPV = 49.7%; CAV-1 = 6.9%; L. interrogans icterohemorrhagiae = 8.9%; L. interrogans grippotyphosa = 6.3%). Eighty percent of raccoons showed evidence of exposure to at least one of the five primary pathogens, and 39% were positive for multiple species. Among the viruses, there was a significant co-occurrence of CDV and CAV-1. Longitudinal data on a subset of animals revealed that among individuals who were diagnosed as seropositive on first capture, 33-100% became seronegative for the pathogen of interest when reexamined at a later date. Thus, free-ranging urban raccoons have been exposed to multiple infectious agents, some of which may pose risks to humans and to nonvaccinated domestic and captive animal populations. PMID:17469271

  20. Cytokine determinants of viral tropism

    PubMed Central

    McFadden, Grant; Mohamed, Mohamed R.; Rahman, Masmudur M.; Bartee, Eric

    2015-01-01

    The specificity of a given virus for a ceil type, tissue or species — collectively known as viral tropism — is an important factor in determining the outcome of viral infection in any particular host. Owing to the increased prevalence of zoonotic infections and the threat of emerging and re-emerging pathogens, gaining a better understanding of the factors that determine viral tropism has become particularly important. In this Review, we summarize our current understanding of the central role of antiviral and pro-inflammatory cytokines, particularly the interferons and tumour necrosis factor, in dictating viral tropism and how these cytokine pathways can be exploited therapeutically for cancer treatment and to better counter future threats from emerging zoonotic pathogens. PMID:19696766

  1. A Novel Cytotoxic Sequence Contributes to Influenza A Viral Protein PB1-F2 Pathogenicity and Predisposition to Secondary Bacterial Infection

    PubMed Central

    Samarasinghe, Amali; Vogel, Peter; Green, Amanda M.; Weinlich, Ricardo; McCullers, Jonathan A.

    2014-01-01

    Enhancement of cell death is a distinguishing feature of H1N1 influenza virus A/Puerto Rico/8/34 protein PB1-F2. Comparing the sequences (amino acids [aa] 61 to 87 using PB1-F2 amino acid numbering) of the PB1-F2-derived C-terminal peptides from influenza A viruses inducing high or low levels of cell death, we identified a unique I68, L69, and V70 motif in A/Puerto Rico/8/34 PB1-F2 responsible for promotion of the peptide's cytotoxicity and permeabilization of the mitochondrial membrane. When administered to mice, a 27-mer PB1-F2-derived C-terminal peptide with this amino acid motif caused significantly greater weight loss and pulmonary inflammation than the peptide without it (due to I68T, L69Q, and V70G mutations). Similar to the wild-type peptide, A/Puerto Rico/8/34 elicited significantly higher levels of macrophages, neutrophils, and cytokines in the bronchoalveolar lavage fluid of mice than its mutant counterpart 7 days after infection. Additionally, infection of mice with A/Puerto Rico/8/34 significantly enhanced the levels of morphologically transformed epithelial and immune mononuclear cells recruited in the airways compared with the mutant virus. In the mouse bacterial superinfection model, both peptide and virus with the I68, L69, and V70 sequence accelerated development of pneumococcal pneumonia, as reflected by increased levels of viral and bacterial lung titers and by greater mortality. Here we provide evidence suggesting that the newly identified cytotoxic sequence I68, L69, and V70 of A/Puerto Rico/8/34 PB1-F2 contributes to the pathogenesis of both primary viral and secondary bacterial infections. PMID:24173220

  2. Viral and cellular microRNAs as determinants of viral pathogenesis and immunity

    PubMed Central

    Gottwein, Eva; Cullen, Bryan R.

    2011-01-01

    Summary MicroRNAs have recently emerged as key post-transcriptional regulators of gene expression in multicellular eukaryotes. It is increasingly clear that microRNAs of both viral and cellular origin can positively or negatively influence viral replication. Viral microRNAs can directly alter host physiology, including components of the immune system, and host microRNAs can directly alter the virus life cycle. Here, we discuss what is known about how viral and cellular microRNAs influence viral replication and pathogenic potential through their regulation of viral mRNAs or by reshaping cellular gene expression. PMID:18541214

  3. Semen-Derived Enhancer of Viral Infection (SEVI) Binds Bacteria, Enhances Bacterial Phagocytosis by Macrophages, and Can Protect against Vaginal Infection by a Sexually Transmitted Bacterial Pathogen

    PubMed Central

    Easterhoff, David; Ontiveros, Fernando; Brooks, Lauren R.; Kim, Yoel; Ross, Brittany; Silva, Jharon N.; Olsen, Joanna S.; Feng, Changyong; Hardy, Dwight J.; Dunman, Paul M.

    2013-01-01

    The semen-derived enhancer of viral infection (SEVI) is a positively charged amyloid fibril that is derived from a self-assembling proteolytic cleavage fragment of prostatic acid phosphatase (PAP248-286). SEVI efficiently facilitates HIV-1 infection in vitro, but its normal physiologic function remains unknown. In light of the fact that other amyloidogenic peptides have been shown to possess direct antibacterial activity, we investigated whether SEVI could inhibit bacterial growth. Neither SEVI fibrils nor the unassembled PAP248-286 peptide had significant direct antibacterial activity in vitro. However, SEVI fibrils bound to both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli and Neisseria gonorrhoeae) bacteria, in a charge-dependent fashion. Furthermore, SEVI fibrils but not the monomeric PAP248-286 peptide promoted bacterial aggregation and enhanced the phagocytosis of bacteria by primary human macrophages. SEVI also enhanced binding of bacteria to macrophages and the subsequent release of bacterially induced proinflammatory cytokines (tumor necrosis factor alpha [TNF-?], interleukin-6 [IL-6], and IL-1?). Finally, SEVI fibrils inhibited murine vaginal colonization with Neisseria gonorrhoeae. These findings demonstrate that SEVI has indirect antimicrobial activity and that this activity is dependent on both the cationic charge and the fibrillar nature of SEVI. PMID:23507280

  4. The Ac124 protein is not essential for the propagation of Autographa californica multiple nucleopolyhedrovirus, but it is a viral pathogenicity factor.

    PubMed

    Liang, Changyong; Lan, Dandan; Zhao, Shuling; Liu, Lulu; Xue, Yanan; Zhang, Yongli; Wang, Yun; Chen, Xinwen

    2015-01-01

    orf124 (ac124) of AcMNPV is one of the highly conserved unique genes in group I lepidopteran nucleopolyhedroviruses. So far, its function remains unknown. In this study, infection with a virus expressing an ac124-gfp fusion showed that Ac124 localized to the cytoplasm throughout the infection. In addition, an ac124 knockout virus was generated to determine the role of ac124 in the baculovirus life cycle. Our results showed that an ac124 knockout AcMNPV could produce infectious budded viruses (BVs) and occlusion bodies (OBs) like those produced by the wild virus and ac124 repair virus. These three viruses had similar growth kinetics during the infection phase. There was no significant difference in nucleocapsids, occlusion-derived viruses and OBs visualized by electron microscopy. The ac124 deletion mutant did not reduce AcMNPV infectivity for S. exigua in an LD50 bioassay. However, it took 20 h longer for the ac124 deletion mutant to kill S. exigua than wild-type virus in the LT50 bioassay. Altogether, these results demonstrate that ac124 is not required for viral replication, but it accelerates the killing of infected larvae. PMID:25380680

  5. Molecular biology of bovine viral diarrhea virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea viruses (BVDV) are arguably the most important viral pathogen of ruminants worldwide and can cause severe economic loss. Clinical symptoms of the disease caused by BVDV range from subclinical to severe acute hemorrhagic syndrome, with the severity of disease being strain depend...

  6. The impact of viral tropism and housing conditions on the transmission of three H5/H7 low pathogenic avian influenza viruses in chickens.

    PubMed

    Claes, G; Welby, S; Van Den Berg, T; Van Der Stede, Y; Dewulf, J; Lambrecht, B; Marché, S

    2013-11-01

    In this study, shedding and transmission of three H5/H7 low pathogenic avian influenza viruses (LPAIVs) in poultry was characterized and the impact of floor system on transmission was assessed. Transmission experiments were simultaneously conducted with two groups of animals housed on either a grid or a floor covered with litter. Transmission was observed for H5N2 A/Ch/Belgium/150VB/99 LPAIV. This virus was shed almost exclusively via the oropharynx and no impact of floor system was seen. Transmission was also seen for H7N1 A/Ch/Italy/1067/v99 LPAIV, which was shed via both the oropharynx and cloaca. A slight increase in transmission was seen for animals housed on litter. H5N3 A/Anas Platyrhynchos/Belgium/09-884/2008 LPAIV did not spread to susceptible animals, regardless of the floor system. This study shows that environmental factors such as floor systems used in poultry barns may act upon the transmission of LPAIVs. However, the level of influence depends on the virus under consideration and, more specifically, its principal replication sites. PMID:23398968

  7. Molecular basis of viral and microbial pathogenesis

    SciTech Connect

    Rott, R.; Goebel, W.

    1988-01-01

    The contents of this book are: Correlation Between Viroid Structure and Pathogenicty; Antigenicity of the Influenza Haemagglutinia Membrane Glycoprotein; Viral Glycoproteins as Determinants of Pathogenicity; Virus Genes Involved in Host Range and Pathogenicity; Molecular Heterogenetiy of Pathogenic Herpus Viruses; Recombination of Foreign (Viral) DNA with Host Genome: Studies in Vivo and in a Cell-Free system; Disorders of Cellular Neuro-Functions by Persistent Viral Infection; Pathogenic Aspects of Measles Virus-Persistent Infections in Man; Analysis of the Dual Lineage Specificity of E26 Avian Leukemia Virus; Mx Gene Control of Influenza Virus Susceptibility; Shiga and Shika-Like Toxins: A Family of Related Cytokinons; and Molecular Mechanisms of Pathogenicity in Shigella Flexneri.

  8. Viral Infections

    MedlinePLUS

    ... much smaller than bacteria. Viruses cause familiar infectious diseases such as the common cold, flu and warts. ... can help prevent you from getting many viral diseases. NIH: National Institute of Allergy and Infectious Diseases

  9. Viral pneumonia

    MedlinePLUS

    More serious infections can result in respiratory failure, liver failure, and heart failure. Sometimes, bacterial infections occur during or just after viral pneumonia, which may lead to more serious forms ...

  10. Viral Gastroenteritis

    MedlinePLUS

    ... and hospitalization. Untreated severe dehydration can cause serious health problems such as organ damage, shock, or coma—a sleeplike state in which a person is not conscious. [ Top ] What causes viral gastroenteritis? Four types of ...

  11. Viral Meningitis

    MedlinePLUS

    ... Non-infectious Meningitis Resources for Healthcare Professionals Related Links Vaccine Schedules Preteen & Teen Vaccines Meningococcal Disease Viral ... lymphocytic choriomeningitis virus . Â Top of Page Related Links Mumps MMR Vaccine Chickenpox Chickenpox Vaccine Enteroviruses Arboviruses ...

  12. Present and future projections of habitat suitability of the Asian tiger mosquito, a vector of viral pathogens, from global climate simulation

    PubMed Central

    Proestos, Y.; Christophides, G. K.; Ergüler, K.; Tanarhte, M.; Waldock, J.; Lelieveld, J.

    2015-01-01

    Climate change can influence the transmission of vector-borne diseases (VBDs) through altering the habitat suitability of insect vectors. Here we present global climate model simulations and evaluate the associated uncertainties in view of the main meteorological factors that may affect the distribution of the Asian tiger mosquito (Aedes albopictus), which can transmit pathogens that cause chikungunya, dengue fever, yellow fever and various encephalitides. Using a general circulation model at 50 km horizontal resolution to simulate mosquito survival variables including temperature, precipitation and relative humidity, we present both global and regional projections of the habitat suitability up to the middle of the twenty-first century. The model resolution of 50 km allows evaluation against previous projections for Europe and provides a basis for comparative analyses with other regions. Model uncertainties and performance are addressed in light of the recent CMIP5 ensemble climate model simulations for the RCP8.5 concentration pathway and using meteorological re-analysis data (ERA-Interim/ECMWF) for the recent past. Uncertainty ranges associated with the thresholds of meteorological variables that may affect the distribution of Ae. albopictus are diagnosed using fuzzy-logic methodology, notably to assess the influence of selected meteorological criteria and combinations of criteria that influence mosquito habitat suitability. From the climate projections for 2050, and adopting a habitat suitability index larger than 70%, we estimate that approximately 2.4 billion individuals in a land area of nearly 20 million km2 will potentially be exposed to Ae. albopictus. The synthesis of fuzzy-logic based on mosquito biology and climate change analysis provides new insights into the regional and global spreading of VBDs to support disease control and policy making. PMID:25688015

  13. Present and future projections of habitat suitability of the Asian tiger mosquito, a vector of viral pathogens, from global climate simulation.

    PubMed

    Proestos, Y; Christophides, G K; Ergüler, K; Tanarhte, M; Waldock, J; Lelieveld, J

    2015-04-01

    Climate change can influence the transmission of vector-borne diseases (VBDs) through altering the habitat suitability of insect vectors. Here we present global climate model simulations and evaluate the associated uncertainties in view of the main meteorological factors that may affect the distribution of the Asian tiger mosquito (Aedes albopictus), which can transmit pathogens that cause chikungunya, dengue fever, yellow fever and various encephalitides. Using a general circulation model at 50 km horizontal resolution to simulate mosquito survival variables including temperature, precipitation and relative humidity, we present both global and regional projections of the habitat suitability up to the middle of the twenty-first century. The model resolution of 50 km allows evaluation against previous projections for Europe and provides a basis for comparative analyses with other regions. Model uncertainties and performance are addressed in light of the recent CMIP5 ensemble climate model simulations for the RCP8.5 concentration pathway and using meteorological re-analysis data (ERA-Interim/ECMWF) for the recent past. Uncertainty ranges associated with the thresholds of meteorological variables that may affect the distribution of Ae. albopictus are diagnosed using fuzzy-logic methodology, notably to assess the influence of selected meteorological criteria and combinations of criteria that influence mosquito habitat suitability. From the climate projections for 2050, and adopting a habitat suitability index larger than 70%, we estimate that approximately 2.4 billion individuals in a land area of nearly 20 million km(2) will potentially be exposed to Ae. albopictus. The synthesis of fuzzy-logic based on mosquito biology and climate change analysis provides new insights into the regional and global spreading of VBDs to support disease control and policy making. PMID:25688015

  14. Viral-Associated Trichodysplasia

    PubMed Central

    Wanat, Karolyn A.; Holler, Phillip D.; Dentchev, Tzvete; Simbiri, Kenneth; Robertson, Erle; Seykora, John T.; Rosenbach, Misha

    2012-01-01

    Background Viral-associated trichodysplasia of immunosuppression is a rare cutaneous eruption that is characterized by follicularly based shiny papules and alopecia with characteristic histopathologic findings of abnormally anagen follicules with excessive inner root sheath differentiation. Prior reports have described the histopathologic characteristics on vertical sections; however, to our knowledge, immunohistochemical analysis of polyomavirus proteins has not been previously performed. Observations We discuss the thorough diagnostic evaluation and therapy of an unusual case of viral-associated trichodysplasia due to a newly described human polyomavirus that occurred in a patient with post-treatment chronic lymphocytic leukemia and an abnormal white blood cell count. Unique to our study is the immunohistochemical staining for the polyomavirus middle T antigen, which demonstrated positive staining of cellular inclusions within keratinocytes that compose the inner root sheath. Further evaluation with scanning electron microscopy and polymerase chain reaction analysis of viral DNA confirmed the presence of the virus. Treatment with topical cidofovir resulted in dramatic clinical improvement and hair regrowth. Conclusions Several tools, including immunohistochemical staining for the polyomavirus middle T antigen, can be used to identify the pathogenic virus associated with viral-associated trichodysplasia. This case highlights the utility of multiple diagnostic modalities and a robust response to a topical therapeutic agent, cidofovir. PMID:22351821

  15. Aetiology of viral central nervous system infection, a Malaysian study

    Microsoft Academic Search

    Yean Kong Yong; Heng Thay Chong; Kum Thong Wong; Chong Tin Tan; Shamala Devi

    Over 100 viruses are known to cause acute viral encephalitis in human. In order to diagnose a viral central nervous system infection, various laboratory diagnosis methods have been used. In this study, we examined 220 cerebrospinal fluid samples that were received at the Diagnostic Virology Laboratory of University Malaya Medical Centre between year 2004 to 2006, by viral isolation, pathogen

  16. Synthesis of minus-strand copies of a viral transgene during viral infections of transgenic plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants can be genetically engineered to express viral sequences, often resulting in resistance to the virus from which the sequence was derived. The generally accepted mechanism for this pathogen induced resistance is gene silencing. Previous work has demonstrated that viral transgenes can be incorp...

  17. Development of an EvaGreen-based multiplex real-time PCR assay with melting curve analysis for simultaneous detection and differentiation of six viral pathogens of porcine reproductive and respiratory disorder.

    PubMed

    Rao, Pinbin; Wu, Haigang; Jiang, Yonghou; Opriessnig, Tanja; Zheng, Xiaowen; Mo, Yecheng; Yang, Zongqi

    2014-11-01

    Concurrent infection of pigs with two or more pathogens is common in pigs under intensive rearing conditions. Porcine circovirus type 2 (PCV2), porcine parvovirus (PPV), porcine reproductive and respiratory syndrome virus (PRRSV), classical swine fever virus (CSFV), Japanese encephalitis virus (JEV) and pseudorabies virus (PRV) are all associated with reproductive or respiratory disorders or both and can cause significant economic losses in pig production worldwide. An EvaGreen-based multiplex real-time PCR (EG-mPCR) with melting curve analysis was developed in this study for simultaneous detection and differentiation of these six viruses in pigs. This method is able to detect and distinguish PCV2, PPV, PRRSV, CSFV, JEV and PRV with the limits of detection ranging from 100 to 500 copies/?L, high reproducibility, and intra-assay and inter-assay variation ranging from 0.11 to 3.20%. After validation, a total of 118 field samples were tested by the newly developed EG-mPCR. PCV2 was identified in 23%, PPV in 15%, PRRSV in 17% and PRV in 5% of the samples. Concurrent PCV2 and PRRSV infection was detected in 6.7%, PCV2 and PPV in 5% and PPV2 and PRRSV infection was detected in 5% of the cases. The agreement of the EG-mPCR and conventional PCR tests was 99.2%. This EG-mPCR will be a useful, rapid, reliable and cost-effective alternative for routine surveillance testing of viral infections in pigs. PMID:25102430

  18. Viral hepatocarcinogenesis

    PubMed Central

    Tsai, W-L; Chung, RT

    2011-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide. Despite recent advances in the diagnosis and treatment of HCC, its prognosis remains dismal. Infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are the major risk factors for HCC. Although both are hepatotropic viral infections, there are important differences between the oncogenic mechanisms of these two viruses. In addition to the oncogenic potential of its viral proteins, HBV, as a DNA virus, can integrate into host DNA and directly transform hepatocytes. In contrast, HCV, an RNA virus, is unable to integrate into the host genome, and viral protein expression has a more critical function in hepatocarcinogenesis. Both HBV and HCV proteins have been implicated in disrupting cellular signal transduction pathways that lead to unchecked cell growth. Most HCC develops in the cirrhotic liver, but the linkage between cirrhosis and HCC is likely multifactorial. In this review, we summarize current knowledge regarding the pathogenetic mechanisms of viral HCC. PMID:20228847

  19. Pathogen biology Meeting report

    E-print Network

    Gray, Matthew

    to ranaviruses as disease agents. This view changed by the late 1980s as a series of iridoviruses, later, Gainesville, FL, USA *Author for correspondence (dlesbarreres@laurentian.ca). Emerging infectious diseases Granoff while attempting to generate cell lines that would support growth of Lucke´ herpes- virus

  20. Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes

    Microsoft Academic Search

    Dan H. Barouch; Jennifer Kunstman; Marcelo J. Kuroda; Jörn E. Schmitz; Sampa Santra; Fred W. Peyerl; Georgia R. Krivulka; Kristin Beaudry; Michelle A. Lifton; Darci A. Gorgone; David C. Montefiori; Mark G. Lewis; Steven M. Wolinsky; Norman L. Letvin

    2002-01-01

    Potent virus-specific cytotoxic T lymphocyte (CTL) responses elicited by candidate AIDS vaccines have recently been shown to control viral replication and prevent clinical disease progression after pathogenic viral challenges in rhesus monkeys. Here we show that viral escape from CTL recognition can result in the eventual failure of this partial immune protection. Viral mutations that escape from CTL recognition have

  1. Human adenovirus: Viral pathogen with increasing importance

    PubMed Central

    2014-01-01

    The aim of this review is to describe the biology of human adenovirus (HAdV), the clinical and epidemiological characteristics of adenoviral epidemic keratoconjunctivitis and to present a practical update on its diagnosis, treatment, and prophylaxis. There are two well-defined adenoviral keratoconjunctivitis clinical syndromes: epidemic keratoconjunctivitis (EKC) and pharyngoconjunctival fever (PCF), which are caused by different HAdV serotypes. The exact incidence of adenoviral conjunctivitis is still poorly known. However, cases are more frequent during warmer months. The virus is endemic in the general population, and frequently causes severe disease in immunocompromised patients, especially the pediatric patients. Contagion is possible through direct contact or fomites, and the virus is extremely resistant to different physical and chemical agents. The clinical signs or symptoms of conjunctival infection are similar to any other conjunctivitis, with a higher incidence of pseudomembranes. In the cornea, adenoviral infection may lead to keratitis nummularis. Diagnosis is mainly clinical, but its etiology can be confirmed using cell cultures, antigen detection, polymerase chain reaction or immunochromatography. Multiple treatments have been tried for this disease, but none of them seem to be completely effective. Prevention is the most reliable and recommended strategy to control this contagious infection. PMID:24678403

  2. DEVELOPMENT OF HUMAN BIOMARKERS OF EXPOSURE TO WATERBORNE PATHOGENS

    EPA Science Inventory

    Contaminated drinking water is major source of waterborne diseases. EPA has published a drinking water contaminant candidate list (CCL) that contains a number of pathogens that potentially could be regulated in drinking water. Studies indicate that certain viral pathogens (adenov...

  3. Unexpected Rarity of the Pathogen Batrachochytrium dendrobatidis in Appalachian Plethodon Salamanders: 1957–2011

    PubMed Central

    Muletz, Carly; Caruso, Nicholas M.; Fleischer, Robert C.; McDiarmid, Roy W.; Lips, Karen R.

    2014-01-01

    Widespread population declines in terrestrial Plethodon salamanders occurred by the 1980s throughout the Appalachian Mountains, the center of global salamander diversity, with no evident recovery. We tested the hypothesis that the historic introduction and spread of the pathogenic fungus Batrachochytrium dendrobatidis (Bd) into the eastern US was followed by Plethodon population declines. We expected to detect elevated prevalence of Bd prior to population declines as observed for Central American plethodontids. We tested 1,498 Plethodon salamanders of 12 species (892 museum specimens, 606 wild individuals) for the presence of Bd, and tested 94 of those for Batrachochytrium salamandrivorans (Bs) and for ranavirus. Field samples were collected in 2011 from 48 field sites across a 767 km transect. Historic samples from museum specimens were collected at five sites with the greatest number and longest duration of collection (1957–987), four of which were sampled in the field in 2011. None of the museum specimens were positive for Bd, but four P. cinereus from field surveys were positive. The overall Bd prevalence from 1957–2011 for 12 Plethodon species sampled across a 757 km transect was 0.2% (95% CI 0.1–0.7%). All 94 samples were negative for Bs and ranavirus. We conclude that known amphibian pathogens are unlikely causes for declines in these Plethodon populations. Furthermore, these exceptionally low levels of Bd, in a region known to harbor Bd, may indicate that Plethodon specific traits limit Bd infection. PMID:25084159

  4. Cutaneous manifestations of viral hepatitis.

    PubMed

    Akhter, Ahmed; Said, Adnan

    2015-02-01

    There are several extrahepatic cutaneous manifestations associated with hepatitis B and hepatitis C virus infection. Serum sickness and polyarteritis nodosa are predominantly associated with hepatitis B infection, whereas mixed cryoglobulinemia associated vasculitis and porphyria cutanea tarda are more frequently seen in hepatitis C infection. The clinico-pathogenic associations of these skin conditions are not completely defined but appear to involve activation of the host immune system including the complement system. Management of the aforementioned cutaneous manifestations of viral hepatitis is often similar to that done in cases without viral hepatitis, with control of immune activation being a key strategy. In cases associated with hepatitis B and C, control of viral replication with specific antiviral therapy is also important and associated with improvement in most of the associated clinical manifestations. PMID:25809574

  5. Viral epigenetics.

    PubMed

    Milavetz, Barry I; Balakrishnan, Lata

    2015-01-01

    DNA tumor viruses including members of the polyomavirus, adenovirus, papillomavirus, and herpes virus families are presently the subject of intense interest with respect to the role that epigenetics plays in control of the virus life cycle and the transformation of a normal cell to a cancer cell. To date, these studies have primarily focused on the role of histone modification, nucleosome location, and DNA methylation in regulating the biological consequences of infection. Using a wide variety of strategies and techniques ranging from simple ChIP to ChIP-chip and ChIP-seq to identify histone modifications, nuclease digestion to genome wide next generation sequencing to identify nucleosome location, and bisulfite treatment to MeDIP to identify DNA methylation sites, the epigenetic regulation of these viruses is slowly becoming better understood. While the viruses may differ in significant ways from each other and cellular chromatin, the role of epigenetics appears to be relatively similar. Within the viral genome nucleosomes are organized for the expression of appropriate genes with relevant histone modifications particularly histone acetylation. DNA methylation occurs as part of the typical gene silencing during latent infection by herpesviruses. In the simple tumor viruses like the polyomaviruses, adenoviruses, and papillomaviruses, transformation of the cell occurs via integration of the virus genome such that the virus's normal regulation is disrupted. This results in the unregulated expression of critical viral genes capable of redirecting cellular gene expression. The redirected cellular expression is a consequence of either indirect epigenetic regulation where cellular signaling or transcriptional dysregulation occurs or direct epigenetic regulation where epigenetic cofactors such as histone deacetylases are targeted. In the more complex herpersviruses transformation is a consequence of the expression of the viral latency proteins and RNAs which again can have either a direct or indirect effect on epigenetic regulation of cellular expression. Nevertheless, many questions still remain with respect to the specific mechanisms underlying epigenetic regulation of the viruses and transformation. PMID:25421681

  6. MOSQUITO PATHOGENIC VIRUSES - THE LAST 20 YEARS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are several types of viral pathogens that cause disease in mosquitoes with most belonging to four major groups. The most common viruses of mosquitoes are the baculoviruses (NPVs) (Baculoviridae: Nucleopolyhedrovirus) and cytoplasmic polyhedrosis viruses (CPVs) (Reoviridae: Cypovirus). The ot...

  7. Susceptibility of common fish and chelonians to ranavirus Tucker, J. L.1, R. Brenes1, D. L. Miller1,3, T. B. Waltzek2, R. P. Wilkes3, , M. D. Brand1, J. C. Chaney1, R. Hardman1,3,

    E-print Network

    Gray, Matthew

    ranaviruses have been isolated from different ectothermic vertebrate classes; however, few studies have ectothermic vertebrate classes. Virus The challenges were conducted using FV3-like ranavirus isolates obtained from three different ectothermic hosts; fish (pallid sturgeon), turtle (Box Turtle), and amphibian

  8. Viral Quasispecies Evolution

    PubMed Central

    Sheldon, Julie; Perales, Celia

    2012-01-01

    Summary: Evolution of RNA viruses occurs through disequilibria of collections of closely related mutant spectra or mutant clouds termed viral quasispecies. Here we review the origin of the quasispecies concept and some biological implications of quasispecies dynamics. Two main aspects are addressed: (i) mutant clouds as reservoirs of phenotypic variants for virus adaptability and (ii) the internal interactions that are established within mutant spectra that render a virus ensemble the unit of selection. The understanding of viruses as quasispecies has led to new antiviral designs, such as lethal mutagenesis, whose aim is to drive viruses toward low fitness values with limited chances of fitness recovery. The impact of quasispecies for three salient human pathogens, human immunodeficiency virus and the hepatitis B and C viruses, is reviewed, with emphasis on antiviral treatment strategies. Finally, extensions of quasispecies to nonviral systems are briefly mentioned to emphasize the broad applicability of quasispecies theory. PMID:22688811

  9. Processes for managing pathogens.

    PubMed

    Godfree, Alan; Farrell, Joseph

    2005-01-01

    Wastewater contains human, animal, and plant pathogens capable of causing viral, bacterial, or parasitic infections. There are several routes whereby sewage pathogens may affect human health, including direct contact, contamination of food crops, zoonoses, and vectors. The range and numbers of pathogens in municipal wastewater vary with the level of endemic disease in the community, discharges from commercial activities, and seasonal factors. Regulations to control pathogen risk in the United States and Europe arising from land application of biosolids are based on the concept of multiple barriers to the prevention of transmission. The barriers are (i) treatment to reduce pathogen content and vector attraction, (ii) restrictions on crops grown on land to which biosolids have been applied, and (iii) minimum intervals following application and grazing or harvesting. Wastewater treatment reduces number of pathogens in the wastewater by concentrating them with the solids in the sludge. Although some treatment processes are designed specifically to inactivate pathogens, many are not, and the actual mechanisms of microbial inactivation are not fully understood for all processes. Vector attraction is reduced by stabilization (reduction of readily biodegradable material) and/or incorporation immediately following application. Concerns about health risks have renewed interest in the effects of treatment (on pathogens) and advanced treatment methods, and work performed in the United States suggests that Class A pathogen reduction can be achieved less expensively than previously thought. Effective pathogen risk management requires control to the complete chain of sludge treatment, biosolids handling and application, and post-application activities. This may be achieved by adherence to quality management systems based on hazard analysis critical control point (HACCP) principles. PMID:15647539

  10. Viral Hijackers

    NSDL National Science Digital Library

    2014-09-18

    Students learn how viruses invade host cells and hijack the hosts' cell-reproduction mechanisms in order to make new viruses, which can in turn attack additional host cells. Students also learn how the immune system responds to a viral invasion, eventually defeating the viruses—if all goes well. Finally, they consider the special case of HIV, in which the virus' host cell is a key component of the immune system itself, severely crippling it and ultimately leading to AIDS. The associated activity sets the stage for this lesson with a dramatic simulation that allows students to see for themselves how quickly a virus can spread through a population, and then challenges students to determine who the initial bearers of the virus were.

  11. Diagnostics and Discovery in Viral Hemorrhagic Fevers

    PubMed Central

    Lipkin, W. Ian; Palacios, Gustavo; Briese, Thomas

    2014-01-01

    The rate of discovery of new microbes and of new associations of microbes with health and disease is accelerating. Many factors contribute to this phenomenon including those that favor the true emergence of new pathogens as well as new technologies and paradigms that enable their detection and characterization. This chapter reviews recent progress in the field of pathogen surveillance and discovery with a focus on viral hemorrhagic fevers. PMID:19751404

  12. Viral Subversion of Nucleocytoplasmic Trafficking

    PubMed Central

    Yarbrough, Melanie L.; Mata, Miguel A.; Sakthivel, Ramanavelan; Fontoura, Beatriz M. A.

    2014-01-01

    Trafficking of proteins and RNA into and out of the nucleus occurs through the nuclear pore complex (NPC). Due to its critical function in many cellular processes, the NPC and transport factors are common targets of several viruses that disrupt key constituents of the machinery to facilitate viral replication. Many viruses such as poliovirus and severe acute respiratory syndrome (SARS) virus inhibit protein import into the nucleus, while viruses such as influenza A virus target and disrupt host mRNA nuclear export. Current evidence indicates that these viruses may employ such strategies to avert the host immune response. Conversely, many viruses co-opt nucleocytoplasmic trafficking to facilitate transport of viral RNAs. Since viral proteins interact with key regulators of the host nuclear transport machinery, viruses have served as invaluable tools of discovery that led to the identification of novel constituents of nuclear transport pathways. In addition, this review explores the importance of nucleocytoplasmic trafficking to viral pathogenesis as these studies revealed new antiviral therapeutic strategies and exposed previously unknown cellular mechanisms. Further understanding of nuclear transport pathways will determine whether such therapeutics will be useful treatments for important human pathogens. PMID:24289861

  13. Detection of 11 Common Viral and Bacterial Pathogens Causing Community-Acquired Pneumonia or Sepsis in Asymptomatic Patients by Using a Multiplex Reverse Transcription-PCR Assay with Manual (Enzyme Hybridization) or Automated (Electronic Microarray) Detection

    Microsoft Academic Search

    Swati Kumar; Lihua Wang; Jiang Fan; Andrea Kraft; Michael E. Bose; Sagarika Tiwari; Meredith Van Dyke; Robert Haigis; Tingquo Luo; Madhushree Ghosh; Huong Tang; Marjan Haghnia; Elizabeth L. Mather; William G. Weisburg; Kelly J. Henrickson

    2008-01-01

    Community-acquired pneumonia (CAP) and sepsis are important causes of morbidity and mortality. We describe the development of two molecular assays for the detection of 11 common viral and bacterial agents of CAP and sepsis: influenza virus A, influenza virus B, respiratory syncytial virus A (RSV A), RSV B, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, Legionella micdadei, Bordetella pertussis, Staph- ylococcus

  14. Native microbiota shape insect vector competence for human pathogens

    PubMed Central

    Cirimotich, Chris M.; Ramirez, Jose L.; Dimopoulos, George

    2012-01-01

    Summary The resident microbiota of insect vectors can impede transmission of human pathogens. Recent studies have highlighted the capacity of endogenous bacteria to decrease viral and parasitic infections in mosquito and tsetse fly vectors by activating their immune responses or directly inhibiting pathogen development. These microbes may prove effective agents for manipulating the vector competence of malaria and other important human pathogens. PMID:22018231

  15. Assembly of viral genomes from metagenomes

    PubMed Central

    Smits, Saskia L.; Bodewes, Rogier; Ruiz-Gonzalez, Aritz; Baumgärtner, Wolfgang; Koopmans, Marion P.; Osterhaus, Albert D. M. E.; Schürch, Anita C.

    2014-01-01

    Viral infections remain a serious global health issue. Metagenomic approaches are increasingly used in the detection of novel viral pathogens but also to generate complete genomes of uncultivated viruses. In silico identification of complete viral genomes from sequence data would allow rapid phylogenetic characterization of these new viruses. Often, however, complete viral genomes are not recovered, but rather several distinct contigs derived from a single entity are, some of which have no sequence homology to any known proteins. De novo assembly of single viruses from a metagenome is challenging, not only because of the lack of a reference genome, but also because of intrapopulation variation and uneven or insufficient coverage. Here we explored different assembly algorithms, remote homology searches, genome-specific sequence motifs, k-mer frequency ranking, and coverage profile binning to detect and obtain viral target genomes from metagenomes. All methods were tested on 454-generated sequencing datasets containing three recently described RNA viruses with a relatively large genome which were divergent to previously known viruses from the viral families Rhabdoviridae and Coronaviridae. Depending on specific characteristics of the target virus and the metagenomic community, different assembly and in silico gap closure strategies were successful in obtaining near complete viral genomes. PMID:25566226

  16. 51www.wildlife.org The Wildlife Society The Rise of Ranavirus

    E-print Network

    Gray, Matthew

    . Miller an eMeRGinG patHoGen tHReatenS eCtotHeRMiC VeRteBRateS R anaviruses have been called "cold ectothermic vertebrate classes (amphibians, reptiles, and fish). Experi- ments have also demonstrated. 1965), yet their role in widespread die-offs of ectothermic ver- tebrates wasn't realized until

  17. Genomic sequence of a ranavirus (family Iridoviridae) associated with salamander mortalities in North America

    E-print Network

    declines, and an iridovirus and a chytrid fungus are the primary pathogens associated with amphibian 2003; accepted 1 August 2003 Abstract Disease is among the suspected causes of amphibian population infections have on amphibian and fish populations, ATV/RRV sequence information will allow the design

  18. Complete Genome Sequence of the European Sheatfish Virus

    PubMed Central

    Mavian, Carla; López-Bueno, Alberto; Fernández Somalo, María Pilar; Alcamí, Antonio

    2012-01-01

    Viral diseases are an increasing threat to the thriving aquaculture industry worldwide. An emerging group of fish pathogens is formed by several ranaviruses, which have been isolated at different locations from freshwater and seawater fish species since 1985. We report the complete genome sequence of European sheatfish ranavirus (ESV), the first ranavirus isolated in Europe, which causes high mortality rates in infected sheatfish (Silurus glanis) and in other species. Analysis of the genome sequence shows that ESV belongs to the amphibian-like ranaviruses and is closely related to the epizootic hematopoietic necrosis virus (EHNV), a disease agent geographically confined to the Australian continent and notifiable to the World Organization for Animal Health. PMID:22570241

  19. Sensing viral invasion by RIG-I like receptors.

    PubMed

    Yoo, Ji-Seung; Kato, Hiroki; Fujita, Takashi

    2014-08-01

    Cellular responses to pathogen invasion are crucial for maintaining cell homeostasis and survival. The interferon (IFN) system is one of the most effective cellular responses to viral intrusion in mammals. Viral recognition by innate immune sensors activates the antiviral IFN system. Retinoic acid-inducible gene I (RIG-I) like receptors (RLRs) are DExD/H box RNA helicases that sense viral invasion. RLRs recognize cytoplasmic viral RNAs and trigger antiviral responses, resulting in production of type I IFN and inflammatory cytokines. Unique and common sensing mechanisms among RLRs have been reported. In this review, recent progress in the understanding of antiviral responses by RLRs is summarized and discussed. PMID:24968321

  20. Broad-Spectrum Drugs Against Viral Agents

    PubMed Central

    Christopher, Mary E.; Wong, Jonathan P.

    2008-01-01

    Development of antivirals has focused primarily on vaccines and on treatments for specific viral agents. Although effective, these approaches may be limited in situations where the etiologic agent is unknown or when the target virus has undergone mutation, recombination or reassortment. Augmentation of the innate immune response may be an effective alternative for disease amelioration. Nonspecific, broad-spectrum immune responses can be induced by double-stranded (ds)RNAs such as poly (ICLC), or oligonucleotides (ODNs) containing unmethylated deocycytidyl-deoxyguanosinyl (CpG) motifs. These may offer protection against various bacterial and viral pathogens regardless of their genetic makeup, zoonotic origin or drug resistance. PMID:19325820

  1. [Cell analogs of viral proteins].

    PubMed

    Blinov, V M; Ga?sler, V; Krasnov, G S; Shargunov, A V; Shurdov, M A; Zverev, V V

    2014-01-01

    Horizontal transfer of genes between viruses and their hosts played an important role in the evolution of various eukaryotes including contemporary mammals as well as the pathogens themselves. Elements of viruses of various types can be found in the genome of animals. Endogenous retroviral elements composing up to 8% of human genome length not only determine its high flexibility and rapid adaptation potential. Many of virus genes such as Fv1, Lv1, Lv2 being analogues of capsid and other proteins determine effective suppression of viral replication after cell penetration by the causative agent. Introduction of these elements into genome of a wide variety of animals from fish to primates could have taken place against the background of global natural cataclysms of viral origin. Integration of retrovirus genes coding surface glycoproteins with immunosuppressing domains into genetic apparatus of animals served as an impetus to the development of viviparity and spread ofplacental mammals. Their cell analogs syncytins perform a dual function: take direct part in the formation of syncytiotrophoblast layer of placenta and ensure tolerance of immune system of mother to embryo. The acquisition of cell genes by viruses also played an important role in their evolution: various interleukins and other modulators of immune response introduced into viral genome from cell genetic apparatus became one of the most important factors of pathogenicity of a wide variety of causative agents including poxviruses, cytomegalovirus, Epstein-Barr virus and many others. Evolutionary pathways of the virus and host are thus inseparable from each other, and character of one of these directions is largely dictated by the vector of another. PMID:25051706

  2. Sensitive Detection of Viral Transcripts in Human Tumor Transcriptomes

    PubMed Central

    Schelhorn, Sven-Eric; Fischer, Matthias; Tolosi, Laura; Altmüller, Janine; Nürnberg, Peter; Pfister, Herbert; Lengauer, Thomas; Berthold, Frank

    2013-01-01

    In excess of % of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses. We have developed a novel computational approach for detecting viral transcripts in human cancers that takes the aforementioned confounding factors into account and is applicable to a wide variety of viruses and tumors. We apply the approach to conducting the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The diverse clinical progression of this disease as well as related epidemiological and virological findings are highly suggestive of a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently contested. We mapped transcriptomes of neuroblastoma as well as positive and negative controls to the human and all known viral genomes in order to detect both known and unknown viruses. Analysis of controls, comparisons with related methods, and statistical estimates demonstrate the high sensitivity of our approach. Detailed investigation of putative viral transcripts within neuroblastoma samples did not provide evidence for the existence of any known human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts did not result in expression signatures associated with novel human pathogens. While confounding factors such as sample dilution or viral clearance in progressed tumors may mask viral cofactors in the data, in principle, this is rendered less likely by the high sensitivity of our approach and the number of biological replicates analyzed. Therefore, our results suggest that frequent viral cofactors of metastatic neuroblastoma are unlikely. PMID:24098097

  3. Clinical applications of pathogen phylogenies.

    PubMed

    Hartfield, Matthew; Murall, Carmen Lía; Alizon, Samuel

    2014-07-01

    Innovative sequencing techniques now allow the routine access of whole genomes of pathogens, generating vast amounts of data. Phylogenetic trees are a common method for synthesizing this information. Unfortunately, these trees are often seen only as a visual support to guide researchers, thus neglecting the value of employing phylogenetic techniques to perform hypothesis testing on clinical questions. These include investigating how a pathogen spreads within a patient, or whether the infection severity (often measured by virus load) is controlled by viral genetics. Advances in methodology mean the time is ripe for combining phylogenies with clinical data to better understand and fight infectious diseases. PMID:24794010

  4. Genomic Basis of Plant Pathogen Suppression by Biocontrol Pseudomonas Species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Various plant commensal bacterial species, which naturally colonize the plant rhizosphere, are able to suppress fungal, bacterial, viral and even insect plant pathogens. These biocontrol activities are elicited primarily through the production of secreted exoenzymes and secondary metabolites that ma...

  5. Current Status of Deltabaculoviruses, Cypoviruses and Chloriridoviruses Pathogenic for Mosquitoes.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are a variety of viral pathogens that cause disease in mosquitoes with most belonging to three major groups. The most common viruses of mosquitoes are the baculoviruses (DBVs) (Baculoviridae: Deltabaculovirus), cytoplasmic polyhedrosis viruses (CPVs) (Reoviridae: Cypovirus) and the iridovirus...

  6. ADEQUACY OF DISINFECTION FOR CONTROL OF NEWLY RECOGNIZED WATERBORNE PATHOGENS

    EPA Science Inventory

    Agents recently recognized as causes or potential causes of waterborne outbreaks include pathogenic bacteria (Campylobacter jejuni, Yersinia enterocoliticia), viruses (rotavirus, Norwalk virus and other poorly defined viral agents) and Giardia lamblia, a protozoan agent. Although...

  7. The structure of the RNA-dependent RNA polymerase from bovine viral diarrhea virus establishes the role

    E-print Network

    Rossmann, Michael G.

    The structure of the RNA-dependent RNA polymerase from bovine viral diarrhea virus establishes The bovine viral diarrhea virus (BVDV) RNA-dependent RNA poly- merase can initiate RNA replication by a de bovine viral diarrhea virus (BVDV)]. Pestiviruses are animal pathogens of major importance, particularly

  8. Tobacco Mosaic Virus Infection Results in an Increase in Recombination Frequency and Resistance to Viral, Bacterial, and Fungal Pathogens in the Progeny of Infected Tobacco Plants1[C][W][OA

    PubMed Central

    Kathiria, Palak; Sidler, Corinne; Golubov, Andrey; Kalischuk, Melanie; Kawchuk, Lawrence M.; Kovalchuk, Igor

    2010-01-01

    Our previous experiments showed that infection of tobacco (Nicotiana tabacum) plants with Tobacco mosaic virus (TMV) leads to an increase in homologous recombination frequency (HRF). The progeny of infected plants also had an increased rate of rearrangements in resistance gene-like loci. Here, we report that tobacco plants infected with TMV exhibited an increase in HRF in two consecutive generations. Analysis of global genome methylation showed the hypermethylated genome in both generations of plants, whereas analysis of methylation via 5-methyl cytosine antibodies demonstrated both hypomethylation and hypermethylation. Analysis of the response of the progeny of infected plants to TMV, Pseudomonas syringae, or Phytophthora nicotianae revealed a significant delay in symptom development. Infection of these plants with TMV or P. syringae showed higher levels of induction of PATHOGENESIS-RELATED GENE1 gene expression and higher levels of callose deposition. Our experiments suggest that viral infection triggers specific changes in progeny that promote higher levels of HRF at the transgene and higher resistance to stress as compared with the progeny of unstressed plants. However, data reported in these studies do not establish evidence of a link between recombination frequency and stress resistance. PMID:20498336

  9. Syntheses of immunodominant peptide regions of hepatitis C viral pathogens using PS-BDODMA resin: a single peptide derived from the conserved domain (E2/NS1) was highly effective in detecting anti-HCV antibodies.

    PubMed

    Kumar, K S; Roice, M; Sasikumar, P G; Poduri, C D; Sugunan, V S; Rajasekharan Pillai, V N; Das, M R

    2001-02-01

    Peptides were synthesized with very high purity and yield on a highly solvating copolymer of 1,4-butanediol dimethacrylate cross-linked polystyrene support (PS-BDODMA). The polymer was synthesized by radical aqueous suspension polymerization using toluene as the diluent and 1% polyvinyl alcohol as the suspension stabilizer. The supports were highly resistant to various chemical reagents and solvents that are frequently used in polypeptide synthesis. The peptides synthesized on this support were designed from the core (C), envelope (E1 and E2) and nonstructural protein (NS1-NS5) regions of the prototype hepatitis C viral (HCV) polyprotein, and were used to develop a peptide-based immunoassay (PBEIA) for the detection of HCV antibodies. The purity of these peptides was tested by HPLC. Peptide identity was confirmed by amino acid analysis and MALDI-TOF-MS. A single peptide chosen from a conserved area (E2/NS1) at the C-terminus of the hypervariable region (HVRI) was found to be sufficient for effective and reliable diagnosis of HCV infection in infected individuals, as well as also apparently healthy individuals. The CD spectrum of the peptide shows no preference for any ordered secondary structure. When used, peptide mixtures from various protein regions of HCV reduced the sensitivity and reliability of the diagnosis partly because of epitope masking. PMID:11168897

  10. Fulminant viral hepatitis.

    PubMed

    Jayakumar, Saumya; Chowdhury, Raiyan; Ye, Carrie; Karvellas, Constantine J

    2013-07-01

    Acute liver failure (ALF) is a condition wherein the previously healthy liver rapidly deteriorates, resulting in jaundice, encephalopathy, and coagulopathy. There are approximately 2000 cases per year of ALF in the United States. Viral causes (fulminant viral hepatitis [FVH]) are the predominant cause of ALF in developing countries. Given the ease of spread of viral hepatitis and the high morbidity and mortality associated with ALF, a systematic approach to the diagnosis and treatment of FVH is required. In this review, the authors describe the viral causes of ALF and review the intensive care unit management of patients with FVH. PMID:23830658

  11. Raw Sewage Harbors Diverse Viral Populations

    PubMed Central

    Cantalupo, Paul G.; Calgua, Byron; Zhao, Guoyan; Hundesa, Ayalkibet; Wier, Adam D.; Katz, Josh P.; Grabe, Michael; Hendrix, Roger W.; Girones, Rosina; Wang, David; Pipas, James M.

    2011-01-01

    ABSTRACT At this time, about 3,000 different viruses are recognized, but metagenomic studies suggest that these viruses are a small fraction of the viruses that exist in nature. We have explored viral diversity by deep sequencing nucleic acids obtained from virion populations enriched from raw sewage. We identified 234 known viruses, including 17 that infect humans. Plant, insect, and algal viruses as well as bacteriophages were also present. These viruses represented 26 taxonomic families and included viruses with single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), positive-sense ssRNA [ssRNA(+)], and dsRNA genomes. Novel viruses that could be placed in specific taxa represented 51 different families, making untreated wastewater the most diverse viral metagenome (genetic material recovered directly from environmental samples) examined thus far. However, the vast majority of sequence reads bore little or no sequence relation to known viruses and thus could not be placed into specific taxa. These results show that the vast majority of the viruses on Earth have not yet been characterized. Untreated wastewater provides a rich matrix for identifying novel viruses and for studying virus diversity. Importance At this time, virology is focused on the study of a relatively small number of viral species. Specific viruses are studied either because they are easily propagated in the laboratory or because they are associated with disease. The lack of knowledge of the size and characteristics of the viral universe and the diversity of viral genomes is a roadblock to understanding important issues, such as the origin of emerging pathogens and the extent of gene exchange among viruses. Untreated wastewater is an ideal system for assessing viral diversity because virion populations from large numbers of individuals are deposited and because raw sewage itself provides a rich environment for the growth of diverse host species and thus their viruses. These studies suggest that the viral universe is far more vast and diverse than previously suspected. PMID:21972239

  12. A comparison of rapid and conventional measures of indicator bacteria as predictors of waterborne protozoan pathogen presence and density

    E-print Network

    Illinois at Chicago, University of

    protozoan pathogen presence and density Samuel Dorevitch,*abc Mary Doi,b Fu-Chih Hsu,ad King-Teh Lin. Introduction A variety of bacterial, viral, and protozoan pathogens have been identified as causes

  13. Viral Disease Networks?

    NASA Astrophysics Data System (ADS)

    Gulbahce, Natali; Yan, Han; Vidal, Marc; Barabasi, Albert-Laszlo

    2010-03-01

    Viral infections induce multiple perturbations that spread along the links of the biological networks of the host cells. Understanding the impact of these cascading perturbations requires an exhaustive knowledge of the cellular machinery as well as a systems biology approach that reveals how individual components of the cellular system function together. Here we describe an integrative method that provides a new approach to studying virus-human interactions and its correlations with diseases. Our method involves the combined utilization of protein - protein interactions, protein -- DNA interactions, metabolomics and gene - disease associations to build a ``viraldiseasome''. By solely using high-throughput data, we map well-known viral associated diseases and predict new candidate viral diseases. We use microarray data of virus-infected tissues and patient medical history data to further test the implications of the viral diseasome. We apply this method to Epstein-Barr virus and Human Papillomavirus and shed light into molecular development of viral diseases and disease pathways.

  14. Viral diseases of marine invertebrates

    NASA Astrophysics Data System (ADS)

    Johnson, P. T.

    1984-03-01

    Approximately 40 viruses are known from marine sponges; turbellarian and monogenetic flatworms; cephalopod, bivalve, and gastropod mollusks; nereid polychaetes; and isopod and decapod crustaceans. Most of the viruses can be tentatively assigned to the Herpesviridae, Baculoviridae, Iridoviridae, Adenoviridae, Papovaviridae, Reoviridae, “Birnaviridae”, Bunyaviridae, Rhabdoviridae, and Picornaviridae. Viruslike particles found in oysters might be representatives of the Togaviridae and Retroviridae. Enveloped single-stranded RNA viruses from crustaceans have developmental and morphological characteristics intermediate between families, and some show evidence of relationships to the Paramyxoviridae as well as the Bunyaviridae or Rhabdoviridae. Certain small viruses of shrimp cannot be assigned, even tentatively, to a particular family. Some viruses cause disease in wild and captive hosts, others are associated with disease states but may not be primary instigators, and many occur in apparently normal animals. The frequency of viral disease in natural populations of marine invertebrates is unknown. Several viruses that cause disease in captive animals, with or without experimental intervention, have also been found in diseased wild hosts, including herpeslike viruses of crabs and oysters, iridovirus of octopus, and reolike and bunyalike viruses of crabs. Iridolike viruses have been implicated in massive mortalities of cultured oysters. Baculoviruses, and IHHN virus, which is of uncertain affinities, cause economically damaging diseases in cultured penaeid shrimp. Double or multiple viral infection is common in crabs. For example, a reolike virus and associated rhabdolike virus act synergistically to cause paralytic and fatal disease in Callinectes sapidus. Information on host range, most susceptible stage, and viral latency is available only for viruses of shrimp. One baculovirus attacks five species of New World penaeid shrimp. IHHN virus infects three species of Penaeus and causes catastrophic mortalities in P. stylirostris, but usually exhibits only inapparent infection in P. vannamei. Some shrimp viruses apparently are latent in larvae, causing disease only when shrimp have reached the postlarval or juvenile stages. Others are equally or more pathogenic in larvae. Studies of shrimp viruses and iridovirus-associated disease in cultured oysters point up the need for rapid and accurate diagnostic methods. Until appropriate cell cultures from marine invertebrates are devised, the viral identifications necessary for understanding of epizootiology, rapid containment of epizootics in cultured animals, and decisions regarding introductions of exotic species will be difficult or impossible.

  15. Evaluation of Potential Indicators of Viral Contamination in Shellfish and Their Applicability to Diverse Geographical Areas

    Microsoft Academic Search

    M. Formiga-Cruz; A. K. Allard; A.-C. Conden-Hansson; K. Henshilwood; B. E. Hernroth; J. Jofre; D. N. Lees; F. Lucena; M. Papapetropoulou; R. E. Rangdale; A. Tsibouxi; A. Vantarakis; R. Girones

    2003-01-01

    The distribution of the concentration of potential indicators of fecal viral pollution in shellfish was analyzed under diverse conditions over 18 months in diverse geographical areas. These microorganisms have been evaluated in relation to contamination by human viral pathogens detected in parallel in the analyzed shellfish samples. Thus, significant shellfish-growing areas from diverse countries in the north and south of

  16. The effect of infection with bovine viral diarrhea virus on the fertility of Swiss dairy cattle

    Microsoft Academic Search

    J. Rüfenacht; P. Schaller; L. Audigé; B. Knutti; U. Küpfer; E. Peterhans

    2001-01-01

    Bovine viral diarrhea virus is a major cattle pathogen with a worldwide distribution. Animals may be infected with BVD virus transiently or persistently. Transient infection leads to protective immunity. Persistent infection is unique because it is associated with an immunotolerance that is specific to the infecting strain of BVD virus. Persistent infection results from viral invasion of fetuses between the

  17. Co-existence of genetically and antigenically diverse bovine viral diarrhoea viruses in an endemic situation

    Microsoft Academic Search

    Claudia Bachofen; Hanspeter Stalder; Ueli Braun; Monika Hilbe; Felix Ehrensperger; Ernst Peterhans

    2008-01-01

    Bovine viral diarrhoea virus (BVDV) is an important cattle pathogen that causes acute or persistent infections. These are associated with immunotolerance to the viral strain persisting in animals that became infected early in their intrauterine development. To this date, the epidemiology of BVD in Switzerland runs virtually undisturbed by control measures such as restrictions on animal traffic or vaccination. Here,

  18. Correlates of viral richness in bats (order Chiroptera).

    PubMed

    Turmelle, Amy S; Olival, Kevin J

    2009-12-01

    Historic and contemporary host ecology and evolutionary dynamics have profound impacts on viral diversity, virulence, and associated disease emergence. Bats have been recognized as reservoirs for several emerging viral pathogens, and are unique among mammals in their vagility, potential for long-distance dispersal, and often very large, colonial populations. We investigate the relative influences of host ecology and population genetic structure for predictions of viral richness in relevant reservoir species. We test the hypothesis that host geographic range area, distribution, population genetic structure, migratory behavior, International Union for Conservation of Nature and Natural Resources (IUCN) threat status, body mass, and colony size, are associated with known viral richness in bats. We analyze host traits and viral richness in a generalized linear regression model framework, and include a correction for sampling effort and phylogeny. We find evidence that sampling effort, IUCN status, and population genetic structure correlate with observed viral species richness in bats, and that these associations are independent of phylogeny. This study is an important first step in understanding the mechanisms that promote viral richness in reservoir species, and may aid in predicting the emergence of viral zoonoses from bats. PMID:20049506

  19. The Fecal Viral Flora of Wild Rodents

    PubMed Central

    Phan, Tung G.; Kapusinszky, Beatrix; Wang, Chunlin; Rose, Robert K.; Lipton, Howard L.; Delwart, Eric L.

    2011-01-01

    The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat) collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae, Astroviridae, Parvoviridae, Papillomaviridae, Adenoviridae, and Coronaviridae. Seventeen small circular DNA genomes containing one or two replicase genes distantly related to the Circoviridae representing several potentially new viral families were characterized. In the Picornaviridae family two new candidate genera as well as a close genetic relative of the human pathogen Aichi virus were characterized. Fragments of the first mouse sapelovirus and picobirnaviruses were identified and the first murine astrovirus genome was characterized. A mouse papillomavirus genome and fragments of a novel adenovirus and adenovirus-associated virus were also sequenced. The next largest fraction of the rodent fecal virome was related to insect viruses of the Densoviridae, Iridoviridae, Polydnaviridae, Dicistroviriade, Bromoviridae, and Virgaviridae families followed by plant virus-related sequences in the Nanoviridae, Geminiviridae, Phycodnaviridae, Secoviridae, Partitiviridae, Tymoviridae, Alphaflexiviridae, and Tombusviridae families reflecting the largely insect and plant rodent diet. Phylogenetic analyses of full and partial viral genomes therefore revealed many previously unreported viral species, genera, and families. The close genetic similarities noted between some rodent and human viruses might reflect past zoonoses. This study increases our understanding of the viral diversity in wild rodents and highlights the large number of still uncharacterized viruses in mammals. PMID:21909269

  20. HIV Viral Load

    MedlinePLUS

    ... that an HIV viral load test detects HIV RNA. What is an HIV DNA test? The HIV ... HIV-1-Infected Adults and Adolescents, Plasma HIV RNA Testing. AIDSinfo On-line information]. Available online through ...

  1. Viral infections during pregnancy.

    PubMed

    Silasi, Michelle; Cardenas, Ingrid; Kwon, Ja-Young; Racicot, Karen; Aldo, Paula; Mor, Gil

    2015-03-01

    Viral infections during pregnancy have long been considered benign conditions with a few notable exceptions, such as herpes virus. The recent Ebola outbreak and other viral epidemics and pandemics show how pregnant women suffer worse outcomes (such as preterm labor and adverse fetal outcomes) than the general population and non-pregnant women. New knowledge about the ways the maternal-fetal interface and placenta interact with the maternal immune system may explain these findings. Once thought to be 'immunosuppressed', the pregnant woman actually undergoes an immunological transformation, where the immune system is necessary to promote and support the pregnancy and growing fetus. When this protection is breached, as in a viral infection, this security is weakened and infection with other microorganisms can then propagate and lead to outcomes, such as preterm labor. In this manuscript, we review the major viral infections relevant to pregnancy and offer potential mechanisms for the associated adverse pregnancy outcomes. PMID:25582523

  2. Viral membrane fusion

    Microsoft Academic Search

    Stephen C Harrison

    2008-01-01

    Infection by viruses having lipid-bilayer envelopes proceeds through fusion of the viral membrane with a membrane of the target cell. Viral 'fusion proteins' facilitate this process. They vary greatly in structure, but all seem to have a common mechanism of action, in which a ligand-triggered, large-scale conformational change in the fusion protein is coupled to apposition and merger of the

  3. Optimal viral production

    Microsoft Academic Search

    Daniel Coombs; Michael A. Gilchrist; Jerome Percus; Alan S. Perelson

    2003-01-01

    Viruses reproduce by multiplying within host cells. The reproductive fitness of a virus is proportional to the number of offspring\\u000a it can produce during the lifetime of the cell it infects. If viral production rates are independent of cell death rate, then\\u000a one expects natural selection will favor viruses that maximize their production rates. However, if increases in the viral

  4. Viral suppressors of RNA-based viral immunity: Host targets

    PubMed Central

    Wu, Qingfa; Wang, Xianbing

    2010-01-01

    Discovery of diverse plant and animal viral proteins as suppressors of RNA silencing has provided strong support for an RNA-based viral immunity (RVI), which is now known to specifically destroy viral RNAs by RNA interference in fungi, plants and invertebrates. Here we review several recent studies that have revealed new mechanistic insights into plant and insect viral suppressors of RVI or suggested a role for RNA silencing suppression during mammalian viral infection. PMID:20638637

  5. NCBI Viral Genomes Resource

    PubMed Central

    Brister, J. Rodney; Ako-adjei, Danso; Bao, Yiming; Blinkova, Olga

    2015-01-01

    Recent technological innovations have ignited an explosion in virus genome sequencing that promises to fundamentally alter our understanding of viral biology and profoundly impact public health policy. Yet, any potential benefits from the billowing cloud of next generation sequence data hinge upon well implemented reference resources that facilitate the identification of sequences, aid in the assembly of sequence reads and provide reference annotation sources. The NCBI Viral Genomes Resource is a reference resource designed to bring order to this sequence shockwave and improve usability of viral sequence data. The resource can be accessed at http://www.ncbi.nlm.nih.gov/genome/viruses/ and catalogs all publicly available virus genome sequences and curates reference genome sequences. As the number of genome sequences has grown, so too have the difficulties in annotating and maintaining reference sequences. The rapid expansion of the viral sequence universe has forced a recalibration of the data model to better provide extant sequence representation and enhanced reference sequence products to serve the needs of the various viral communities. This, in turn, has placed increased emphasis on leveraging the knowledge of individual scientific communities to identify important viral sequences and develop well annotated reference virus genome sets. PMID:25428358

  6. NCBI viral genomes resource.

    PubMed

    Brister, J Rodney; Ako-Adjei, Danso; Bao, Yiming; Blinkova, Olga

    2015-01-01

    Recent technological innovations have ignited an explosion in virus genome sequencing that promises to fundamentally alter our understanding of viral biology and profoundly impact public health policy. Yet, any potential benefits from the billowing cloud of next generation sequence data hinge upon well implemented reference resources that facilitate the identification of sequences, aid in the assembly of sequence reads and provide reference annotation sources. The NCBI Viral Genomes Resource is a reference resource designed to bring order to this sequence shockwave and improve usability of viral sequence data. The resource can be accessed at http://www.ncbi.nlm.nih.gov/genome/viruses/ and catalogs all publicly available virus genome sequences and curates reference genome sequences. As the number of genome sequences has grown, so too have the difficulties in annotating and maintaining reference sequences. The rapid expansion of the viral sequence universe has forced a recalibration of the data model to better provide extant sequence representation and enhanced reference sequence products to serve the needs of the various viral communities. This, in turn, has placed increased emphasis on leveraging the knowledge of individual scientific communities to identify important viral sequences and develop well annotated reference virus genome sets. PMID:25428358

  7. Microvesicles and Viral Infection?

    PubMed Central

    Meckes, David G.; Raab-Traub, Nancy

    2011-01-01

    Cells secrete various membrane-enclosed microvesicles from their cell surface (shedding microvesicles) and from internal, endosome-derived membranes (exosomes). Intriguingly, these vesicles have many characteristics in common with enveloped viruses, including biophysical properties, biogenesis, and uptake by cells. Recent discoveries describing the microvesicle-mediated intercellular transfer of functional cellular proteins, RNAs, and mRNAs have revealed additional similarities between viruses and cellular microvesicles. Apparent differences include the complexity of viral entry, temporally regulated viral expression, and self-replication proceeding to infection of new cells. Interestingly, many virally infected cells secrete microvesicles that differ in content from their virion counterparts but may contain various viral proteins and RNAs. For the most part, these particles have not been analyzed for their content or functions during viral infection. However, early studies of microvesicles (L-particles) secreted from herpes simplex virus-infected cells provided the first evidence of microvesicle-mediated intercellular communication. In the case of Epstein-Barr virus, recent evidence suggests that this tumorigenic herpesvirus also utilizes exosomes as a mechanism of cell-to-cell communication through the transfer of signaling competent proteins and functional microRNAs to uninfected cells. This review focuses on aspects of the biology of microvesicles with an emphasis on their potential contributions to viral infection and pathogenesis. PMID:21976651

  8. Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

    USGS Publications Warehouse

    Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

    2012-01-01

    Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.

  9. Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

    PubMed Central

    Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

    2012-01-01

    Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed. PMID:22310066

  10. Development and evaluation of a replicon particle vaccine expressing the E2 glycoprotein of bovine viral diarrhea virus (BVDV) in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus is one of the most significant and costly viral pathogens of cattle worldwide. Alphavirus-derived replicon particles have been shown to be safe and highly effective vaccine vectors against a variety of human and veterinary pathogens. Replicon particles are non-propagating...

  11. Black leaf streak and viral leaf streak: New banana diseases in East Africa

    Microsoft Academic Search

    A. J. Dabek; J. M. Waller

    1990-01-01

    Black leaf streak, caused by Mycosphaerella fijiensis a virulent pathogen of bananas and plantains, is recorded from Zanzibar. This is the first record of this important pathogen from East Africa. Viral leaf streak of bananas is also identified from Zanzibar. The presence of panama disease and high infestations of root nematode are also noted.

  12. [Bovine viral diarrhea control in Russian Federation].

    PubMed

    Guliukin, M I; Iurov, K P; Glotov, A G; Donchenko, N A

    2013-01-01

    Bovine viral diarrhea (BVD) is one of the greatest challenges for breeding and commercial livestock. It is characterized by lesions of the respiratory and gastrointestinal tract, abortion, infertility, immune deficiency, and persistence of the pathogen. In this work, a set of measures for the rehabilitation and prevention of BVD in cattle is described. It includes the data of the literature, guidance documents for the diagnosis and control of BVD adopted by OIE, EU countries, USA, as well as the results of this research. PMID:24772640

  13. 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

  14. Viral RNA extraction for in-the-field analysis

    PubMed Central

    Zhong, Jiang F.; Weiner, Leslie P.; Burke, Kathy; Taylor, Clive R.

    2012-01-01

    Retroviruses encode their genetic information with RNA molecules, and have a high genomic recombination rate which allows them to mutate more rapidly, thereby posting a higher risk to humans. One important way to help combat a pandemic of viral infectious diseases is early detection before large scale outbreaks occur. The polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) have been used to identify precisely different strains of some very closely related pathogens. However, isolation and detection of viral RNA in the field are difficult due to the unstable nature of viral RNA molecules. Consequently, performing in-the-field nucleic acid analysis to monitor the spread of viruses is financially and technologically challenging in remote and underdeveloped regions that are high-risk areas for outbreaks. A simplified rapid viral RNA extraction method is reported to meet the requirements for in-the-field viral RNA extraction and detection. The ability of this device to perform viral RNA extraction with subsequent RT-PCR detection of retrovirus is demonstrated. This inexpensive device has the potential to be distributed on a large scale to underdeveloped regions for early detection of retrovirus, with the possibility of reducing viral pandemic events. PMID:17548117

  15. Modeling Viral Capsid Assembly

    PubMed Central

    2014-01-01

    I present a review of the theoretical and computational methodologies that have been used to model the assembly of viral capsids. I discuss the capabilities and limitations of approaches ranging from equilibrium continuum theories to molecular dynamics simulations, and I give an overview of some of the important conclusions about virus assembly that have resulted from these modeling efforts. Topics include the assembly of empty viral shells, assembly around single-stranded nucleic acids to form viral particles, and assembly around synthetic polymers or charged nanoparticles for nanotechnology or biomedical applications. I present some examples in which modeling efforts have promoted experimental breakthroughs, as well as directions in which the connection between modeling and experiment can be strengthened. PMID:25663722

  16. Optimal viral production.

    PubMed

    Coombs, Daniel; Gilchrist, Michael A; Percus, Jerome; Perelson, Alan S

    2003-11-01

    Viruses reproduce by multiplying within host cells. The reproductive fitness of a virus is proportional to the number of offspring it can produce during the lifetime of the cell it infects. If viral production rates are independent of cell death rate, then one expects natural selection will favor viruses that maximize their production rates. However, if increases in the viral production rate lead to an increase in the cell death rate, then the viral production rate that maximizes fitness may be less than the maximum. Here we pose the question of how fast should a virus replicate in order to maximize the number of progeny virions that it produces. We present a general mathematical framework for studying problems of this type, which may be adapted to many host-parasite systems, and use it to examine the optimal virus production scheduling problem from the perspective of the virus. PMID:14607286

  17. Viral encephalitis and epilepsy.

    PubMed

    Misra, Usha Kant; Tan, Chong Tin; Kalita, Jayantee

    2008-08-01

    Viral encephalitis presents with seizures not only in the acute stage but also increases the risk of late unprovoked seizures and epilepsy. Acute symptomatic and late unprovoked seizures in different viral encephalitides are reviewed here. Among the sporadic viral encephalitides, Herpes simplex encephalitis (HSE) is perhaps most frequently associated with epilepsy, which may often be severe. Seizures may be the presenting feature in 50% patients with HSE because of involvement of the highly epileptogenic frontotemporal cortex. The occurrence of seizures in HSE is associated with poor prognosis. In addition, chronic and relapsing forms of HSE have been described and these may be associated with antiepileptic drug-resistant seizures. Among the epidemic (usually due to flaviviruses) viral encephalitides, Japanese encephalitis (JE) is most common and is associated with acute symptomatic seizures, especially in children. The reported frequency of acute symptomatic seizures in JE is 7-46%. Encephalitis due to other flaviviruses such as equine, St. Louis, and West Nile viruses may also manifest with acute symptomatic seizures. In Nipah virus encephalitis, seizures are more common in relapsed and late-onset encephalitis in comparison to acute encephalitis (4% vs. 1.8%). Other viruses like measles, varicella, mumps, influenza, and entero-viruses may cause seizures depending on the area of brain involved. There is no comprehensive data regarding late unprovoked seizures in different viral encephalitides. Prospective studies are required to document the risk of late unprovoked seizures and epilepsy following viral encephalitis due to different viruses as well as to determine the clinical characteristics, course, and outcome of post-encephalitic epilepsy. PMID:18754956

  18. Ranaviruses in European reptiles

    E-print Network

    Gray, Matthew

    · Necrotizing stomatitis, dehydration, apathy, and anorexia · Animal treated and recovered after 4 months Second, captive bred · Kept together with other reptiles and a toad · Died after 2 weeks of anorexia · Other

  19. Failure of Viral Shells

    NASA Astrophysics Data System (ADS)

    Klug, William S.; Bruinsma, Robijn F.; Michel, Jean-Philippe; Knobler, Charles M.; Ivanovska, Irena L.; Schmidt, Christoph F.; Wuite, Gijs J. L.

    2006-12-01

    We report a combined theoretical and experimental study of the structural failure of viral shells under mechanical stress. We find that discontinuities in the force-indentation curve associated with failure should appear when the so-called Föppl von Kármán (FvK) number exceeds a critical value. A nanoindentation study of a viral shell subject to a soft-mode instability, where the stiffness of the shell decreases with increasing pH, confirms the predicted onset of failure as a function of the FvK number.

  20. Rare and emerging viral infections in transplant recipients.

    PubMed

    Waggoner, Jesse J; Soda, Elizabeth A; Deresinski, Stan

    2013-10-01

    Emerging viral pathogens include newly discovered viruses as well as previously known viruses that are either increasing, or threatening to increase in incidence. While often first identified in the general population, they may affect transplant recipients, in whom their manifestations may be atypical or more severe. Enhanced molecular methods have increased the rate of viral discovery but have not overcome the problem of demonstrating pathogenicity. At the same time, improved clinical diagnostic methods have increased the detection of reemerging viruses in immunocompromised patients. In this review, we first discuss viral diagnostics and the developing field of viral discovery and then focus on rare and emerging viruses in the transplant population: human T-cell leukemia virus type 1; hepatitis E virus; bocavirus; KI and WU polyomaviruses; coronaviruses HKU1 and NL63; influenza, H1N1; measles; dengue; rabies; and lymphocytic choriomeningitis virus. Detection and reporting of such rare pathogens in transplant recipients is critical to patient care and improving our understanding of posttransplant infections. PMID:23839998

  1. Modulation of pathogen recognition by autophagy.

    PubMed

    Oh, Ji Eun; Lee, Heung Kyu

    2012-01-01

    Autophagy is an ancient biological process for maintaining cellular homeostasis by degradation of long-lived cytosolic proteins and organelles. Recent studies demonstrated that autophagy is availed by immune cells to regulate innate immunity. On the one hand, cells exert direct effector function by degrading intracellular pathogens; on the other hand, autophagy modulates pathogen recognition and downstream signaling for innate immune responses. Pathogen recognition via pattern recognition receptors induces autophagy. The function of phagocytic cells is enhanced by recruitment of autophagy-related proteins. Moreover, autophagy acts as a delivery system for viral replication complexes to migrate to the endosomal compartments where virus sensing occurs. In another case, key molecules of the autophagic pathway have been found to negatively regulate immune signaling, thus preventing aberrant activation of cytokine production and consequent immune responses. In this review, we focus on the recent advances in the role of autophagy in pathogen recognition and modulation of innate immune responses. PMID:22566926

  2. Avian Diagnostic and Therapeutic Antibodies to Viral Emerging Pathogens

    SciTech Connect

    David Bradley

    2011-03-31

    During the current period the following key objectives were achieved: demonstration of high titer antibody production by geese following immunization with inactived H1N1 virus; completion of the epitope mapping of West Nile Virus-specific goose antibodies and initiation of epitope mapping of H1N1 flu-specific goose antibodies; advancement in scalable purification of goose antibodies.

  3. Discovery of a viral pathogen in the Asian citrus psyllid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We used a Metagenomics approach and discovered an insect-infecting virus in adult Asian citrus psyllids in Florida. Though wide spread in nature, this is the first report of a Fijivirus in North America. The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae) is a small insect tha...

  4. Richness and Composition of Niche-Assembled Viral Pathogen Communities

    E-print Network

    distributions to particular environmental conditions, hosts, or vectors. Here, we present results from *, Elizabeth T. Borer1 , Christelle Lacroix1 , Charles E. Mitchell2 , Alison G. Power3 1 Department of Ecology, Evolution, and Behavior, University of Minnesota, St. Paul, Minnesota, United States of America, 2

  5. Polypyrrole nanoribbon based chemiresistive immunosensors for viral plant pathogen detection

    E-print Network

    Chen, Wilfred

    including cucumbers, tomatoes, grapes, peanuts, tobaccos, etc.1 Due to its high transmission rate across-consuming processes. Therefore, the development of rapid, accurate, reliable, and miniaturized eld-deployable devices

  6. Viral surveillance and subclinical viral infection in pediatric kidney transplantation.

    PubMed

    Smith, Jodi M; Dharnidharka, Vikas R

    2015-05-01

    The more potent immunosuppressive therapy that has successfully reduced the incidence of acute rejection and improved graft outcomes has also resulted in a higher incidence of viral complications. Sensitive molecular methods now allow for the detection of subclinical viral infection, which is increasingly recognized due to the adoption of routine post-transplant viral surveillance protocols. The goal of viral surveillance is the detection of subclinical viral infection that triggers an intervention; one that either prevents progression to viral disease or leads to early diagnosis of viral disease, which is associated with improved outcomes. Knowledge of the epidemiology and natural history of subclinical viral infection and viral disease, as well as patient-specific risk factors, is required to establish the optimal surveillance schedule which achieves the goal of early diagnosis. Evidence that detection of subclinical viral infection can impact viral disease is variable depending on the virus. This review will summarize the current data on the role of viral surveillance for BK virus (BKV), cytomegalovirus (CMV), and the Epstein-Barr virus (EBV) in the pediatric kidney transplant population. PMID:25125226

  7. Viral Space Situational Awareness

    NASA Astrophysics Data System (ADS)

    Gleckler, A.; Butterfield, M. C.

    2012-09-01

    Viral SSA takes advantage of the amateur astronomy community to provide an extremely low-cost and geographically-diverse network of optical SSA sites. In the spirit of programs such as DARPA's Grand Challenge and the National Weather Service's program of providing amateur meteorologists with weather stations linked to a central professional meteorological facility, we form a cooperative bond with a willing community of technically-minded individuals. We term this program "viral" because we will qualify an initial set of astronomers for SSA operation and then use word of mouth in the astronomy community, as well as an outreach program, to pull in new observers. The use of modern remote controlled telescopes allows the incorporation of certified amateur, university, and commercial telescope systems. The availability of the local Viral SSA member for troubleshooting eliminates most significant costs of operating a large network. In this talk, we discuss the key concepts of Viral SSA and the route to a network of 100+ sites in a three year or less timeframe.

  8. Viral myelitis: an update.

    PubMed

    Kincaid, Octavia; Lipton, Howard L

    2006-11-01

    Viral infections of the central nervous system are uncommon but are important in the differential diagnosis of acute myelopathy. Acute viral myelitis can present as acute flaccid paralysis (poliomyelitis) or neurologic dysfunction due to involvement of the white matter. The latter usually affects only part of the transverse expanse of the spinal cord and manifests as asymmetric motor and sensory symptoms. When both halves of the spinal cord are affected, the entity is referred to as acute transverse myelitis and patients exhibit uniformly symmetric weakness, sensory loss, and urinary bladder involvement. Acute flaccid paralysis is due to cytolytic infection of anterior horn cells. When the involvement is mainly white matter, virus-specific and autoimmune host cellular immune responses are believed to contribute to spinal cord damage. Acute flaccid paralysis is caused by polioviruses-1, -2, and -3; coxsackieviruses A and B; enterovirus-71; and flaviviruses, including West Nile virus. Involvement of spinal cord white matter may be associated with infection by many different viruses; however, in most cases a specific viral cause is never determined. Chronic myelitis may be due to either direct infection of the spinal cord by human T-cell lymphotrophic virus-1 (HTLV-1), or a metabolic disturbance due to HIV-1 infection in AIDS patients; no other human virus is known to chronically infect the spinal cord without involvement of the brain. The principal treatment is antiviral drugs immediately upon virus isolation or the identification of a viral sequence by PCR and, when indicated, high doses of methylprednisolone. PMID:17074281

  9. Molecular Determinants of Enterovirus 71 Viral Entry

    PubMed Central

    Chen, Pan; Song, Zilin; Qi, Yonghe; Feng, Xiaofeng; Xu, Naiqing; Sun, Yinyan; Wu, Xing; Yao, Xin; Mao, Qunyin; Li, Xiuling; Dong, Wenjuan; Wan, Xiaobo; Huang, Niu; Shen, Xinliang; Liang, Zhenglun; Li, Wenhui

    2012-01-01

    Enterovirus 71 (EV71) is one of the major pathogens that cause hand, foot, and mouth disease outbreaks in young children in the Asia-Pacific region in recent years. Human scavenger receptor class B 2 (SCARB2) is the main cellular receptor for EV71 on target cells. The requirements of the EV71-SCARB2 interaction have not been fully characterized, and it has not been determined whether SCARB2 serves as an uncoating receptor for EV71. Here we compared the efficiency of the receptor from different species including human, horseshoe bat, mouse, and hamster and demonstrated that the residues between 144 and 151 are critical for SCARB2 binding to viral capsid protein VP1 of EV71 and seven residues from the human receptor could convert murine SCARB2, an otherwise inefficient receptor, to an efficient receptor for EV71 viral infection. We also identified that EV71 binds to SCARB2 via a canyon of VP1 around residue Gln-172. Soluble SCARB2 could convert the EV71 virions from 160 S to 135 S particles, indicating that SCARB2 is an uncoating receptor of the virus. The uncoating efficiency of SCARB2 significantly increased in an acidic environment (pH 5.6). These studies elucidated the viral capsid and receptor determinants of enterovirus 71 infection and revealed a possible target for antiviral interventions. PMID:22219187

  10. [Obesity development associated with viral infections].

    PubMed

    Jaworowska, Agnieszka; Bazylak, Grzegorz

    2006-01-01

    This overview of the significance of viral infections in the development of human obesity is presented within context of the commonly recognized obesity risk factors, including the personal and public health consequences of obesity in various countries. In addition, the results of past and recently published studies on the recognition of six taxonomically different viruses which can undoubtedly be associated with obesity progression in some species of animals are summarized. More attention is focused on the results of preliminary epidemiological studies indicating that human infection by the avian adenovirus SMAM-1 or the human adenovirus Ad-36 can be objectively related to symptoms, prevalence, and complications of obesity in some adult men. Proposed pathogenic pathways involved in the observed cases of viral infection-dependent obesity in animals and humans are also briefly described. Urgent implementation of high-throughput diagnostics procedures is advised to extend viral infection-oriented modes of prevention, recognition, and therapy of obesity currently available in modern societies. PMID:16641892

  11. Infectious pathogens and hematologic malignancy.

    PubMed

    Sadrzadeh, Hossein; Abtahi, Seyed M; Fathi, Amir T

    2012-12-01

    Infectious pathogens have been linked to the genesis of malignancy in a variety of different settings. Initial studies in virology led to the important discovery of key genetic alterations underlying common malignancies, and further, lent support to the notion that malignancy can be promoted by the process of viral infection and cellular transformation. In this review, we summarize a series of hematologic malignancies with derivations from and associations with infectious organisms. Among these are a variety of lymphomas, including Hodgkin's lymphoma (Hodgkin's disease), Burkitt lymphoma, and a host of other non-Hodgkin's lymphomas. Through innovative and ground-breaking studies, some of these malignancies have been directly linked to viral infection, such as the Epstein-Barr virus (EBV), while others have been merely associated with infection through epidemiologic studies and case-reports. Some malignancies have been demonstrated to be caused by viral infection, such as adult T-cell leukemia and lymphoma (ATLL), which is caused by the human T cell lymphotropic virus type I (HTLV-I), in certain endemic area. In the future, additional malignant states may be found to be associated with infectious etiology, which could allow for novel approaches to prevention and treatment. PMID:23272694

  12. Pathogenicity of fowl adenovirus in specific pathogen free chicken embryos.

    PubMed

    Alemnesh, W; Hair-Bejo, M; Aini, I; Omar, A R

    2012-01-01

    Inclusion body hepatitis (IBH) associated with fowl adenovirus (FAdV) infection has a worldwide distribution. The aim of the present study was to determine the pathogenicity of Malaysian FAdV serotype 9 (UPM04217) in specific pathogen free (SPF) embryonated chicken embryos. FAdV (titre 10(5.8)/ml) was inoculated into SPF embryonated chicken eggs (0.1 ml per egg) via the chorioallantoic membrane (CAM). There was 100% embryo mortality within 4-11 days post infection (dpi). The gross and microscopical lesions of the embryo were confined to the liver and were noted at 5, 7, 9 and 11 dpi. The liver was pale with multifocal areas of necrosis, fibrosis and haemorrhage. Microscopically, there was moderate to severe congestion and haemorrhage and severe and diffuse hepatocyte degeneration and necrosis, with intranuclear inclusion bodies (INIBs) and associated inflammation. Haemorrhage, congestion, degeneration, necrosis and hyperplasia of the CAM with INIBs were observed at 5, 7, 9 and 11 dpi. Varying degrees of congestion, haemorrhage, degeneration and necrosis were also observed in the yolk sac, kidney, spleen, heart and bursa of Fabricius. Ultrastructurally, numerous viral particles in the nucleus of hepatocytes were recorded at 7, 9 and 11 dpi, whereas at 5 dpi, fine granular and filamentous INIBs were observed. The INIBs in the CAM were present either as fine granular filamentous structures or as large viral inclusions. FAdV (UPM04217) is therefore highly pathogenic to SPF chicken embryos and the embryonic liver should be used for isolation and propagation of the virus. PMID:21705014

  13. Anti-viral instruction of bone marrow leukocytes during respiratory viral infections

    PubMed Central

    Hermesh, Tamar; Moltedo, Bruno; Moran, Thomas M.; López, Carolina B.

    2010-01-01

    Summary Respiratory viral infections are the cause of severe diseases in humans. The outcome of the infection depends on the interaction of the pathogen with the immune system. The bone marrow is the primary site of hematopoiesis and releases large numbers of leukocytes in response to inflammation. Here we show that during infection with influenza or Sendai virus the lung communicates with the sterile bone marrow through type I interferons. While in the bone marrow, leukocytes exposed to type I interferons activate an anti-viral transcriptional program and become resistant to infection with different viruses. The protected bone marrow leukocytes are capable of migrating to the infected lung and contribute to virus clearance. These findings show that appropriate instruction of cells during their development in the bone marrow is needed for the effective innate control of infection. PMID:20478536

  14. Authentic and Chimeric Full-Length Genomic cDNA Clones of Bovine Viral Diarrhea Virus That Yield Infectious Transcripts

    Microsoft Academic Search

    VENTZISLAV B. VASSILEV; MARC S. COLLETT; ANDRUBEN O. DONIS

    1997-01-01

    Bovine viral diarrhea virus (BVDV) is the most insidious and devastating viral pathogen of cattle in the United States. Disease control approaches must be based on detailed knowledge of virus biology. To develop reverse-genetic systems to study the molecular biology of the virus, wefirst constructed a plasmid containing the entire genome of BVDV cloned as cDNA. Subsequently, we showed that

  15. Detection of viral sequences in semen of honeybees ( Apis mellifera): Evidence for vertical transmission of viruses through drones

    Microsoft Academic Search

    Constanze Yue; Marion Schröder; Kaspar Bienefeld; Elke Genersch

    2006-01-01

    Honeybees (Apis mellifera) can be attacked by many eukaryotic parasites, and bacterial as well as viral pathogens. Especially in combination with the ectoparasitic mite Varroa destructor, viral honeybee diseases are becoming a major problem in apiculture, causing economic losses worldwide. Several horizontal transmission routes are described for some honeybee viruses. Here, we report for the first time the detection of

  16. Penicillium marneffei-Stimulated Dendritic Cells Enhance HIV-1 Trans-Infection and Promote Viral Infection by

    E-print Network

    Paris-Sud XI, Université de

    Penicillium marneffei-Stimulated Dendritic Cells Enhance HIV-1 Trans-Infection and Promote Viral Abstract Penicillium marneffei (P. marneffei) is considered an indicator pathogen of AIDS) Penicillium marneffei-Stimulated Dendritic Cells Enhance HIV-1 Trans-Infection and Promote Viral Infection

  17. Involvement of the PI3K and ERK signaling pathways in largemouth bass virus-induced apoptosis and viral replication.

    PubMed

    Huang, Xiaohong; Wang, Wei; Huang, Youhua; Xu, Liwen; Qin, Qiwei

    2014-12-01

    Increased reports demonstrated that largemouth Bass, Micropterus salmoides in natural and artificial environments were always suffered from an emerging iridovirus disease, largemouth Bass virus (LMBV). However, the underlying mechanism of LMBV pathogenesis remained largely unknown. Here, we investigated the cell signaling events involved in virus induced cell death and viral replication in vitro. We found that LMBV infection in epithelioma papulosum cyprini (EPC) cells induced typical apoptosis, evidenced by the appearance of apoptotic bodies, cytochrome c release, mitochondrial membrane permeabilization (MMP) destruction and reactive oxygen species (ROS) generation. Two initiators of apoptosis, caspase-8 and caspase-9, and the executioner of apoptosis, caspase-3, were all significantly activated with the infection time, suggested that not only mitochondrion-mediated, but also death receptor-mediated apoptosis were involved in LMBV infection. Reporter gene assay showed that the promoter activity of transcription factors including p53, NF-?B, AP-1 and cAMP response element-binding protein (CREB) were decreased during LMBV infection. After treatment with different signaling pathway inhibitors, virus production were significantly suppressed by the inhibition of phosphatidylinositol 3-kinase (PI3K) pathway and extracellular-signal-regulated kinases (ERK) signaling pathway. Furthermore, LMBV infection induced apoptosis was enhanced by PI3K inhibitor LY294002, but decreased by addition of ERK inhibitor UO126. Therefore, we speculated that apoptosis was sophisticatedly regulated by a series of cell signaling events for efficient virus propagation. Taken together, our results provided new insights into the molecular mechanism of ranavirus infection. PMID:25260912

  18. Viral Membrane Scission

    PubMed Central

    Rossman, Jeremy S.; Lamb, Robert A.

    2014-01-01

    Virus budding is a complex, multistep process in which viral proteins make specific alterations in membrane curvature. Many different viral proteins can deform the membrane and form a budding virion, but very few can mediate membrane scission to complete the budding process. As a result, enveloped viruses have developed numerous ways of facilitating membrane scission, including hijacking host cellular scission machinery and expressing their own scission proteins. These proteins mediate scission in very different ways, though the biophysical mechanics underlying their actions may be similar. In this review, we explore the mechanisms of membrane scission and the ways in which enveloped viruses use these systems to mediate the release of budding virions. PMID:24099087

  19. Viral haemorrhagic fever.

    PubMed

    Fhogartaigh, Caoimhe Nic; Aarons, Emma

    2015-02-01

    Viral haemorrhagic fevers (VHF) are a range of viral infections with potential to cause life-threatening illness in humans. Apart from Crimean-Congo haemorrhagic fever (CCHF), they are largely confined to Africa, distribution being dependent on the ecology of reservoir hosts. At present, the largest ever epidemic of Ebola virus disease (EVD or Ebola) is occurring in West Africa, raising the possibility that cases could be imported into non-endemic countries. Diagnosis and management is challenging due to the non-specificity of early symptoms, limited laboratory facilities in endemic areas, severity of disease, lack of effective therapy, strict infection control requirements and propensity to cause epidemics with secondary cases in healthcare workers. PMID:25650201

  20. Viral entry mechanisms: the increasing diversity of paramyxovirus entry

    PubMed Central

    Smith, Everett Clinton; Popa, Andreea; Chang, Andres; Masante, Cyril; Dutch, Rebecca Ellis

    2009-01-01

    The paramyxovirus family contains established human pathogens such as measles virus and human respiratory syncytial virus, and emerging pathogens including the Hendra and Nipah viruses and the recently identified human metapneumovirus. Two major envelope glycoproteins, the attachment protein and the fusion protein, promote the processes of viral attachment and virus-cell membrane fusion required for entry. While common mechanisms of fusion protein proteolytic activation and the mechanism of membrane fusion promotion have been shown in recent years, considerable diversity exists in the family related to receptor binding and the potential mechanisms of fusion triggering. PMID:19878307

  1. Current Approaches on Viral Infection: Proteomics and Functional Validations

    PubMed Central

    Zheng, Jie; Tan, Boon Huan; Sugrue, Richard; Tang, Kai

    2012-01-01

    Viruses could manipulate cellular machinery to ensure their continuous survival and thus become parasites of living organisms. Delineation of sophisticated host responses upon virus infection is a challenging task. It lies in identifying the repertoire of host factors actively involved in the viral infectious cycle and characterizing host responses qualitatively and quantitatively during viral pathogenesis. Mass spectrometry based proteomics could be used to efficiently study pathogen-host interactions and virus-hijacked cellular signaling pathways. Moreover, direct host and viral responses upon infection could be further investigated by activity-based functional validation studies. These approaches involve drug inhibition of secretory pathway, immunofluorescence staining, dominant negative mutant of protein target, real-time PCR, small interfering siRNA-mediated knockdown, and molecular cloning studies. In this way, functional validation could gain novel insights into the high-content proteomic dataset in an unbiased and comprehensive way. PMID:23162545

  2. Antiviral defense in shrimp: from innate immunity to viral infection.

    PubMed

    Wang, Pei-Hui; Huang, Tianzhi; Zhang, Xiaobo; He, Jian-Guo

    2014-08-01

    The culture of penaeid shrimp is rapidly developing as a major business endeavor worldwide. However, viral diseases have caused huge economic loss in penaeid shrimp culture industries. Knowledge of shrimp innate immunity and antiviral responses has made important progress in recent years, allowing the design of better strategies for the prevention and control of shrimp diseases. In this study, we have updated information on shrimp antiviral immunity and interactions between shrimp hosts and viral pathogens. Current knowledge and recent progress in immune signaling pathways (e.g., Toll/IMD-NF-?B and JAK-STAT signaling pathways), RNAi, phagocytosis, and apoptosis in shrimp antiviral immunity are discussed. The mechanism of viral infection in shrimp hosts and the interactions between viruses and shrimp innate immune systems are also analyzed. PMID:24886688

  3. Animal migration and risk of spread of viral infections: Chapter 9

    USGS Publications Warehouse

    Prosser, Diann J.; Nagel, Jessica; Takekawa, John Y.

    2013-01-01

    The potential contribution of migration towards the spread of disease is as varied as the ecology of the pathogens themselves and their host populations. This chapter outlines multiple examples of viral diseases in animal populations and their mechanisms of viral spread. Many species of insects, mammals, fish, and birds exhibit migratory behavior and have the potential to disperse diseases over long distances. The majority of studies available on viral zoonoses have focused on birds and bats, due to their highly migratory life histories. A number of studies have reported evidence of changes in the timing of animal migrations in response to climate change. The majority indicate an advancement of spring migration, with few or inconclusive results for fall migration. Predicting the combined effects of climate change on migratory patterns of host species and epidemiology of viral pathogens is complex and not fully realistic.

  4. Cellular immune therapy for viral infections in transplant patients

    PubMed Central

    Khanna, Rajiv; Smith, Corey

    2013-01-01

    Stem cell and organ transplantation are considered as the major advances of modern medicine. Unfortunately the success of transplantation is limited by its toxicity and infectious complications as a result of profound immunosuppression. Viral infections are an extremely common and predictable problem in these patients. Antiviral drugs given either prophylactically or as early therapy for patients with detectable viral loads appear to be an effective strategy for reducing viral infections. However, long-term treatment with these drugs is associated with significant toxicity, expense and the appearance of drug resistant virus isolates ultimately resulting in treatment failure. Over the last few years, there is increasing evidence that cellular immune therapies can reverse the outgrowth of haematological malignancies and can also provide therapeutic benefit against lethal viral infections. While the expansion and adoptive transfer of virus-specific T-cells from the healthy donor can be an effective strategy to control viral replication, this is not possible when donors are seronegative or are subsequently inaccessible. Recent studies have demonstrated successful expansion of virus-specific T-cells from seropositive stem cell transplant recipients of a seronegative graft with active virus disease and the long term reconstitution of protective anti-viral immunity following their adoptive transfer back into the patients. Furthermore, this immunotherapeutic strategy has also been extended for multiple pathogens including cytomegalovirus, Epstein-Barr virus, adenovirus and BK polyoma-virus. This approach can be employed to rapidly expand multiple pathogens-specific T cells that can be used for adoptive immunotherapy. Finally, new assays to monitor T cell immunity have been developed which will allow to identify the high risk transplant patients who may develop virus-associated complications post-transplantation and can be given adoptive T cell therapy prophylactically. PMID:24434332

  5. Host and viral ecology determine bat rabies seasonality and maintenance

    USGS Publications Warehouse

    George, D.B.; Webb, C.T.; Farnsworth, Matthew L.; O'Shea, T.J.; Bowen, R.A.; Smith, D.L.; Stanley, T.R.; Ellison, L.E.; Rupprecht, C.E.

    2011-01-01

    Rabies is an acute viral infection that is typically fatal. Most rabies modeling has focused on disease dynamics and control within terrestrial mammals (e.g., raccoons and foxes). As such, rabies in bats has been largely neglected until recently. Because bats have been implicated as natural reservoirs for several emerging zoonotic viruses, including SARS-like corona viruses, henipaviruses, and lyssaviruses, understanding how pathogens are maintained within a population becomes vital. Unfortunately, little is known about maintenance mechanisms for any pathogen in bat populations. We present a mathematical model parameterized with unique data from an extensive study of rabies in a Colorado population of big brown bats (Eptesicus fuscus) to elucidate general maintenance mechanisms. We propose that life history patterns of many species of temperate-zone bats, coupled with sufficiently long incubation periods, allows for rabies virus maintenance. Seasonal variability in bat mortality rates, specifically low mortality during hibernation, allows long-term bat population viability. Within viable bat populations, sufficiently long incubation periods allow enough infected individuals to enter hibernation and survive until the following year, and hence avoid an epizootic fadeout of rabies virus. We hypothesize that the slowing effects of hibernation on metabolic and viral activity maintains infected individuals and their pathogens until susceptibles from the annual birth pulse become infected and continue the cycle. This research provides a context to explore similar host ecology and viral dynamics that may explain seasonal patterns and maintenance of other bat-borne diseases.

  6. Genetic change in the open reading frame of bovine viral diarrhea virus is introduced more rapidly during the establishment of a single persistent infection than from multiple acute infections

    Microsoft Academic Search

    John D. Neill; Benjamin W. Newcomer; Shonda D. Marley; Julia F. Ridpath; M. Daniel Givens

    2011-01-01

    Bovine viral diarrhea viruses (BVDV) are ubiquitous viral pathogens of cattle with a high degree of sequence diversity amongst strains circulating in livestock herds. The driving force behind change in sequence is not well established but the inaccurate replication of the genomic RNA by a viral RNA polymerase without proof-reading capabilities as well as immune pressure on immunodominant proteins are

  7. Genetic change in the open reading frame of bovine viral diarrhea virus is introduced more rapidly during the establishment of a single persistent infection than by multiple acute infections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea viruses (BVDV) are ubiquitous viral pathogens of cattle. There is a high degree of sequence diversity between strains circulating in livestock herds. The driving force behind change in sequence is not known but the inaccurate replication of the genomic RNA by a viral RNA polyme...

  8. Bovine viral diarrhea: issues that need to be addressed as we work to improve BVDV control and move towards eradication

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acting alone or in conjunction with other pathogens, bovine viral diarrhea viruses (BVDV) are a source of major economic loss to the U.S. cattle producers. Losses are associated with outright mortality, reduced growth rates, reproductive failure and opportunistic infections by other pathogens in th...

  9. Viral surveillance and discovery

    PubMed Central

    Lipkin, Walter Ian; Firth, Cadhla

    2014-01-01

    The field of virus discovery has burgeoned with the advent of high throughput sequencing platforms and bioinformatics programs that enable rapid identification and molecular characterization of known and novel agents, investments in global microbial surveillance that include wildlife and domestic animals as well as humans, and recognition that viruses may be implicated in chronic as well as acute diseases. Here we review methods for viral surveillance and discovery, strategies and pitfalls in linking discoveries to disease, and identify opportunities for improvements in sequencing instrumentation and analysis, the use of social media and medical informatics that will further advance clinical medicine and public health. PMID:23602435

  10. Equine viral arteritis.

    PubMed

    Balasuriya, Udeni B R

    2014-12-01

    Equine arteritis virus (EAV), the causative agent of equine viral arteritis (EVA), is a respiratory and reproductive disease that occurs throughout the world. EAV infection is highly species-specific and exclusively limited to members of the family Equidae, which includes horses, donkeys, mules, and zebras. EVA is an economically important disease and outbreaks could cause significant losses to the equine industry. The primary objective of this article is to summarize current understanding of EVA, specifically the disease, pathogenesis, epidemiology, host immune response, vaccination and treatment strategies, prevention and control measures, and future directions. PMID:25441113

  11. Human viral gastroenteritis.

    PubMed Central

    Christensen, M L

    1989-01-01

    During the last 15 years, several different groups of fastidious viruses that are responsible for a large proportion of acute viral gastroenteritis cases have been discovered by the electron microscopic examination of stool specimens. This disease is one of the most prevalent and serious clinical syndromes seen around the world, especially in children. Rotaviruses, in the family Reoviridae, and fastidious fecal adenoviruses account for much of the viral gastroenteritis in infants and young children, whereas the small caliciviruses and unclassified astroviruses, and possibly enteric coronaviruses, are responsible for significantly fewer cases overall. In addition to electron microscopy, enzyme immunoassays and other rapid antigen detection systems have been developed to detect rotaviruses and fastidious fecal adenoviruses in the stool specimens of both nonhospitalized patients and those hospitalized for dehydration and electrolyte imbalance. Experimental rotavirus vaccines have also been developed, due to the prevalence and seriousness of rotavirus infection. The small, unclassified Norwalk virus and morphologically similar viruses are responsible for large and small outbreaks of acute gastroenteritis in older children, adolescents, and adults. Hospitalization of older patients infected with these viruses is usually not required, and their laboratory diagnoses have been limited primarily to research laboratories. Images PMID:2644024

  12. Characterization of an Antigenic Determinant of the Glycoprotein That Correlates with Pathogenicity of Rabies Virus

    Microsoft Academic Search

    Bernhard Dietzschold; William H. Wunner; Tadeusz J. Wiktor; A. Dwight Lopes; Monique Lafon; Carolyn L. Smith; Hilary Koprowski

    1983-01-01

    The pathogenicity of fixed rabies virus strains for adult mice depends on the presence of an antigenic determinant on the viral glycoprotein. Two virus-neutralizing monoclonal antibodies have been used to identify this determinant. All pathogenic strains of fixed rabies virus bind to these antibodies and are neutralized by them, whereas nonpathogenic strains fail to react with these monoclonal antibodies and

  13. DESCRIPTION AND ANALYSIS OF TWO INTERNET-BASED DATABASES OF INSECT PATHOGENS: EDWIP AND VIDIL

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 1996, two searchable databases covering insect pathogens were posted on the World Wide Web: the Ecological Database of the World's Insect Pathogens (EDWIP) and the Viral Diseases of Insects in the Literature database (VIDIL). In this paper, we describe the format and contents of EDWIP and VIDIL ...

  14. Molecular approaches to detecting and discriminating among prions, a class of pathogenic molecules(Abstract)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prions (PrPSc)are the pathogens that cause a set of fatal neurological diseases that include scrapie and chronic wasting disease (CWD). They are composed solely of protein and unlike viral, bacterial, or fungal pathogens, the information necessary to convert the normal cellular prion protein (PrPC) ...

  15. Viral diseases of the respiratory system.

    PubMed

    Villegas, P

    1998-08-01

    Infectious bronchitis, Newcastle disease, infectious laryngotracheitis, avian influenza, and pneumovirus are the viruses that more frequently affect the respiratory tract of chickens. Because of the tendency to change its antigenic properties, infectious bronchitis is currently the viral disease present in most poultry producing areas of the world. New serotypes and variant strains are reported in several countries. Current commercially available vaccines do not always provide protection against new field isolates. Vaccination programs are constantly adjusted in an attempt to improve protection against this disease. Infectious laryngotracheitis has appeared in the broiler industry as a serious disease. Improved vaccines are needed to control the disease in broilers. In the U.S., the control of the highly pathogenic forms of avian influenza and the velogenic forms of Newcastle disease have been achieved by eradication. In other countries, effective vaccines have been used to control Newcastle and avian influenza. Avian pneumovirus infection is also an emerging disease of chickens and turkeys. PMID:9706079

  16. A Strategy To Estimate Unknown Viral Diversity in Mammals

    PubMed Central

    Anthony, Simon J.; Epstein, Jonathan H.; Murray, Kris A.; Navarrete-Macias, Isamara; Zambrana-Torrelio, Carlos M.; Solovyov, Alexander; Ojeda-Flores, Rafael; Arrigo, Nicole C.; Islam, Ariful; Ali Khan, Shahneaz; Hosseini, Parviez; Bogich, Tiffany L.; Olival, Kevin J.; Sanchez-Leon, Maria D.; Karesh, William B.; Goldstein, Tracey; Luby, Stephen P.; Morse, Stephen S.; Mazet, Jonna A. K.; Daszak, Peter; Lipkin, W. Ian

    2013-01-01

    ABSTRACT The majority of emerging zoonoses originate in wildlife, and many are caused by viruses. However, there are no rigorous estimates of total viral diversity (here termed “virodiversity”) for any wildlife species, despite the utility of this to future surveillance and control of emerging zoonoses. In this case study, we repeatedly sampled a mammalian wildlife host known to harbor emerging zoonotic pathogens (the Indian Flying Fox, Pteropus giganteus) and used PCR with degenerate viral family-level primers to discover and analyze the occurrence patterns of 55 viruses from nine viral families. We then adapted statistical techniques used to estimate biodiversity in vertebrates and plants and estimated the total viral richness of these nine families in P. giganteus to be 58 viruses. Our analyses demonstrate proof-of-concept of a strategy for estimating viral richness and provide the first statistically supported estimate of the number of undiscovered viruses in a mammalian host. We used a simple extrapolation to estimate that there are a minimum of 320,000 mammalian viruses awaiting discovery within these nine families, assuming all species harbor a similar number of viruses, with minimal turnover between host species. We estimate the cost of discovering these viruses to be ~$6.3 billion (or ~$1.4 billion for 85% of the total diversity), which if annualized over a 10-year study time frame would represent a small fraction of the cost of many pandemic zoonoses. PMID:24003179

  17. Autologous Antibody Capture to Enrich Immunogenic Viruses for Viral Discovery

    PubMed Central

    Deijs, Martin; Jonkers, Jiri; Verhoeven, Joost T. P.; Ieven, Margareta; Goossens, Herman; de Jong, Menno D.; Berkhout, Ben; Loens, Katherine; Kellam, Paul; Bakker, Margreet; Canuti, Marta; Cotten, Matthew; van der Hoek, Lia

    2013-01-01

    Discovery of new viruses has been boosted by novel deep sequencing technologies. Currently, many viruses can be identified by sequencing without knowledge of the pathogenicity of the virus. However, attributing the presence of a virus in patient material to a disease in the patient can be a challenge. One approach to meet this challenge is identification of viral sequences based on enrichment by autologous patient antibody capture. This method facilitates identification of viruses that have provoked an immune response within the patient and may increase the sensitivity of the current virus discovery techniques. To demonstrate the utility of this method, virus discovery deep sequencing (VIDISCA-454) was performed on clinical samples from 19 patients: 13 with a known respiratory viral infection and 6 with a known gastrointestinal viral infection. Patient sera was collected from one to several months after the acute infection phase. Input and antibody capture material was sequenced and enrichment was assessed. In 18 of the 19 patients, viral reads from immunogenic viruses were enriched by antibody capture (ranging between 1.5x to 343x in respiratory material, and 1.4x to 53x in stool). Enriched reads were also determined in an identity independent manner by using a novel algorithm Xcompare. In 16 of the 19 patients, 21% to 100% of the enriched reads were derived from infecting viruses. In conclusion, the technique provides a novel approach to specifically identify immunogenic viral sequences among the bulk of sequences which are usually encountered during virus discovery metagenomics. PMID:24223808

  18. Architecture and regulation of negative-strand viral enzymatic machinery

    PubMed Central

    Kranzusch, Philip J.; Whelan, Sean P.J.

    2012-01-01

    Negative-strand (NS) RNA viruses initiate infection with a unique polymerase complex that mediates both mRNA transcription and subsequent genomic RNA replication. For nearly all NS RNA viruses, distinct enzymatic domains catalyzing RNA polymerization and multiple steps of 5? mRNA cap formation are contained within a single large polymerase protein (L). While NS RNA viruses include a variety of emerging human and agricultural pathogens, the enzymatic machinery driving viral replication and gene expression remains poorly understood. Recent insights with Machupo virus and vesicular stomatitis virus have provided the first structural information of viral L proteins, and revealed how the various enzymatic domains are arranged into a conserved architecture shared by both segmented and nonsegmented NS RNA viruses. In vitro systems reconstituting RNA synthesis from purified components provide new tools to understand the viral replicative machinery, and demonstrate the arenavirus matrix protein regulates RNA synthesis by locking a polymerase–template complex. Inhibition of gene expression by the viral matrix protein is a distinctive feature also shared with influenza A virus and nonsegmented NS RNA viruses, possibly illuminating a conserved mechanism for coordination of viral transcription and polymerase packaging PMID:22767259

  19. STAT2 deficiency and susceptibility to viral illness in humans

    PubMed Central

    Hambleton, Sophie; Goodbourn, Stephen; Young, Dan F.; Dickinson, Paul; Mohamad, Siti M. B.; Valappil, Manoj; McGovern, Naomi; Cant, Andrew J.; Hackett, Scott J.; Ghazal, Peter; Morgan, Neil V.; Randall, Richard E.

    2013-01-01

    Severe infectious disease in children may be a manifestation of primary immunodeficiency. These genetic disorders represent important experiments of nature with the capacity to elucidate nonredundant mechanisms of human immunity. We hypothesized that a primary defect of innate antiviral immunity was responsible for unusually severe viral illness in two siblings; the proband developed disseminated vaccine strain measles following routine immunization, whereas an infant brother died after a 2-d febrile illness from an unknown viral infection. Patient fibroblasts were indeed abnormally permissive for viral replication in vitro, associated with profound failure of type I IFN signaling and absence of STAT2 protein. Sequencing of genomic DNA and RNA revealed a homozygous mutation in intron 4 of STAT2 that prevented correct splicing in patient cells. Subsequently, other family members were identified with the same genetic lesion. Despite documented infection by known viral pathogens, some of which have been more severe than normal, surviving STAT2-deficient individuals have remained generally healthy, with no obvious defects in their adaptive immunity or developmental abnormalities. These findings imply that type I IFN signaling [through interferon-stimulated gene factor 3 (ISGF3)] is surprisingly not essential for host defense against the majority of common childhood viral infections. PMID:23391734

  20. 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

  1. Detection of viral hemorrhagic septicemia virus

    USGS Publications Warehouse

    Winton, James; Kurath, Gael; Batts, William

    2007-01-01

    Viral hemorrhagic septicemia virus (VHSV) is considered to be one of the most important viral pathogens of finfish and is listed as reportable by many nations and international organizations (Office International des Epizooties 2006). Prior to 1988, VHSV was thought to be limited to Europe (Wolf 1988; Smail 1999). Subsequently, it was shown that the virus is endemic among many marine and anadromous fish species in both the Pacific and Atlantic Oceans (Meyers and Winton 1995; Skall et al. 2005). Genetic analysis reveals that isolates of VHSV can be divided into four genotypes that generally correlate with geographic location with the North American isolates generally falling into VHSV Genotype IV (Snow et al. 2004). In 2005-2006, reports from the Great Lakes region indicated that wild fish had experienced disease or, in some cases, very large die-offs from VHSV (Elsayed et al. 2006, Lumsden et al. 2007). The new strain from the Great Lakes, now identified as VHSV Genotype IVb, appears most closely related to isolates of VHSV from mortalities that occurred during 2000-2004 in rivers and near-shore areas of New Brunswick and Nova Scotia, Canada (Gagne et al. 2007). The type IVb isolate found in the Great Lakes region is the only strain outside of Europe that has been associated with significant mortality in freshwater species.

  2. Nonlytic viral spread enhanced by autophagy components

    PubMed Central

    Bird, Sara Whitney; Maynard, Nathaniel D.; Covert, Markus W.; Kirkegaard, Karla

    2014-01-01

    The cell-to-cell spread of cytoplasmic constituents such as nonenveloped viruses and aggregated proteins is usually thought to require cell lysis. However, mechanisms of unconventional secretion have been described that bypass the secretory pathway for the extracellular delivery of cytoplasmic molecules. Components of the autophagy pathway, an intracellular recycling process, have been shown to play a role in the unconventional secretion of cytoplasmic signaling proteins. Poliovirus is a lytic virus, although a few examples of apparently nonlytic spread have been documented. Real demonstration of nonlytic spread for poliovirus or any other cytoplasmic constituent thought to exit cells via unconventional secretion requires demonstration that a small amount of cell lysis in the cellular population is not responsible for the release of cytosolic material. Here, we use quantitative time-lapse microscopy to show the spread of infectious cytoplasmic material between cells in the absence of lysis. siRNA-mediated depletion of autophagy protein LC3 reduced nonlytic intercellular viral transfer. Conversely, pharmacological stimulation of the autophagy pathway caused more rapid viral spread in tissue culture and greater pathogenicity in mice. Thus, the unconventional secretion of infectious material in the absence of cell lysis is enabled by components of the autophagy pathway. It is likely that other nonenveloped viruses also use this pathway for nonlytic intercellular spread to affect pathogenesis in infected hosts. PMID:25157142

  3. An atomistic approach to viral mechanical oscillations

    NASA Astrophysics Data System (ADS)

    Sankey, Otto F.

    2009-03-01

    Viruses are the simplest ``life'' form. These parasites reproduce by borrowing the machinery of their host cell. Many are pathogenic to plants, animals, and humans. Viruses possess an outer protein coat (capsid) that protects its genomic material that resides inside. We have developed a theoretical technique to model the very low frequency mechanical modes of the viral capsid with atomic resolution. The method uses empirical force fields and a mathematical framework borrowed from electronic structure theory for finding low energy states. The low frequency modes can be ``pinged'' with an ultra-short laser pulse and the aim of the light/vibrational coupling is to interfere with the viral life cycle. The theoretical work here is motivated by the recent work of Tsen et al. [2] who have used ultra-short pulsed laser scattering to inactivate viruses. The methodology can be applied to many systems, and the coupled mechanical oscillations of other floppy biomolecules such as a complete ATP binding cassette (ABC transporter) will also be discussed. Co-authors of this work are Dr. Eric Dykeman, Prof. K.-T. Tsen and Daryn Benson. [4pt] [1] E.C. Dykeman et al., Phys. Rev. Lett., 100, 028101 (2008). [0pt] [2] K-T. Tsen et al., J. of Physics -- Cond. Mat. 19, 472201 (2007).

  4. Viral hepatitis in India.

    PubMed

    Acharya, S K; Madan, Kaushal; Dattagupta, S; Panda, S K

    2006-01-01

    Viral hepatitis is a major public health problem in India, which is hyperendemic for HAV and HEV. Seroprevalence studies reveal that 90%-100% of the population acquires anti-HAV antibody and becomes immune by adolescence. Many epidemics of HEV have been reported from India. HAV related liver disease is uncommon in India and occurs mainly in children. HEV is also the major cause of sporadic adult acute viral hepatitis and ALF. Pregnant women and patients with CLD constitute the high risk groups to contract HEV infection, and HEV-induced mortality among them is substantial, which underlines the need for preventive measures for such groups. Children with HAV and HEV coinfection are prone to develop ALF. India has intermediate HBV endemicity, with a carrier frequency of 2%-4%. HBV is the major cause of CLD and HCC. Chronic HBV infection in India is acquired in childhood, presumably before 5 years of age, through horizontal transmission. Vertical transmission of HBV in India is considered to be infrequent. Inclusion of HBV vaccination in the expanded programme of immunization is essential to reduce the HBV carrier frequency and disease burden. HBV genotypes A and D are prevalent in India, which are similar to the HBV genotypes in the West. HCV infection in India has a population prevalence of around 1%, and occurs predominantly through transfusion and the use of unsterile glass syringes. HCV genotypes 3 and 2 are prevalent in 60%-80% of the population and they respond well to a combination of interferon and ribavirin. About 10%-15% of CLD and HCC are associated with HCV infection in India. HCV infection is also a major cause of post-transfusion hepatitis. HDV infection is infrequent in India and is present about 5%-10% of patients with HBV-related liver disease. HCC appears to be less common in India than would be expected from the prevalence rates of HBV and HCV. The high disease burden of viral hepatitis and related CLD in India, calls for the setting up of a hepatitis registry and formulation of government-supported prevention and control strategies. PMID:17100109

  5. New developments in viral peptides and APL induction.

    PubMed

    Gharavi, A E; Pierangeli, S S; Harris, E N

    2000-09-01

    The associations of antiphospholipid antibodies (aPL) with thrombosis and fetal death are well recognized, but the mechanism(s) that induce their production are not. We demonstrated induction of pathogenic aPL antibodies by immunization with foreign beta(2)-GPI, or synthetic peptides representing the PL-binding site of the beta(2)-GPI. These antibodies caused intrauterine fetal death and transverse myelopathy due to spinal cord infarction in mice, and activated endothelial cells in vitro. We also introduced aPL in mice by immunization with PL-binding viral peptides and observed their pathogenic effects. This study demonstrated that pathogenic effects of aPL antibodies induced by immunization with a human CMV-derived PL-binding synthetic peptide. We hypothesize that in APS patients aPL is induced by beta(2)-GPL-like PL-binding products of human common bacteria or viruses. PMID:10968915

  6. Evolution of a Simian Immunodeficiency Virus Pathogen

    PubMed Central

    Edmonson, Paul; Murphey-Corb, Michael; Martin, Louis N.; Delahunty, Claire; Heeney, Jonathan; Kornfeld, Hardy; Donahue, Peter R.; Learn, Gerald H.; Hood, Leroy; Mullins, James I.

    1998-01-01

    Analysis of disease induction by simian immunodeficiency viruses (SIV) in macaques was initially hampered by a lack of molecularly defined pathogenic strains. The first molecularly cloned SIV strains inoculated into macaques, SIVmacBK28 and SIVmacBK44 (hereafter designated BK28 and BK44, respectively), were cases in point, since they failed to induce disease within 1 year postinoculation in any inoculated animal. Here we report the natural history of infection with BK28 and BK44 in inoculated rhesus macaques and efforts to increase the pathogenicity of BK28 through genetic manipulation and in vivo passage. BK44 infection resulted in no disease in four animals infected for more than 7 years, whereas BK28 induced disease in less than half of animals monitored for up to 7 years. Elongation of the BK28 transmembrane protein (TM) coding sequence truncated by prior passage in human cells marginally increased pathogenicity, with two of four animals dying in the third year and one dying in the seventh year of infection. Modification of the BK28 long terminal repeat to include four consensus nuclear factor SP1 and two consensus NF-?B binding sites enhanced early virus replication without augmenting pathogenicity. In contrast, in vivo passage of BK28 from the first animal to die from immunodeficiency disease (1.5 years after infection) resulted in a consistently pathogenic strain and a 50% survival time of about 1.3 years, thus corresponding to one of the most pathogenic SIV strains identified to date. To determine whether the diverse viral quasispecies that evolved during in vivo passage was required for pathogenicity or whether a more virulent virus variant had evolved, we generated a molecular clone composed of the 3? half of the viral genome derived from the in vivo-passaged virus (H824) fused with the 5? half of the BK28 genome. Kinetics of disease induction with this cloned virus (BK28/H824) were similar to those with the in vivo-passaged virus, with four of five animals surviving less than 1.7 years. Thus, evolution of variants with enhanced pathogenicity can account for the increased pathogenicity of this SIV strain. The genetic changes responsible for this virulent transformation included at most 59 point mutations and 3 length-change mutations. The critical mutations were likely to have been multiple and dispersed, including elongation of the TM and Nef coding sequences; changes in RNA splice donor and acceptor sites, TATA box sites, and Sp1 sites; multiple changes in the V2 region of SU, including a consensus neutralization epitope; and five new N-linked glycosylation sites in SU. PMID:9420239

  7. Dengue viral infections

    PubMed Central

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing this disease. Early recognition and prompt initiation of appropriate treatment are vital if disease related morbidity and mortality are to be limited. This review outlines aspects of the epidemiology of dengue infections, the dengue virus and its mosquito vector, clinical features and pathogenesis of dengue infections, and the management and control of these infections. PMID:15466994

  8. Pathogens Hijack the Epigenome

    PubMed Central

    Silmon de Monerri, Natalie C.; Kim, Kami

    2015-01-01

    Pathogens have evolved strategies to promote their survival by dramatically modifying the transcriptional profile and protein content of the host cells they infect. Modifications of the host transcriptome and proteome are mediated by pathogen-encoded effector molecules that modulate host cells through a variety of different mechanisms. Recent studies highlight the importance of the host chromatin and other epigenetic regulators as targets of pathogens. Host gene regulatory mechanisms may be targeted through cytoplasmic signaling, directly by pathogen effector proteins, and possibly by pathogen RNA. Although many of these changes are short-lived and persist only during the course of infection, several studies indicate that pathogens are able to induce long-term, heritable changes that are essential to pathogenesis of infectious diseases and persistence of pathogens within their hosts. In this review, we discuss how pathogens modulate the epigenome of host cells, a new and flourishing avenue of host-pathogen interaction studies. PMID:24525150

  9. Production methods for viral particles.

    PubMed

    Machida, Kodai; Imataka, Hiroaki

    2015-04-01

    Viral particles and virus-like particles (VLPs) or capsids are becoming important vehicles and templates in bio-imaging, drug delivery and materials sciences. Viral particles are prepared by infecting the host organism but VLPs are obtained from cells that express a capsid protein. Some VLPs are disassembled and then re-assembled to incorporate a material of interest. Cell-free systems, which are amenable to manipulating the viral assembly process, are also available for producing viral particles. Regardless of the production system employed, the particles are functionalized by genetic and/or chemical engineering. Here, we review various methods for producing and functionalizing viral particles and VLPs, and we discuss the merits of each system. PMID:25488519

  10. New global viral threats.

    PubMed

    Erdem, Hakan; Ünal, Serhat

    2015-04-01

    Infectious diseases have caused great catastrophes in human history, as in the example of the plague, which wiped out half of the population in Europe in the 14th century. Ebola virus and H7N9 avian influenza virus are 2 lethal pathogens that we have encountered in the second decade of the 21st century. Ebola infection is currently being seen in West Africa, and H7N9 avian flu appears to have settled in Southeast Asia. This article focuses on the current situation and the future prospects of these potential infectious threats to mankind. PMID:25828274

  11. Correlations between Microbial Indicators, Pathogens, and Environmental Factors in a Subtropical Estuary

    PubMed Central

    Ortega, Cristina; Solo-Gabriele, Helena M.; Abdelzaher, Amir; Wright, Mary; Deng, Yang; Stark, Lillian M.

    2009-01-01

    The objective of this study was to evaluate whether indicator microbes and physical-chemical parameters were correlated with pathogens within a tidally influenced estuary. Measurements included the analysis of physical-chemical parameters (pH, salinity, temperature, and turbidity), measurements of bacterial indicators (enterococci, fecal coliform, E. coli, and total coliform), viral indicators (somatic and MS2 coliphage), viral pathogens (enterovirus by culture), and protozoan pathogens (Cryptosporidium and Giardia). All pathogen results were negative with the exception of one sample which tested positive for culturable reovirus (8.5 MPN/100 L).. Notable physical-chemical parameters for this sample included low salinity (<1 ppt) and high water temperature (31 °C). Indicator bacteria and indicator virus levels for this sample were within average values typically measured within the study site and were low in comparison with levels observed in other freshwater environments. Overall results suggest that high levels of bacterial and viral indicators were associated with low salinity sites. PMID:19464704

  12. RAB11-mediated trafficking in host-pathogen interactions.

    PubMed

    Guichard, Annabel; Nizet, Victor; Bier, Ethan

    2014-09-01

    Many bacterial and viral pathogens block or subvert host cellular processes to promote successful infection. One host protein that is targeted by invading pathogens is the small GTPase RAB11, which functions in vesicular trafficking. RAB11 functions in conjunction with a protein complex known as the exocyst to mediate terminal steps in cargo transport via the recycling endosome to cell-cell junctions, phagosomes and cellular protrusions. These processes contribute to host innate immunity by promoting epithelial and endothelial barrier integrity, sensing and immobilizing pathogens and repairing pathogen-induced cellular damage. In this Review, we discuss the various mechanisms that pathogens have evolved to disrupt or subvert RAB11-dependent pathways as part of their infection strategy. PMID:25118884

  13. Enteric pathogens through life stages

    PubMed Central

    Kolling, Glynis; Wu, Martin; Guerrant, Richard L.

    2012-01-01

    Enteric infections and diarrheal diseases constitute pervasive health burdens throughout the world, with rates being highest at the two ends of life. During the first 2–3 years of life, much of the disease burden may be attributed to infection with enteric pathogens including Salmonella, rotavirus, and many other bacterial, viral, and protozoan organisms; however, infections due to Clostridium difficile exhibit steady increases with age. Still others, like Campylobacter infections in industrialized settings are high in early life (<2 years old) and increase again in early adulthood (called the “second weaning” by some). The reasons for these differences undoubtedly reside in part in pathogen differences; however, host factors including the commensal intestinal microbial communities, immune responses (innate and acquired), and age-dependant shifts likely play important roles. Interplay of these factors is illustrated by studies examining changes in human gut microbiota with inflammatory bowel disease and irritable bowel syndrome. Recent gut microbial surveys have indicated dramatic shifts in gut microbial population structure from infants to young adults to the elders. An understanding of the evolution of these factors and their interactions (e.g., how does gut microbiota modulate the “inflamm-aging” process or vice versa) through the human life “cycle” will be important in better addressing and controlling these enteric infections and their consequences for both quality and quantity of life (often assessed as disability adjusted life-years or “DALYs”). PMID:22937528

  14. PATHOGENS: VIEWS OF EPA'S PATHOGEN EQUIVALENCY COMMITTEE

    EPA Science Inventory

    This presentation reviews the pathogenic microorganisms that may be found in municipal sewage sludge and the commonly employed Class A and B processes for controlling pathogens. It notes how extensively they are used and discusses issues and concerns with their application. Pre...

  15. Host genetic determinants of influenza pathogenicity

    PubMed Central

    Lin, Tsai-Yu; Brass, Abraham L.

    2014-01-01

    Despite effective vaccines, influenza remains a major global health threat due to the morbidity and mortality caused by seasonal epidemics, as well as the 2009 pandemic. Also of profound concern are the rare but potentially catastrophic transmissions of avian influenza to humans, highlighted by a recent H7N9 influenza outbreak. Murine and human studies reveal that the clinical course of influenza is the result of a combination of both host and viral genetic determinants. While viral pathogenicity has long been the subject of intensive efforts, research to elucidate host genetic determinants, particularly human, is now in the ascendant, and the goal of this review is to highlight these recent insights. PMID:23933004

  16. Fine mapping of loci on BTA2 and BTA26 associated with bovine viral diarrhea persistent infection and linked with bovine respiratory disease in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine respiratory disease (BRD) is considered to be the most costly infectious disease in the cattle industry. Bovine viral diarrhea virus (BVDV) is one of the pathogens involved with the BRD complex of disease. Bovine viral diarrhea virus infection also negatively impacts cow reproduction and calf...

  17. BTA2 and BTA26 are linked with bovine respiratory disease and associated with persistent infection of bovine viral diarrhea virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus is a pathogen associated with bovine respiratory disease (BRD). BRD causes 28% of all cattle deaths and an annual U.S. loss over $692 million. The objective of this study was to refine the linkage of BRD and association of bovine viral diarrhea-persistent infection (BVD-P...

  18. Molecular basis of host specificity in human pathogenic bacteria

    PubMed Central

    Pan, Xiaolei; Yang, Yang; Zhang, Jing-Ren

    2014-01-01

    Pathogenic bacteria display various levels of host specificity or tropism. While many bacteria can infect a wide range of hosts, certain bacteria have strict host selectivity for humans as obligate human pathogens. Understanding the genetic and molecular basis of host specificity in pathogenic bacteria is important for understanding pathogenic mechanisms, developing better animal models and designing new strategies and therapeutics for the control of microbial diseases. The molecular mechanisms of bacterial host specificity are much less understood than those of viral pathogens, in part due to the complexity of the molecular composition and cellular structure of bacterial cells. However, important progress has been made in identifying and characterizing molecular determinants of bacterial host specificity in the last two decades. It is now clear that the host specificity of bacterial pathogens is determined by multiple molecular interactions between the pathogens and their hosts. Furthermore, certain basic principles regarding the host specificity of bacterial pathogens have emerged from the existing literature. This review focuses on selected human pathogenic bacteria and our current understanding of their host specificity.

  19. Viral infections in pregnancy.

    PubMed

    Haun, L; Kwan, N; Hollier, L M

    2007-04-01

    Viral infections are a common complication of pregnancy and in some cases, can have profound effects for the unborn fetus. The human herpesvirus family is composed of large, enveloped DNA viruses that have close structural similarity. The family includes the herpes simplex viruses types 1 and 2, varicella zoster virus, Epstein Barr virus, cytomegalovirus (CMV), and human herpes viruses types 6, 7 and 8. These viruses all share the ability to establish latency and reactivate at a later time. Structural fetal abnormalities can result from intrauterine infection and transmission of the infection during the pregnancy or at the time of delivery can result in important neonatal disease. Human parvovirus B19 is a DNA virus with strong tropism for erythroid precursors and infection during pregnancy can result in fetal hydrops and stillbirth. The causative agents of hepatitis are hepatotropic viruses termed hepatitis A, B, C, D (deltavirus) and E. All except hepatitis B virus are RNA viruses. Vertical transmission of maternal infection with hepatitis B and C can result in significant long term sequelae. PMID:17505458

  20. Cellular Visualization of Macrophage Pyroptosis and Interleukin-1? Release in a Viral Hemorrhagic Infection in Zebrafish Larvae

    PubMed Central

    Varela, Mónica; Romero, Alejandro; Dios, Sonia; van der Vaart, Michiel; Figueras, Antonio; Meijer, Annemarie H.

    2014-01-01

    ABSTRACT Hemorrhagic viral diseases are distributed worldwide with important pathogens, such as dengue virus or hantaviruses. The lack of adequate in vivo infection models has limited the research on viral pathogenesis and the current understanding of the underlying infection mechanisms. Although hemorrhages have been associated with the infection of endothelial cells, other cellular types could be the main targets for hemorrhagic viruses. Our objective was to take advantage of the use of zebrafish larvae in the study of viral hemorrhagic diseases, focusing on the interaction between viruses and host cells. Cellular processes, such as transendothelial migration of leukocytes, virus-induced pyroptosis of macrophages. and interleukin-1? (Il-1?) release, could be observed in individual cells, providing a deeper knowledge of the immune mechanisms implicated in the disease. Furthermore, the application of these techniques to other pathogens will improve the current knowledge of host-pathogen interactions and increase the potential for the discovery of new therapeutic targets. IMPORTANCE Pathogenic mechanisms of hemorrhagic viruses are diverse, and most of the research regarding interactions between viruses and host cells has been performed in cell lines that might not be major targets during natural infections. Thus, viral pathogenesis research has been limited because of the lack of adequate in vivo infection models. The understanding of the relative pathogenic roles of the viral agent and the host response to the infection is crucial. This will be facilitated by the establishment of in vivo infection models using organisms such as zebrafish, which allows the study of the diseases in the context of a complete individual. The use of this animal model with other pathogens could improve the current knowledge on host-pathogen interactions and increase the potential for the discovery of new therapeutic targets against diverse viral diseases. PMID:25100833

  1. Noncytopathic Bovine Viral Diarrhea Virus Inhibits Double-Stranded RNA-Induced Apoptosis and Interferon Synthesis

    Microsoft Academic Search

    MATTHIAS SCHWEIZER; ERNST PETERHANS

    2001-01-01

    Bovine viral diarrhea virus (BVDV), a pestivirus of the Flaviviridae family, is an economically important cattle pathogen with a worldwide distribution. Both noncytopathic (ncp) and cytopathic (cp) biotypes of BVDV can be isolated from persistently infected cattle suffering from the lethal mucosal disease. The cp biotype correlates with the production of the NS3 nonstructural protein, which in the corresponding ncp

  2. CD46 Is a Cellular Receptor for Bovine Viral Diarrhea Virus

    Microsoft Academic Search

    Karin Maurer; Thomas Krey; Volker Moennig; Heinz-Jurgen Thiel; Till Rumenapf

    2004-01-01

    Bovine viral diarrhea virus (BVDV) is a small enveloped RNA virus which belongs to the genus Pestivirus within the family Flaviviridae. Pestiviruses are widespread among cloven- hoofed animals (Artiodactyla), causing disease in ruminants (Bos, Ovis, and Camelidae) and nonruminants (Suidae). BVDV is an important pathogen of cattle and accounts for syndromes of the intestinal, respiratory, and reproductive tracts. While the

  3. VIRAL RESCUE FROM AN INFECTIOUS CLONE OF A MESOGENIC NEWCASTLE DISEASE VIRUS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reverse genetics is a powerful tool for the study of viral pathogenesis of negative stranded RNA viruses through the manipulation of genes associated with interactions of the pathogen with the host. The present work describes the generation of an infectious clone of the Newcastle disease virus Anhin...

  4. Viral, Bacterial and Parasitic Etiology of Pediatric Diarrhea in Gaza, Palestine

    Microsoft Academic Search

    Farid H. Abu-Elamreen; Abdalla A. Abed; Fadel A. Sharif

    2008-01-01

    Objectives: To determine the etiology of acute diarrhea in Palestinian children under 5 years of age and to improve knowledge of the etiology of gastrointestinal pathogens using traditional and molecular diagnostic techniques. Materials and Methods: Various common enteropathogens (viral, bacterial and parasites) associated with diarrhea were investigated by conventional and molecular techniques (PCR) in 150 children less than 5 years

  5. Discovery and initial analysis of novel viral genomes in the soybean cyst nematode

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nematodes are the most abundant multi-cellular animals on earth, yet little is known about their natural viral pathogens and no nematode virus genomes have been published. Consequently, nematode viruses have been overlooked as important biotic factors in the study of nematode ecology. Here we show t...

  6. Edinburgh Research Explorer Host Phylogeny Determines Viral Persistence and Replication in

    E-print Network

    Obbard, Darren

    Kingdom Abstract Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding diseaseEdinburgh Research Explorer Host Phylogeny Determines Viral Persistence and Replication in Novel

  7. Parvovirus B19 DNA CpG Dinucleotide Methylation and Epigenetic Regulation of Viral Expression

    PubMed Central

    Bonvicini, Francesca; Manaresi, Elisabetta; Di Furio, Francesca; De Falco, Luisa; Gallinella, Giorgio

    2012-01-01

    CpG DNA methylation is one of the main epigenetic modifications playing a role in the control of gene expression. For DNA viruses whose genome has the ability to integrate in the host genome or to maintain as a latent episome, a correlation has been found between the extent of DNA methylation and viral quiescence. No information is available for Parvovirus B19, a human pathogenic virus, which is capable of both lytic and persistent infections. Within Parvovirus B19 genome, the inverted terminal regions display all the characteristic signatures of a genomic CpG island; therefore we hypothesised a role of CpG dinucleotide methylation in the regulation of viral genome expression. The analysis of CpG dinucleotide methylation of Parvovirus B19 DNA was carried out by an aptly designed quantitative real-time PCR assay on bisulfite-modified DNA. The effects of CpG methylation on the regulation of viral genome expression were first investigated by transfection of either unmethylated or in vitro methylated viral DNA in a model cell line, showing that methylation of viral DNA was correlated to lower expression levels of the viral genome. Then, in the course of in vitro infections in different cellular environments, it was observed that absence of viral expression and genome replication were both correlated to increasing levels of CpG methylation of viral DNA. Finally, the presence of CpG methylation was documented in viral DNA present in bioptic samples, indicating the occurrence and a possible role of this epigenetic modification in the course of natural infections. The presence of an epigenetic level of regulation of viral genome expression, possibly correlated to the silencing of the viral genome and contributing to the maintenance of the virus in tissues, can be relevant to the balance and outcome of the different types of infection associated to Parvovirus B19. PMID:22413013

  8. Statistical Mechanics of Viral Entry

    NASA Astrophysics Data System (ADS)

    Zhang, Yaojun; Dudko, Olga K.

    2015-01-01

    Viruses that have lipid-membrane envelopes infect cells by fusing with the cell membrane to release viral genes. Membrane fusion is known to be hindered by high kinetic barriers associated with drastic structural rearrangements—yet viral infection, which occurs by fusion, proceeds on remarkably short time scales. Here, we present a quantitative framework that captures the principles behind the invasion strategy shared by all enveloped viruses. The key to this strategy—ligand-triggered conformational changes in the viral proteins that pull the membranes together—is treated as a set of concurrent, bias field-induced activated rate processes. The framework results in analytical solutions for experimentally measurable characteristics of virus-cell fusion and enables us to express the efficiency of the viral strategy in quantitative terms. The predictive value of the theory is validated through simulations and illustrated through recent experimental data on influenza virus infection.

  9. Aseptic Meningitis and Viral Myelitis

    PubMed Central

    Irani, David N.

    2008-01-01

    SYNOPSIS Meningitis and myelitis represent common and very infrequent viral infections of the central nervous system (CNS), respectively. Indeed, the number of cases of viral meningitis that occurs annually exceeds the total number of meningitis cases caused by all other etiologies combined. Focal CNS infections, on the other hand, such as occur in the spinal cord with viral myelitis, are much less common and may be confused with non-infectious disorders that cause acute flaccid paralysis (AFP). This chapter will review some of the important clinical features, epidemiology, diagnostic approaches, and management strategies for patients with aseptic meningitis and viral myelitis. Particular focus will be placed on the diseases caused by enteroviruses (EVs), which as a group account for the vast majority of all aseptic meningitis cases as well as many focal infections of the spinal cord. PMID:18657719

  10. Update on selected viral exanthems.

    PubMed

    Nelson, J S; Stone, M S

    2000-08-01

    Viral exanthems are common in childhood and account for a large number of patient visits to pediatric or family medicine clinics. Most exanthems are virtually harmless to the healthy child, but others can be signs of more significant systemic disease. Some exanthems that are benign or self-limited in the healthy child may propose significant risk to pregnant or immunocompromised individuals. Therefore, recognition of exanthems, which may be associated with certain viral illnesses, is important for the primary care provider. For example, prompt recognition of a viral exanthem caused by parvovirus may allow a pregnant female from exposing her fetus to a potentially fatal infection, or, if the exposure has already occurred, may indicate the need for appropriate fetal monitoring. In this manuscript, we review the recent literature pertaining to four characteristic exanthems that are thought to be viral in nature: papular purpuric gloves and socks syndrome; pityriasis rosea; unilateral lateral thoracic exanthem; and Gianotti-Crosti syndrome. PMID:10943817

  11. [Acute viral hepatitis during pregnancy].

    PubMed

    Valdés R, Enrique; Sepúlveda M, Alvaro; Candia P, Paula; Lattes A, Karina

    2010-12-01

    Acute hepatitis has a very low incidence disease during pregnancy. However, it may be an important cause of jaundice during gestation which in cases of viral etiology can have a very high morbidity and mortality risk to the mother and the fetus. The purpose of this review is to update the available knowledge regarding viral hepatitis during pregnancy including description of the main etiologies, transmission route, maternal-fetal risk and possible management. PMID:21279287

  12. Viral RNAs Are Unusually Compact

    PubMed Central

    Gopal, Ajaykumar; Egecioglu, Defne E.; Yoffe, Aron M.; Ben-Shaul, Avinoam; Rao, Ayala L. N.; Knobler, Charles M.; Gelbart, William M.

    2014-01-01

    A majority of viruses are composed of long single-stranded genomic RNA molecules encapsulated by protein shells with diameters of just a few tens of nanometers. We examine the extent to which these viral RNAs have evolved to be physically compact molecules to facilitate encapsulation. Measurements of equal-length viral, non-viral, coding and non-coding RNAs show viral RNAs to have among the smallest sizes in solution, i.e., the highest gel-electrophoretic mobilities and the smallest hydrodynamic radii. Using graph-theoretical analyses we demonstrate that their sizes correlate with the compactness of branching patterns in predicted secondary structure ensembles. The density of branching is determined by the number and relative positions of 3-helix junctions, and is highly sensitive to the presence of rare higher-order junctions with 4 or more helices. Compact branching arises from a preponderance of base pairing between nucleotides close to each other in the primary sequence. The density of branching represents a degree of freedom optimized by viral RNA genomes in response to the evolutionary pressure to be packaged reliably. Several families of viruses are analyzed to delineate the effects of capsid geometry, size and charge stabilization on the selective pressure for RNA compactness. Compact branching has important implications for RNA folding and viral assembly. PMID:25188030

  13. Hepcidin Induction by Pathogens and Pathogen-Derived Molecules Is Strongly Dependent on Interleukin-6

    PubMed Central

    Rodriguez, Richard; Jung, Chun-Ling; Gabayan, Victoria; Deng, Jane C.; Ganz, Tomas; Nemeth, Elizabeta

    2014-01-01

    Hepcidin, the iron-regulatory hormone, is increased during infection or inflammation, causing hypoferremia. This response is thought to be a host defense mechanism that restricts iron availability to invading pathogens. It is not known if hepcidin is differentially induced by bacterial versus viral infections, whether the stimulation of pattern recognition receptors directly regulates hepcidin transcription, or which of the proposed signaling pathways are essential for hepcidin increase during infection. We analyzed hepcidin induction and its dependence on interleukin-6 (IL-6) in response to common bacterial or viral infections in mice or in response to a panel of pathogen-derived molecules (PAMPs) in mice and human primary hepatocytes. In wild-type (WT) mice, hepcidin mRNA was induced several hundred-fold both by a bacterial (Streptococcus pneumoniae) and a viral infection (influenza virus PR8) within 2 to 5 days. Treatment of mice and human primary hepatocytes with most Toll-like receptor ligands increased hepcidin mRNA within 6 h. Hepcidin induction by microbial stimuli was IL-6 dependent. IL-6 knockout mice failed to increase hepcidin in response to S. pneumoniae or influenza infection and had greatly diminished hepcidin response to PAMPs. In vitro, hepcidin induction by PAMPs in primary human hepatocytes was abolished by the addition of neutralizing IL-6 antibodies. Our results support the key role of IL-6 in hepcidin regulation in response to a variety of infectious and inflammatory stimuli. PMID:24478088

  14. Papillomaviruses: Viral evolution, cancer and evolutionary medicine.

    PubMed

    Bravo, Ignacio G; Félez-Sánchez, Marta

    2015-01-01

    Papillomaviruses (PVs) are a numerous family of small dsDNA viruses infecting virtually all mammals. PVs cause infections without triggering a strong immune response, and natural infection provides only limited protection against reinfection. Most PVs are part and parcel of the skin microbiota. In some cases, infections by certain PVs take diverse clinical presentations from highly productive self-limited warts to invasive cancers. We propose PVs as an excellent model system to study the evolutionary interactions between the immune system and pathogens causing chronic infections: genotypically, PVs are very diverse, with hundreds of different genotypes infecting skin and mucosa; phenotypically, they display extremely broad gradients and trade-offs between key phenotypic traits, namely productivity, immunogenicity, prevalence, oncogenicity and clinical presentation. Public health interventions have been launched to decrease the burden of PV-associated cancers, including massive vaccination against the most oncogenic human PVs, as well as systematic screening for PV chronic anogenital infections. Anti-PVs vaccines elicit protection against infection, induce cross-protection against closely related viruses and result in herd immunity. However, our knowledge on the ecological and intrapatient dynamics of PV infections remains fragmentary. We still need to understand how the novel anthropogenic selection pressures posed by vaccination and screening will affect viral circulation and epidemiology. We present here an overview of PV evolution and the connection between PV genotypes and the phenotypic, clinical manifestations of the diseases they cause. This differential link between viral evolution and the gradient cancer-warts-asymptomatic infections makes PVs a privileged playground for evolutionary medicine research. PMID:25634317

  15. Emerging Pathogens – How Safe is Blood?

    PubMed Central

    Schmidt, Michael; Geilenkeuser, Wolf-Jochen; Sireis, Walid; Seifried, Erhard; Hourfar, Kai

    2014-01-01

    Summary During the last few decades, blood safety efforts were mainly focused on preventing viral infections. However, humanity's increased mobility and improved migration pathways necessitate a global perspective regarding other transfusion-transmitted pathogens. This review focuses on the general infection risk of blood components for malaria, dengue virus, Trypanosoma cruzi (Chagas disease) and Babesia spp. Approximately 250 million people become infected by Plasmodium spp. per year. Dengue virus affects more than 50 million people annually in more than 100 countries; clinically, it can cause serious diseases, such as dengue haemorrhagic fever and dengue shock syndrome. Chagas disease, which is caused by Trypanosoma cruzi, mainly occurs in South America and infects approximately 10 million people annually. Babesia spp. is a parasitic infection that infects red blood cells; although many infections are asymptomatic, severe clinical disease has been reported, especially in the elderly. Screening assays are available for all considered pathogens but make screening strategies more complex and more expensive. A general pathogen inactivation for all blood components (whole blood) promises to be a long-term, sustainable solution for both known and unknown pathogens. Transfusion medicine therefore eagerly awaits such a system. PMID:24659943

  16. Recent insights into the evolution of innate viral sensing in animals

    PubMed Central

    Lewis, Samuel H; Obbard, Darren J

    2014-01-01

    The evolution of viral sensors is likely to be shaped by the constraint imposed through high conservation of viral Pathogen-Associated Molecular Patterns (PAMPs), and by the potential for ‘arms race’ coevolution with more rapidly evolving viral proteins. Here we review the recent progress made in understanding the evolutionary history of two types of viral sensor, RNA helicases and Toll-like receptors. We find differences both in their rates of evolution, and in the levels of positive selection they experience. We suggest that positive selection has been the primary driver of the rapid evolution of the RNA helicases, while selective constraint has been a stronger influence shaping the slow evolution of the Toll-like receptors. PMID:25042205

  17. Superinfection exclusion by Citrus tristeza virus does not correlate with the production of viral small RNAs.

    PubMed

    Folimonova, Svetlana Y; Harper, Scott J; Leonard, Michael T; Triplett, Eric W; Shilts, Turksen

    2014-11-01

    Superinfection exclusion (SIE), a phenomenon in which a preexisting viral infection prevents a secondary infection with the same or closely related virus, has been described for different viruses, including important pathogens of humans, animals, and plants. Several mechanisms acting at various stages of the viral life cycle have been proposed to explain SIE. Most cases of SIE in plant virus systems were attributed to induction of RNA silencing, a host defense mechanism that is mediated by small RNAs. Here we show that SIE by Citrus tristeza virus (CTV) does not correlate with the production of viral small interfering RNAs (siRNAs). CTV variants, which differed in the SIE ability, had similar siRNAs profiles. Along with our previous observations that the exclusion phenomenon requires a specific viral protein, p33, the new data suggest that SIE by CTV is highly complex and appears to use different mechanisms than those proposed for other viruses. PMID:25248160

  18. Viral evasion mechanisms of early antiviral responses involving regulation of ubiquitin pathways

    PubMed Central

    Rajsbaum, Ricardo; García-Sastre, Adolfo

    2013-01-01

    Early innate and cell-intrinsic responses are essential to protect host cells against pathogens. In turn, viruses have developed sophisticated mechanisms to establish productive infections, counteracting the host innate immune responses. Increasing evidence indicates that these antiviral factors may have a dual role by directly inhibiting viral replication, as well as by sensing and transmitting signals to induce antiviral cytokines. Recent studies have pointed at new, unappreciated mechanisms of viral evasion of host innate protective responses including manipulating the host ubiquitin system. Viral inhibition of antiviral factors by ubiquitin-dependent degradation is emerging as critical evasion mechanism of the antiviral response. In addition, recent studies have uncovered new mechanisms by which viral encoded proteins inhibit ubiquitin and ubiquitin-like modification of host proteins involved innate immune signaling pathways. Here we discuss recent findings and novel strategies that viruses have developed to counteract these early innate antiviral defenses. PMID:23850008

  19. Influence of host resistance on viral adaptation: hepatitis C virus as a case study

    PubMed Central

    Plauzolles, Anne; Lucas, Michaela; Gaudieri, Silvana

    2015-01-01

    Genetic and cellular studies have shown that the host’s innate and adaptive immune responses are an important correlate of viral infection outcome. The features of the host’s immune response (host resistance) reflect the coevolution between hosts and pathogens that has occurred over millennia, and that has also resulted in a number of strategies developed by viruses to improve fitness and survival within the host (viral adaptation). In this review, we discuss viral adaptation to host immune pressure via protein–protein interactions and sequence-specific mutations. Specifically, we will present the “state of play” on viral escape mutations to host T-cell responses in the context of the hepatitis C virus, and their influence on infection outcome.

  20. A Mutation in the Ebola Virus Envelope Glycoprotein Restricts Viral Entry in a Host Species-and Cell-Type-Specific Manner

    E-print Network

    Chandran, Kartik

    A Mutation in the Ebola Virus Envelope Glycoprotein Restricts Viral Entry in a Host Species, Bronx, New York, USAb Zaire Ebola virus (EBOV) is a zoonotic pathogen that causes severe hemorrhagic APCs. Zaire Ebola virus (EBOV) is an emerging zoonotic pathogen that causes hemorrhagic fever in humans

  1. Survey of Wastewater Indicators and Human Pathogen Genomes in Biosolids Produced by Class A and Class B Stabilization Treatments

    Microsoft Academic Search

    Emily Viau; Jordan Peccia

    2009-01-01

    Accurate modeling of the infectious aerosol risk associated with the land application of biosolids requires an in-depth knowledge of the magnitudes and changes in pathogen concentrations for a variety of class A and class B stabilization methods. The following survey used quantitative PCR (qPCR) and culture assays to detect environmentally resistant bacterial and viral pathogens and biosolid indicator organisms for

  2. Infection of United States swine with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To assess the pathogenic effects of Type 2 highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) on healthy 10-week old commercial swine in the United States, viral kinetics and resultant disease caused by intranasal inoculation of such virus rescued from an infectious clo...

  3. Human mast cell activation with viruses and pathogen products.

    PubMed

    Haidl, Ian D; Marshall, Jean S

    2015-01-01

    Mast cells have been demonstrated to have critical roles in host defense against a number of types of pathogens. In order to better understand how mast cells participate in effective immune responses, it is important to evaluate their ability to respond directly to pathogens and their products. In the current chapter we provide a methodology to evaluate human mast cell responses to a number of bacterial and fungal pathogen products and to mammalian reovirus as a model of acute viral infection. These methods should provide key information necessary to aid in the effective design of experiments to evaluate human mast cell responses to a number of other organisms. However, it is important to carefully consider the biology of the mast cell subsets and pathogens involved and the optimal experimental conditions necessary to evaluate mediators of interest. PMID:25388252

  4. Development of an aquatic pathogen database (AquaPathogen X) and its utilization in tracking emerging fish virus pathogens in North America

    USGS Publications Warehouse

    Emmenegger, E.J.; Kentop, E.; Thompson, T.M.; Pittam, S.; Ryan, A.; Keon, D.; Carlino, J.A.; Ranson, J.; Life, R.B.; Troyer, R.M.; Garver, K.A.; Kurath, G.

    2011-01-01

    The AquaPathogen X database is a template for recording information on individual isolates of aquatic pathogens and is freely available for download (http://wfrc.usgs.gov). This database can accommodate the nucleotide sequence data generated in molecular epidemiological studies along with the myriad of abiotic and biotic traits associated with isolates of various pathogens (e.g. viruses, parasites and bacteria) from multiple aquatic animal host species (e.g. fish, shellfish and shrimp). The cataloguing of isolates from different aquatic pathogens simultaneously is a unique feature to the AquaPathogen X database, which can be used in surveillance of emerging aquatic animal diseases and elucidation of key risk factors associated with pathogen incursions into new water systems. An application of the template database that stores the epidemiological profiles of fish virus isolates, called Fish ViroTrak, was also developed. Exported records for two aquatic rhabdovirus species emerging in North America were used in the implementation of two separate web-accessible databases: the Molecular Epidemiology of Aquatic Pathogens infectious haematopoietic necrosis virus (MEAP-IHNV) database (http://gis.nacse.org/ihnv/) released in 2006 and the MEAP- viral haemorrhagic septicaemia virus (http://gis.nacse.org/vhsv/) database released in 2010.

  5. Resequencing Pathogen Microarray (RPM) for prospective detection and identification of emergent pathogen strains and variants

    NASA Astrophysics Data System (ADS)

    Tibbetts, Clark; Lichanska, Agnieszka M.; Borsuk, Lisa A.; Weslowski, Brian; Morris, Leah M.; Lorence, Matthew C.; Schafer, Klaus O.; Campos, Joseph; Sene, Mohamadou; Myers, Christopher A.; Faix, Dennis; Blair, Patrick J.; Brown, Jason; Metzgar, David

    2010-04-01

    High-density resequencing microarrays support simultaneous detection and identification of multiple viral and bacterial pathogens. Because detection and identification using RPM is based upon multiple specimen-specific target pathogen gene sequences generated in the individual test, the test results enable both a differential diagnostic analysis and epidemiological tracking of detected pathogen strains and variants from one specimen to the next. The RPM assay enables detection and identification of pathogen sequences that share as little as 80% sequence similarity to prototype target gene sequences represented as detector tiles on the array. This capability enables the RPM to detect and identify previously unknown strains and variants of a detected pathogen, as in sentinel cases associated with an infectious disease outbreak. We illustrate this capability using assay results from testing influenza A virus vaccines configured with strains that were first defined years after the design of the RPM microarray. Results are also presented from RPM-Flu testing of three specimens independently confirmed to the positive for the 2009 Novel H1N1 outbreak strain of influenza virus.

  6. Reverse transcriptase directs viral evolution in a deep ocean methane seep

    NASA Astrophysics Data System (ADS)

    Paul, B. G.; Bagby, S. C.

    2013-12-01

    Deep ocean methane seeps are sites of intense microbial activity, with complex communities fueled by aerobic and anaerobic methanotrophy. Methane consumption in these communities has a substantial impact on the global carbon cycle, yet little is known about their evolutionary history or their likely evolutionary trajectories in a warming ocean. As in other marine systems, viral predation and virally mediated horizontal gene transfer are expected to be major drivers of evolutionary change in these communities; however, the host cells' resistance to cultivation has impeded direct study of the viral population. We conducted a metagenomic study of viruses in the anoxic sediments of a deep methane seep in the Santa Monica Basin in the Southern California Bight. We retrieved 1660 partial viral genomes, tentatively assigning 1232 to bacterial hosts and 428 to archaea. One abundant viral genome, likely hosted by Clostridia species present in the sediment, was found to encode a diversity-generating retroelement (DGR), a module for reverse transcriptase-mediated directed mutagenesis of a distal tail fiber protein. While DGRs have previously been described in the viruses of human pathogens, where diversification of viral tail fibers permits infection of a range of host cell types, to our knowledge this is the first description of such an element in a marine virus. By providing a mechanism for massively broadening potential host range, the presence of DGRs in these systems may have a major impact on the prevalence of virally mediated horizontal gene transfer, and even on the phylogenetic distances across which genes are moved.

  7. Pathogenic Microorganisms in Water

    NSDL National Science Digital Library

    Melissa Lenczewski

    Pathogenic Microorganisms in Water: Traditionally, groundwater has been used without treatment because the soil acts as a filter, removing pathogenic microorganisms. Some potential sources of pathogens (or disease causing organisms) in groundwater include septic tanks, leaking sewer lines, sewage sludge, intentional groundwater recharge with sewage, irrigation with sewage, direct injection of sewage, domestic solid waste disposal (landfills) and sewage oxidation ponds. The objective of the session is to introduce hydrogeologist to the types of microorganisms, sources of pathogens, and a simple exercise that can be incorporated into a hydrogeology class.

  8. Autophagy vitalizes the pathogenicity of pathogenic fungi.

    PubMed

    Liu, Xiao-Hong; Gao, Hui-Min; Xu, Fei; Lu, Jian-Ping; Devenish, Rodney J; Lin, Fu-Cheng

    2012-10-01

    Plant pathogenic fungi utilize a series of complex infection structures, in particular the appressorium, to gain entry to and colonize plant tissue. As a consequence of the accumulation of huge quantities of glycerol in the cell the appressorium generates immense intracellular turgor pressure allowing the penetration peg of the appressorium to penetrate the leaf cuticle. Autophagic processes are ubiquitous in eukaryotic cells and facilitate the bulk degradation of macromolecules and organelles. The study of autophagic processes has been extended from the model yeast Saccharomyces cerevisiae to pathogenic fungi such as the rice blast fungus Magnaporthe oryzae. Significantly, null mutants for the expression of M. oryzae autophagy gene homologs lose their pathogenicity for infection of host plants. Clarification of the functions and network of interactions between the proteins expressed by M. oryzae autophagy genes will lead to a better understanding of the role of autophagy in fungal pathogenesis and help in the development of new strategies for disease control. PMID:22935638

  9. Innate antiviral immune signaling, viral evasion and modulation by HIV-1.

    PubMed

    Rustagi, Arjun; Gale, Michael

    2014-03-20

    The intracellular innate antiviral response in human cells is an essential component of immunity against virus infection. As obligate intracellular parasites, all viruses must evade the actions of the host cell's innate immune response in order to replicate and persist. Innate immunity is induced when pathogen recognition receptors of the host cell sense viral products including nucleic acid as "non-self". This process induces downstream signaling through adaptor proteins to activate latent transcription factors that drive the expression of genes encoding antiviral and immune modulatory effector proteins that restrict virus replication and regulate adaptive immunity. The interferon regulatory factors (IRFs) are transcription factors that play major roles in innate immunity. In particular, IRF3 is activated in response to infection by a range of viruses including RNA viruses, DNA viruses and retroviruses. Among these viruses, human immunodeficiency virus type 1 (HIV-1) remains a major global health problem mediating chronic infection in millions of people wherein recent studies show that viral persistence is linked with the ability of the virus to dysregulate and evade the innate immune response. In this review, we discuss viral pathogen sensing, innate immune signaling pathways and effectors that respond to viral infection, the role of IRF3 in these processes and how it is regulated by pathogenic viruses. We present a contemporary overview of the interplay between HIV-1 and innate immunity, with a focus on understanding how innate immune control impacts infection outcome and disease. PMID:24326250

  10. Emerging foodborne pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The emergence of new foodborne pathogens is due to a number of factors. An important factor is the globalization of the food supply with the possibility of the introduction of foodborne pathogens from other countries. Animal husbandry, food production, food processing, and food distribution system...

  11. Highly Pathogenic Avian Influenza

    E-print Network

    Boyer, Edmond

    Highly Pathogenic Avian Influenza Virus (H5N1) Outbreak in Captive Wild Birds and Cats, Cambodia Tamao Wildlife Rescue Centre, Cambodia, was affected by the highly pathogenic influenza virus (H5N1). Birds from 26 species died. Influenza virus subtype H5N1 was detected in 6 of 7 species tested. Cats

  12. Emerging Escherichia Pathogen

    PubMed Central

    Permpalung, Nitipong; Sentochnik, Deborah E.

    2013-01-01

    Escherichia hermannii was first identified as a new species in 1982. It has rarely been reported as a human pathogen. We report the first case of E. hermannii as the sole pathogen in a catheter-related bloodstream infection. PMID:23740732

  13. Plant pathogen resistance

    DOEpatents

    Greenberg, Jean T; Jung, Ho Won; Tschaplinski, Timothy

    2012-11-27

    Azelaic acid or its derivatives or analogs induce a robust and a speedier defense response against pathogens in plants. Azelaic acid treatment alone does not induce many of the known defense-related genes but activates a plant's defense signaling upon pathogen exposure.

  14. BACTERIAL WATERBORNE PATHOGENS

    EPA Science Inventory

    Bacterial pathogens are examples of classical etiological agents of waterborne disease. While these agents no longer serve as major threats to U.S. water supplies, they are still important pathogens in areas with substandard sanitation and poor water treatment facilities. In th...

  15. Bacterial, Fungal, Parasitic, and Viral Myositis

    PubMed Central

    Crum-Cianflone, Nancy F.

    2008-01-01

    Infectious myositis may be caused by a broad range of bacterial, fungal, parasitic, and viral agents. Infectious myositis is overall uncommon given the relative resistance of the musculature to infection. For example, inciting events, including trauma, surgery, or the presence of foreign bodies or devitalized tissue, are often present in cases of bacterial myositis. Bacterial causes are categorized by clinical presentation, anatomic location, and causative organisms into the categories of pyomyositis, psoas abscess, Staphylococcus aureus myositis, group A streptococcal necrotizing myositis, group B streptococcal myositis, clostridial gas gangrene, and nonclostridial myositis. Fungal myositis is rare and usually occurs among immunocompromised hosts. Parasitic myositis is most commonly a result of trichinosis or cystericercosis, but other protozoa or helminths may be involved. A parasitic cause of myositis is suggested by the travel history and presence of eosinophilia. Viruses may cause diffuse muscle involvement with clinical manifestations, such as benign acute myositis (most commonly due to influenza virus), pleurodynia (coxsackievirus B), acute rhabdomyolysis, or an immune-mediated polymyositis. The diagnosis of myositis is suggested by the clinical picture and radiologic imaging, and the etiologic agent is confirmed by microbiologic or serologic testing. Therapy is based on the clinical presentation and the underlying pathogen. PMID:18625683

  16. Pathogens involved in lower respiratory tract infections in general practice.

    PubMed Central

    Graffelman, A Willy; Knuistingh Neven, Arie; le Cessie, Saskia; Kroes, Aloys C M; Springer, Machiel P; van den Broek, Peterhans J

    2004-01-01

    BACKGROUND: There are few investigations into the aetiology of lower respiratory tract infections (LRTIs) in general practice. AIM: To describe the aetiology of LRTI among adult patients in general practice in The Netherlands. DESIGN OF STUDY: Prospective observational study. SETTING: General practices in the Leiden region, The Netherlands. METHOD: Adult patients with a defined LRTI were included. Standard medical history and physical examination were performed. Sputum, blood and throat swabs were collected for diagnostic tests. Aetiological diagnosis, categorised as definite or possible, was based on the results of bacterial and viral cultures, serological techniques, and on polymerase chain reaction. Proportions of pathogens causing LRTI were assessed in relation to chest X-ray findings. RESULTS: A bacterial cause was established in 43 (30%), and a viral cause in 57 (39%) of the 145 patients with a LRTI. Influenza virus A was the most frequently diagnosed microorganism, followed by Haemophilus influenzae, and Mycoplasma pneumoniae. Streptococcus pneumoniae was found in 6% of the patients. CONCLUSIONS: Pathogens were found in two-thirds of the patients. In half of these patients there was a viral cause. Influenza virus A was the most frequently found pathogen. The treatment with antibiotics of at least one-third of the patients with LRTI was superfluous. This observation should result in changes in the prescription of antibiotics in LRTI. PMID:14965401

  17. Pathogenesis and transmissibility of highly (H7N1) and low (H7N9) pathogenic avian influenza virus infection in red-legged partridge (Alectoris rufa)

    Microsoft Academic Search

    Kateri Bertran; Elisa Pérez-Ramírez; Núria Busquets; Roser Dolz; Antonio Ramis; Ayub Darji; Francesc Xavier Abad; Rosa Valle; Aida Chaves; Júlia Vergara-Alert; Marta Barral; Ursula Höfle; Natàlia Majó

    2011-01-01

    An experimental infection with highly pathogenic avian influenza virus (HPAIV) and low pathogenic avian influenza virus (LPAIV) was carried out in red-legged partridges (Alectoris rufa) in order to study clinical signs, gross and microscopic lesions, and viral distribution in tissues and viral shedding. Birds were infected with a HPAIV subtype H7N1 (A\\/Chicken\\/Italy\\/5093\\/1999) and a LPAIV subtype H7N9 (A\\/Anas crecca\\/Spain\\/1460\\/2008). Uninoculated

  18. Nosocomial Spread of Viral Disease

    PubMed Central

    Aitken, Celia; Jeffries, Donald J.

    2001-01-01

    Viruses are important causes of nosocomial infection, but the fact that hospital outbreaks often result from introduction(s) from community-based epidemics, together with the need to initiate specific laboratory testing, means that there are usually insufficient data to allow the monitoring of trends in incidences. The most important defenses against nosocomial transmission of viruses are detailed and continuing education of staff and strict adherence to infection control policies. Protocols must be available to assist in the management of patients with suspected or confirmed viral infection in the health care setting. In this review, we present details on general measures to prevent the spread of viral infection in hospitals and other health care environments. These include principles of accommodation of infected patients and approaches to good hygiene and patient management. They provide detail on individual viral diseases accompanied in each case with specific information on control of the infection and, where appropriate, details of preventive and therapeutic measures. The important areas of nosocomial infection due to blood-borne viruses have been extensively reviewed previously and are summarized here briefly, with citation of selected review articles. Human prion diseases, which present management problems very different from those of viral infection, are not included. PMID:11432812

  19. The Paradigm of Viral Communication.

    ERIC Educational Resources Information Center

    Welker, Carl B.

    2002-01-01

    Introduces the concepts of idea viruses and viral communication, a technology-based communication that spreads ideas quickly. Explains its applicability in the area of direct marketing and discusses a technology platform that provides the opportunity of sending a message to a large number of people and emotional or pecuniary incentives to…

  20. VIRAL EVOLUTION Genomic surveillance elucidates

    E-print Network

    Napp, Nils

    VIRAL EVOLUTION Genomic surveillance elucidates Ebola virus origin and transmission during the 2014,12,13 § Robert F. Garry,8 § S. Humarr Khan,3 § Pardis C. Sabeti1,2 § In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78

  1. Applying horizontal gene transfer phenomena to enhance non-viral gene therapy

    PubMed Central

    Elmer, Jacob J.; Christensen, Matthew D.; Rege, Kaushal

    2014-01-01

    Horizontal gene transfer (HGT) is widespread amongst prokaryotes, but eukaryotes tend to be far less promiscuous with their genetic information. However, several examples of HGT from pathogens into eukaryotic cells have been discovered and mimicked to improve non-viral gene delivery techniques. For example, several viral proteins and DNA sequences have been used to significantly increase cytoplasmic and nuclear gene delivery. Plant genetic engineering is routinely performed with the pathogenic bacterium Agrobacterium tumefaciens and similar pathogens (e.g. Bartonella henselae) may also be able to transform human cells. Intracellular parasites like Trypanosoma cruzi may also provide new insights into overcoming cellular barriers to gene delivery. Finally, intercellular nucleic acid transfer between host cells will also be briefly discussed. This article will review the unique characteristics of several different viruses and microbes and discuss how their traits have been successfully applied to improve non-viral gene delivery techniques. Consequently, pathogenic traits that originally caused diseases may eventually be used to treat many genetic diseases. PMID:23994344

  2. Amino Acid Substitutions in PB1 of Avian Influenza Viruses Influence Pathogenicity and Transmissibility in Chickens

    PubMed Central

    Suzuki, Yasushi; Uchida, Yuko; Tanikawa, Taichiro; Maeda, Naohiro; Takemae, Nobuhiro

    2014-01-01

    ABSTRACT Amino acid substitutions were introduced into avian influenza virus PB1 in order to characterize the interaction between polymerase activity and pathogenicity. Previously, we used recombinant viruses containing the hemagglutinin (HA) and neuraminidase (NA) genes from the highly pathogenic avian influenza virus (HPAIV) H5N1 strain and other internal genes from two low-pathogenicity avian influenza viruses isolated from chicken and wild-bird hosts (LP and WB, respectively) to demonstrate that the pathogenicity of highly pathogenic avian influenza viruses (HPAIVs) of subtype H5N1 in chickens is regulated by the PB1 gene (Y. Uchida et al., J. Virol. 86:2686–2695, 2012, doi:http://dx.doi.org/10.1128/JVI.06374-11). In the present study, we introduced a C38Y substitution into WB PB1 and demonstrated that this substitution increased both polymerase activity in DF-1 cells in vitro and the pathogenicity of the recombinant viruses in chickens. The V14A substitution in LP PB1 reduced polymerase activity but did not affect pathogenicity in chickens. Interestingly, the V14A substitution reduced viral shedding and transmissibility. These studies demonstrate that increased polymerase activity correlates directly with enhanced pathogenicity, while decreased polymerase activity does not always correlate with pathogenicity and requires further analysis. IMPORTANCE We identified 2 novel amino acid substitutions in the avian influenza virus PB1 gene that affect the characteristics of highly pathogenic avian influenza viruses (HPAIVs) of the H5N1 subtype, such as viral replication and polymerase activity in vitro and pathogenicity and transmissibly in chickens. An amino acid substitution at residue 38 in PB1 directly affected pathogenicity in chickens and was associated with changes in polymerase activity in vitro. A substitution at residue 14 reduced polymerase activity in vitro, while its effects on pathogenicity and transmissibility depended on the constellation of internal genes. PMID:25031333

  3. Molecular modelling study of the 3D structure of the bovine viral diarrhea virus (BVDV) helicase.

    PubMed

    Brancale, Andrea; Vlachaki, Chrisanthy; Vlachakis, Dimitrios

    2008-01-01

    Bovine viral diarrhea virus (BVDV) is a member of the Flaviviridae family of viruses and constitutes a very important pathogen for livestock around the world. The viral helicase is an enzyme essential for the proliferation and transmission of the virus. In this work a 3D-model of the BVDV helicase was produced using homology modelling techniques and the known 3D-structure of the hepatitis C helicase of the Flaviviridae family as template, in an attempt to provide the means for structure-based design of novel anti-BVDV agents. PMID:19374131

  4. Eicosanoids and Respiratory Viral Infection: Coordinators of Inflammation and Potential Therapeutic Targets

    PubMed Central

    McCarthy, Mary K.; Weinberg, Jason B.

    2012-01-01

    Viruses are frequent causes of respiratory infection, and viral respiratory infections are significant causes of hospitalization, morbidity, and sometimes mortality in a variety of patient populations. Lung inflammation induced by infection with common respiratory pathogens such as influenza and respiratory syncytial virus is accompanied by increased lung production of prostaglandins and leukotrienes, lipid mediators with a wide range of effects on host immune function. Deficiency or pharmacologic inhibition of prostaglandin and leukotriene production often results in a dampened inflammatory response to acute infection with a respiratory virus. These mediators may, therefore, serve as appealing therapeutic targets for disease caused by respiratory viral infection. PMID:22665949

  5. Revealing the density of encoded functions in a viral RNA

    PubMed Central

    Patel, Nikesh; Dykeman, Eric C.; Coutts, Robert H. A.; Lomonossoff, George P.; Rowlands, David J.; Phillips, Simon E. V.; Ranson, Neil; Twarock, Reidun; Tuma, Roman; Stockley, Peter G.

    2015-01-01

    We present direct experimental evidence that assembly of a single-stranded RNA virus occurs via a packaging signal-mediated mechanism. We show that the sequences of coat protein recognition motifs within multiple, dispersed, putative RNA packaging signals, as well as their relative spacing within a genomic fragment, act collectively to influence the fidelity and yield of capsid self-assembly in vitro. These experiments confirm that the selective advantages for viral yield and encapsidation specificity, predicted from previous modeling of packaging signal-mediated assembly, are found in Nature. Regions of the genome that act as packaging signals also function in translational and transcriptional enhancement, as well as directly coding for the coat protein, highlighting the density of encoded functions within the viral RNA. Assembly and gene expression are therefore direct molecular competitors for different functional folds of the same RNA sequence. The strongest packaging signal in the test fragment, encodes a region of the coat protein that undergoes a conformational change upon contact with packaging signals. A similar phenomenon occurs in other RNA viruses for which packaging signals are known. These contacts hint at an even deeper density of encoded functions in viral RNA, which if confirmed, would have profound consequences for the evolution of this class of pathogens. PMID:25646435

  6. Signaling During Pathogen Infection

    NSDL National Science Digital Library

    Sylvia Munter (University of Heidelberg Medical School; Department of Parasitology REV)

    2006-05-16

    Pathogens infect almost every living organism. In animals, including humans, the diversity of pathogens ranges from viruses, bacteria, and unicellular parasites to complex fungi, worms, and arthropods. Because pathogens have coevolved with their hosts and have sometimes been coopted as symbionts or commensals, each pathogen/host pair represents a striking success story of survival that reflects the biological complexity of both parties. All invading microorganisms face similar problems, such as gaining access to their host, achieving successful replication, and spreading to a similar or different host. It is therefore not surprising that many different pathogens target similar organs, cell types, and even molecules to achieve their goals. However, no two microbial parasites appear to be completely alike. Although they often target similar signaling networks, they do so in subtly different ways to achieve the desired outcome. This review has eight figures, three movies, and 139 citations and emphasizes two well-established signaling pathways that are often activated during the interaction of different pathogens with their host cells. It illustrates a small part of how the dissection of host/pathogen interactions can reveal, on a molecular scale, a nature shaped by evolutionary forces that can rival the great descriptions of our macroscopic world.

  7. Diversity and composition of viral communities: coinfection of barley and cereal yellow dwarf viruses in California grasslands.

    PubMed

    Seabloom, Eric W; Hosseini, Parviez R; Power, Alison G; Borer, Elizabeth T

    2009-03-01

    Most species host multiple pathogens, yet field studies rarely examine the processes determining pathogen diversity within a single host or the effects of coinfection on pathogen dynamics in natural systems. Coinfection can affect pathogen transmission and virulence. In turn, coinfection can be regulated within hosts by interactions such as cross-protective immunity or at broader spatial scales via vector distributions. Using a general model, we demonstrate that coinfection by a group of vectored pathogens is highest with abundant generalist vectors and weak cross-protection and coinfection-induced mortality. Using these predictions, we investigate the distribution of five coexisting aphid-vectored, viral pathogens (barley and cereal yellow dwarf luteoviruses and poleroviruses) in a native perennial grass (Elymus glaucus) in both space (700 km) and time (4 years). Observed coinfection rates were much higher than expected at random, suggesting that within-host processes exerted weak effects on within-host pathogen diversity. Covariance among viruses in space and time was highest for viral species sharing a vector. Temporal correlation arose from the synchronous invasion of two viruses transmitted by a shared aphid species. On the basis of our modeling and empirical results, we expect that factors external to individual hosts may affect the coinfection dynamics in other communities hosting vectored pathogens. PMID:19183066

  8. A study on pathogens of Chinese prawn ( Penaeus Chinensis) virus diseases

    NASA Astrophysics Data System (ADS)

    Sun, Xiu-Qin; Zhang, Jin-Xing

    1995-09-01

    This pathogenic study shows that the viral diseases of Chinese prawns ( Penaeus chinensis, O'sbeck) is due to three kinds of viruses: epithelium envelope baculovirus of Penaeus chinensis (EEBV-PC, detected by the authors in 1993), infections hypodermal and hematopoietic necrosis virus, and hepatopancreatic parvo-like virus, and that the first two viruses seem to be the main pathogens of the epidemic in the northern regions in 1993.

  9. Pathogenic and Host Range Determinants of the Feline Aplastic Anemia Retrovirus

    Microsoft Academic Search

    Norbert Riedel; Edward A. Hoover; Ronna E. Dornsife; James I. Mullins

    1988-01-01

    Feline leukemia virus (FeLV) C-Sarma (or FSC) is a prototype of subgroup C FeLVs, which induce fatal aplastic anemia in outbred specific-pathogen-free (SPF) cats. FeLV C isolates also possess an extended host range in vitro, including an ability, unique among FeLVs, to replicate in guinea pig cells. To identify the viral determinants responsible for the pathogenicity and host range of

  10. The Dynamics of Viral Marketing JURE LESKOVEC

    E-print Network

    Pratt, Vaughan

    - ing such as TV or newspaper ads, marketers have turned to alternate strategies, including viral that "there needs to be a greater understanding of the contexts in which viral marketing strategy works and The Dynamics of Viral Marketing JURE LESKOVEC Carnegie Mellon University LADA A. ADAMIC University

  11. Viral replication and genetics Nabil A. NIMER

    E-print Network

    the enzymes necessary to replicate viral DNA viral RNA. #12;#12;A fundamental difference between the replication of viruses and bacteria; the latter retain their structure and infectivity throughout the growth. #12;General plan of viral replication No single virus is typical of them all. We have chosen a DNA

  12. Viral Video Style: A Closer Look at Viral Videos on YouTube

    E-print Network

    Shamos, Michael I.

    Viral Video Style: A Closer Look at Viral Videos on YouTube Lu Jiang, Yajie Miao, Yi Yang Introduction CMU Viral Video Dataset Statistical Characteristics Peak Day Prediction Conclusions #12;Outline Introduction CMU Viral Video Dataset Statistical Characteristics Peak Day Prediction

  13. Immune response genes and pathogen presence predict migration survival in wild salmon smolts.

    PubMed

    Jeffries, Ken M; Hinch, Scott G; Gale, Marika Kirstin; Clark, Timothy D; Lotto, Andrew G; Casselman, Matthew T; Li, Shaorong; Rechisky, Erin L; Porter, Aswea D; Welch, David W; Miller, Kristina M

    2014-12-01

    We present the first data to link physiological responses and pathogen presence with subsequent fate during migration of wild salmonid smolts. We tagged and non-lethally sampled gill tissue from sockeye salmon (Oncorhynchus nerka) smolts as they left their nursery lake (Chilko Lake, BC, Canada) to compare gene expression profiles and freshwater pathogen loads with migration success over the first ~1150 km of their migration to the North Pacific Ocean using acoustic telemetry. Fifteen per cent of smolts were never detected again after release, and these fish had gene expression profiles consistent with an immune response to one or more viral pathogens compared with fish that survived their freshwater migration. Among the significantly upregulated genes of the fish that were never detected postrelease were MX (interferon-induced GTP-binding protein Mx) and STAT1 (signal transducer and activator of transcription 1-alpha/beta), which are characteristic of a type I interferon response to viral pathogens. The most commonly detected pathogen in the smolts leaving the nursery lake was infectious haematopoietic necrosis virus (IHNV). Collectively, these data show that some of the fish assumed to have died after leaving the nursery lake appeared to be responding to one or more viral pathogens and had elevated stress levels that could have contributed to some of the mortality shortly after release. We present the first evidence that changes in gene expression may be predictive of some of the freshwater migration mortality in wild salmonid smolts. PMID:25354752

  14. Potentiation of anthrax vaccines using protective antigen-expressing viral replicon vectors.

    PubMed

    Wang, Hai-Chao; An, Huai-Jie; Yu, Yun-Zhou; Xu, Qing

    2015-02-01

    DNA vaccines require improvement for human use because they are generally weak stimulators of the immune system in humans. The efficacy of DNA vaccines can be improved using a viral replicon as vector to administer antigen of pathogen. In this study, we comprehensively evaluated the conventional non-viral DNA, viral replicon DNA or viral replicon particles (VRP) vaccines encoding different forms of anthrax protective antigen (PA) for specific immunity and protective potency against anthrax. Our current results clearly suggested that these viral replicon DNA or VRP vaccines derived from Semliki Forest virus (SFV) induced stronger PA-specific immune responses than the conventional non-viral DNA vaccines when encoding the same antigen forms, which resulted in potent protection against challenge with the Bacillus anthracis strain A16R. Additionally, the naked PA-expressing SFV replicon DNA or VRP vaccines without the need for high doses or demanding particular delivery regimens elicited robust immune responses and afforded completely protective potencies, which indicated the potential of the SFV replicon as vector of anthrax vaccines for use in clinical application. Therefore, our results suggest that these PA-expressing SFV replicon DNA or VRP vaccines may be suitable as candidate vaccines against anthrax. PMID:25102364

  15. Influence of temperature on viral hemorrhagic septicemia (Genogroup IVa) in Pacific herring, Clupea pallasii Valenciennes

    USGS Publications Warehouse

    Hershberger, P.K.; Purcell, M.K.; Hart, L.M.; Gregg, J.L.; Thompson, R.L.; Garver, K.A.; Winton, J.R.

    2013-01-01

    An inverse relationship between water temperature and susceptibility of Pacific herring (Clupea pallasii) to viral hemorrhagic septicemia, genogroup IVa (VHS) was indicated by controlled exposure studies where cumulative mortalities, viral shedding rates, and viral persistence in survivors were greatest at the coolest exposure temperatures. Among groups of specific pathogen-free (SPF) Pacific herring maintained at 8, 11, and 15 °C, cumulative mortalities after waterborne exposure to viral hemorrhagic septicemia virus (VHSV) were 78%, 40%, and 13%, respectively. The prevalence of survivors with VHSV-positive tissues 25 d post-exposure was 64%, 16%, and 0% (at 8, 11 and 15 °C, respectively) with viral prevalence typically higher in brain tissues than in kidney/spleen tissue pools at each temperature. Similarly, geometric mean viral titers in brain tissues and kidney/spleen tissue pools decreased at higher temperatures, and kidney/spleen titers were generally 10-fold lower than those in brain tissues at each temperature. This inverse relationship between temperature and VHS severity was likely mediated by an enhanced immune response at the warmer temperatures, where a robust type I interferon response was indicated by rapid and significant upregulation of the herring Mx gene. The effect of relatively small temperature differences on the susceptibility of a natural host to VHS provides insights into conditions that preface periodic VHSV epizootics in wild populations throughout the NE Pacific.

  16. Proteomics of bacterial pathogens.

    PubMed

    Cash, Phillip

    2003-01-01

    The rapid growth of proteomics that has been built upon the available bacterial genome sequences has opened provided new approaches to the analysis of bacterial functional genomics. In the study of pathogenic bacteria the combined technologies of genomics, proteomics and bioinformatics has provided valuable tools for the study of complex phenomena determined by the action of multiple gene sets. The review considers some of the recent developments in the establishment of proteomic databases as well as attempts to define pathogenic determinants at the level of the proteome for some of the major human pathogens. Proteomics can also provide practical applications through the identification of immunogenic proteins that may be potential vaccine targets as well as in extending our understanding of antibiotic action. There is little doubt that proteomics has provided us with new and valuable information on bacterial pathogens and will continue to be an important source of information in the coming years. PMID:12934927

  17. Human Pathogen Importation Importing "Human" Pathogens from Outside Canada

    E-print Network

    Human Pathogen Importation Importing "Human" Pathogens from Outside Canada 1) Permits.gc.ca/ols-bsl/pathogen/index.html and scroll to the bottom of the page where you can download the "Application for Permit to Import Human Human Pathogens" and "CL2 Checklist" to PHAC at (613) 941-0596. There are no fees for this service. 5

  18. Histone deacetylases in viral infections

    Microsoft Academic Search

    Georges Herbein; Daniel Wendling

    2010-01-01

    Chromatin remodeling and gene expression are regulated by histone deacetylases (HDACs) that condense the chromatin structure\\u000a by deacetylating histones. HDACs comprise a group of enzymes that are responsible for the regulation of both cellular and\\u000a viral genes at the transcriptional level. In mammals, a total of 18 HDACs have been identified and grouped into four classes,\\u000a i.e., class I (HDACs

  19. [How the bovine viral diarrhea virus outwits the immune system].

    PubMed

    Peterhans, E; Jungi, T W; Schweizer, M

    2006-04-01

    The interaction of bovine viral diarrhea virus (BVD virus) with its host has several unique features, most notably the capacity to infect its host either transiently or persistently. The transient infection stimulates an antiviral immune reaction similar to that seen in other transient viral infections. In contrast, being associated with immunotolerance specific for the infecting BVD viral strain, the persistent infection differs fundamentally from other persistent infections like those caused by lentiviruses. Whereas the latter are characterized by complex viral evasion of the host's adaptive immune response by mechanisms such as antigenic drift and interference with presentation of T cell epitopes, BVD virus avoids the immune response altogether by inducing both humoral and cellular immune tolerance. This is made possible by invasion of the fetus at an early stage of development. In addition to adaptive immunity, BVD virus also manipulates key elements of the host's innate immune response. The non-cytopathic biotype of BVD virus, which is capable of persistently infecting its host, fails to induce type I interferon. In addition, persistently infected cells are resistant to the induction of apoptosis by double-stranded RNA and do not produce interferon when treated with this pathogen-associated molecular pattern (PAMP) that signals viral infection. Moreover, when treated with interferon, cells persistently infected with non-cytopathic BVD virus do not clear the virus. Surprisingly, however, despite this lack of effect on persistent infection, interferon readily induces an antiviral state in these cells, as shown by the protection against infection by unrelated viruses. Overall, BVD virus manipulates the host's interferon defense in a manner that optimises its chances of maintaining the persistent infection as well as decreasing the risks that heterologous viral infections may carry for the host. Thus, since not all potential host cells are infected in animals persistently infected with BVD virus, heterologous viruses replicating in cells uninfected with BVD virus will still trigger production of interferon. Interferon produced by such cells will curtail the replication of heterologous viruses only, be that in cells already infected with BVD virus, or in cells in which the heterologous virus may replicate alone. From an evolutionary viewpoint, this strategy clearly enhances the chances of transmission of BVD virus to new hosts, as it attenuates the negative effects that a global immunosuppression would have on the survival of persistently infected animals. PMID:16716045

  20. Activation of cell signaling pathways is dependant on the biotype of bovine viral diarrhea viruses type 2

    Microsoft Academic Search

    S. Bendfeldt; J. F. Ridpath; J. D. Neill

    2007-01-01

    Bovine viral diarrhea virus (BVDV), a pestivirus of the Flaviviridae family, is an economically important cattle pathogen with a worldwide distribution. Besides the segregation into two distinct species (BVDV1\\/BVDV2) two different biotypes, a cytopathic (cp) and a noncytopathic (ncp) biotype, are distinguished based on their behavior in epithelial cell cultures. One of the most serious forms of BVDV infection affecting

  1. A Nuclear Localization of the Infectious Haematopoietic Necrosis Virus NV Protein Is Necessary for Optimal Viral Growth

    Microsoft Academic Search

    Myeong Kyu Choi; Chang Hoon Moon; Myoung Seok Ko; Unn-Hwa Lee; Wha Ja Cho; Seung Ju Cha; Jeong Wan Do; Gang Joon Heo; Soo Geun Jeong; Yoo Sik Hahm; Abdallah Harmache; Michel Bremont; Gael Kurath; Jeong Woo Park

    2011-01-01

    The nonvirion (NV) protein of infectious hematopoietic necrosis virus (IHNV) has been previously reported to be essential for efficient growth and pathogenicity of IHNV. However, little is known about the mechanism by which the NV supports the viral growth. In this study, cellular localization of NV and its role in IHNV growth in host cells was investigated. Through transient transfection

  2. Investigating the complex viral community of the turkey gut: an update from the laboratory and the field

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Periodic monitoring of poultry flocks in the United States via molecular diagnostic methods has revealed a number of potential enteric viral pathogens in continuous circulation in turkeys and chickens. Recently, numerous enteric samples collected from turkey flocks in the southeastern United States ...

  3. Transmission of Bovine Viral Diarrhea Virus from Acutely Infected White Tailed Deer to Cattle via Indirect Contact

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea viruses (BVDV) are found worldwide, and acute infections in cattle results in enteric, respiratory, and reproductive diseases of varying severity, depending on the BVDV strain, the immune and reproductive status of the host and the presence of secondary pathogens. While most c...

  4. Comparison of the Immune Response Between a Pair of NCP and CP Bovine Viral Diarrhea Virus (BVDV) Type 1 Isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aim: Bovine viral diarrhea virus (BVDV) is a major pathogen of cattle causing severe respiratory and reproductive disease. BVDV vaccines remain an important part of the control strategy. Previous work has described higher antibody responses in animals infected with a noncytopathic (NCP) BVDV when ...

  5. Comparison of the immune response between a pair of NCP and CP bovine viral diarrhea virus (BVDV) type 1 isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) is a major pathogen of cattle causing severe respiratory and reproductive disease. BVDV vaccines remain an important part of the control strategy. Previous work has described higher antibody responses in animals infected with a noncytopathic (NCP) BVDV when compa...

  6. Histophathologic and Immunohistochemical Findings in Two White-tail Deer Fawns Persistently Infected with Bovine Viral Diarrhea Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) is an important pathogen of domestic cattle. Serological, experimental and individual case studies have explored the presence and pathogenesis of the virus in wild ungulates; however there remain large gaps in knowledge regarding BVDV infection in non-bovine speci...

  7. Activation of cell signaling pathways is dependant on the biotype of bovine viral diarrhea virus type 2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV), a pestivirus of the Flaviviridae family, is an economically important cattle pathogen with a world wide distribution. Besides the segregation into two distinct species (BVDV1 / BVDV2) two different biotypes, a cytopathic (cp) and a noncytopathic (ncp) biotype, are...

  8. Surface-enhanced Raman scattering (SERS) detection of multiple viral antigens using magnetic capture of SERS-active nanoparticles.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A highly sensitive immunoassay based on surface-enhanced Raman scattering (SERS) spectroscopy has been developed for multiplex detection of surface envelope and capsid antigens of the viral zoonotic pathogens West Nile virus (WNV) and Rift Valley fever virus (RVFV). Detection was mediated by antibo...

  9. 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

  10. Evaluation of the presence of equine viral herpesvirus 1 (EHV-1) and equine viral herpesvirus 4 (EHV-4) DNA in stallion semen using polymerase chain reaction (PCR).

    PubMed

    Hebia-Fellah, Imen; Léauté, Anne; Fiéni, Francis; Zientara, Stéphan; Imbert-Marcille, Berthe-Marie; Besse, Bernard; Fortier, Guillaume; Pronost, Stephane; Miszczak, Fabien; Ferry, Bénédicte; Thorin, Chantal; Pellerin, Jean-Louis; Bruyas, Jean-François

    2009-06-01

    In the horse, the risk of excretion of two major equine pathogens (equine herpesvirus types 1 (EHV-1) and 4 (EHV-4)) in semen is unknown. The objective of our study was to assess the possible risks for the horizontal transmission of equine rhinopneumonitis herpesviruses via the semen and the effect of the viruses on stallion fertility. Samples of stallion semen (n=390) were gathered from several different sources. Examination of the semen involved the detection of viral DNA using specific PCR. The mean fertility of the stallions whose sperm tested positive for viral DNA and the mean fertility of stallions whose sperm did not contain viral DNA, were compared using the Student's t-test. EHV-4 viral DNA was not detected in any of the semen samples. EHV-1 DNA was identified in 51 of the 390 samples, (13%). One hundred and eighty-two samples came from 6 studs and there was significant difference (p<0.05) among the proportion of stallions whose semen tested positive for viral DNA from 0 to 55% between the studs. There was a significant difference (p<0.014) between the fertility of stallions whose semen tested positive for viral DNA and those whose semen was free from viral DNA. The stallions that excreted the EHV-1 virus in their semen appeared to be more fertile than the non-excretors, but this difference was in fact related to the breeding technique since higher proportion of excretors were found among those whose semen was used fresh rather than preserved by cooling or freezing. In conclusion, this study suggests that the EHV-1 virus may be transmitted via the semen at mating or by artificial insemination as demonstrated with other herpes viruses in other species. PMID:19268345

  11. Lactoferrin-derived resistance against plant pathogens in transgenic plants.

    PubMed

    Lakshman, Dilip K; Natarajan, Savithiry; Mandal, Sudhamoy; Mitra, Amitava

    2013-12-01

    Lactoferrin (LF) is a ubiquitous cationic iron-binding milk glycoprotein that contributes to nutrition and exerts a broad-spectrum primary defense against bacteria, fungi, protozoa, and viruses in mammals. These qualities make lactoferrin protein and its antimicrobial motifs highly desirable candidates to be incorporated in plants to impart broad-based resistance against plant pathogens or to economically produce them in bulk quantities for pharmaceutical and nutritional purposes. This study introduced bovine LF (BLF) gene into tobacco ( Nicotiana tabacum var. Xanthi), Arabidopsis ( A. thaliana ) and wheat ( Triticum aestivum ) via Agrobacterium -mediated plant transformation. Transgenic plants or detached leaves exhibited high levels of resistance against the damping-off causing fungal pathogen Rhizoctonia solani and the head blight causing fungal pathogen Fusarium graminearum . LF also imparted resistance to tomato plants against a bacterial pathogen, Ralstonia solanacearum . Similarly, other researchers demonstrated expression of LF and LF-mediated high-quality resistance to several other aggressive fungal and bacterial plant pathogens in transgenic plants and against viral pathogens by foliar applications of LF or its derivatives. Taken together, these studies demonstrated the effectiveness of LF for improving crop quality and its biopharming potentials for pharmaceautical and nutritional applications. PMID:23889215

  12. Caenorhabditis elegans as a model for intracellular pathogen infection

    PubMed Central

    Balla, Keir M.; Troemel, Emily R.

    2014-01-01

    Summary The genetically tractable nematode Caenorhabditis elegans is a convenient host for studies of pathogen infection. With the recent identification of two types of natural intracellular pathogens of C. elegans, this host now provides the opportunity to examine interactions and defence against intracellular pathogens in a whole-animal model for infection. C. elegans is the natural host for a genus of microsporidia, which comprise a phylum of fungal-related pathogens of widespread importance for agriculture and medicine. More recently, C. elegans has been shown to be a natural host for viruses related to the Nodaviridae family. Both microsporidian and viral pathogens infect the C. elegans intestine, which is composed of cells that share striking similarities to human intestinal epithelial cells. Because C. elegans nematodes are transparent, these infections provide a unique opportunity to visualize differentiated intestinal cells in vivo during the course of intracellular infection. Together, these two natural pathogens of C. elegans provide powerful systems in which to study microbial pathogenesis and host responses to intracellular infection. PMID:23617769

  13. Caenorhabditis elegans as a model for intracellular pathogen infection.

    PubMed

    Balla, Keir M; Troemel, Emily R

    2013-08-01

    The genetically tractable nematode Caenorhabditis elegans is a convenient host for studies of pathogen infection. With the recent identification of two types of natural intracellular pathogens of C. elegans, this host now provides the opportunity to examine interactions and defence against intracellular pathogens in a whole-animal model for infection. C. elegans is the natural host for a genus of microsporidia, which comprise a phylum of fungal-related pathogens of widespread importance for agriculture and medicine. More recently, C. elegans has been shown to be a natural host for viruses related to the Nodaviridae family. Both microsporidian and viral pathogens infect the C. elegans intestine, which is composed of cells that share striking similarities to human intestinal epithelial cells. Because C. elegans nematodes are transparent, these infections provide a unique opportunity to visualize differentiated intestinal cells in vivo during the course of intracellular infection. Together, these two natural pathogens of C. elegans provide powerful systems in which to study microbial pathogenesis and host responses to intracellular infection. PMID:23617769

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

    PubMed

    Shekhar, M S; Ponniah, A G

    2014-06-23

    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. PMID:24953507

  15. Tickling the TLR7 to cure viral hepatitis

    PubMed Central

    2014-01-01

    Chronic hepatitis B and C are the leading causes of liver disease and liver transplantation worldwide. Ability to mount an effective immune response against both HBV and HCV is associated with spontaneous clearance of both infections, while an inability to do so leads to chronicity of both infections. To mount an effective immune response, both innate and adaptive immune responses must work in tandem. Hence, developing protective immunity to hepatitis viruses is an important goal in order to reduce the global burden of these two infections and prevent development of long-term complications. In this regard, the initial interactions between the pathogen and immune system are pivotal in determining the effectiveness of immune response and subsequent elimination of pathogens. Toll-like receptors (TLRs) are important regulators of innate and adaptive immune responses to various pathogens and are often involved in initiating and augmenting effective antiviral immunity. Immune-based therapeutic strategies that specifically induce type I interferon responses are associated with functional cure for both chronic HBV and HCV infections. Precisely, TLR7 stimulation mediates an endogenous type I interferon response, which is critical in development of a broad, effective and protective immunity against hepatitis viruses. This review focuses on anti-viral strategies that involve targeting TLR7 that may lead to development of protective immunity and eradication of hepatitis B. PMID:24884741

  16. Selective Expansion of Viral Variants following Experimental Transmission of a Reconstituted Feline Immunodeficiency Virus Quasispecies

    PubMed Central

    Willett, Brian J.; Kraase, Martin; Logan, Nicola; McMonagle, Elizabeth; Varela, Mariana; Hosie, Margaret J.

    2013-01-01

    Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV), a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1) or diverse (Group 2) challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point) being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development. PMID:23372784

  17. The contribution of molecular epidemiology to the understanding and control of viral diseases of salmonid aquaculture

    PubMed Central

    2011-01-01

    Molecular epidemiology is a science which utilizes molecular biology to define the distribution of disease in a population (descriptive epidemiology) and relies heavily on integration of traditional (or analytical) epidemiological approaches to identify the etiological determinants of this distribution. The study of viral pathogens of aquaculture has provided many exciting opportunities to apply such tools. This review considers the extent to which molecular epidemiological studies have contributed to better understanding and control of disease in aquaculture, drawing on examples of viral diseases of salmonid fish of commercial significance including viral haemorrhagic septicaemia virus (VHSV), salmonid alphavirus (SAV) and infectious salmon anaemia virus (ISAV). Significant outcomes of molecular epidemiological studies include: Improved taxonomic classification of viruses A better understanding of the natural distribution of viruses An improved understanding of the origins of viral pathogens in aquaculture An improved understanding of the risks of translocation of pathogens outwith their natural host range An increased ability to trace the source of new disease outbreaks Development of a basis for ensuring development of appropriate diagnostic tools An ability to classify isolates and thus target future research aimed at better understanding biological function While molecular epidemiological studies have no doubt already made a significant contribution in these areas, the advent of new technologies such as pyrosequencing heralds a quantum leap in the ability to generate descriptive molecular sequence data. The ability of molecular epidemiology to fulfil its potential to translate complex disease pathways into relevant fish health policy is thus unlikely to be limited by the generation of descriptive molecular markers. More likely, full realisation of the potential to better explain viral transmission pathways will be dependent on the ability to assimilate and analyse knowledge from a range of more traditional information sources. The development of methods to systematically record and share such epidemiologically important information thus represents a major challenge for fish health professionals in making the best future use of molecular data in supporting fish health policy and disease control. PMID:21466673

  18. Viral-templated Palladium Nanocatalysts

    NASA Astrophysics Data System (ADS)

    Yang, Cuixian

    Despite recent progress on nanocatalysis, there exist several critical challenges in simple and readily controllable nanocatalyst synthesis including the unpredictable particle growth, deactivation of catalytic activity, cumbersome catalyst recovery and lack of in-situ reaction monitoring. In this dissertation, two novel approaches are presented for the fabrication of viral-templated palladium (Pd) nanocatalysts, and their catalytic activities for dichromate reduction reaction and Suzuki Coupling reaction were thoroughly studied. In the first approach, viral template based bottom-up assembly is employed for the Pd nanocatalyst synthesis in a chip-based format. Specifically, genetically displayed cysteine residues on each coat protein of Tobacco Mosaic Virus (TMV) templates provide precisely spaced thiol functionalities for readily controllable surface assembly and enhanced formation of catalytically active Pd nanoparticles. Catalysts with the chip-based format allow for simple separation and in-situ monitoring of the reaction extent. Thorough examination of synthesis-structure-activity relationship of Pd nanoparticles formed on surface-assembled viral templates shows that Pd nanoparticle size, catalyst loading density and catalytic activity of viral-templated Pd nanocatalysts can be readily controlled simply by tuning the synthesis conditions. The viral-templated Pd nanocatalysts with optimized synthesis conditions are shown to have higher catalytic activity per unit Pd mass than the commercial Pd/C catalysts. Furthermore, tunable and selective surface assembly of TMV biotemplates is exploited to control the loading density and location of Pd nanocatalysts on solid substrates via preferential electroless deposition. In addition, the catalytic activities of surface-assembled TMV-templated Pd nanocatalysts were also investigated for the ligand-free Suzuki Coupling reaction under mild reaction conditions. The chip-based format enables simple catalyst separation and reuse as well as facile product recovery. Reaction condition studies show that the solvent ratio played an important role in the selectivity of the Suzuki reaction, and that a higher water/acetonitrile ratio significantly facilitated the cross-coupling pathway. Meanwhile, in-depth characterizations including Atomic Force Microscopy (AFM), Grazing Incidence Small Angle X-ray Scattering (GISAXS), Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) and X-ray Photoelectron Spectroscopy (XPS) were carried out for these chip-based viral-templated Pd nanocatalysts. In the second approach, catalytically active TMV-templated Pd nanoparticles are encapsulated in readily exploited polymeric microparticle formats. Specifically, small (1˜2 nm), uniform and highly crystalline palladium (Pd) nanoparticles are spontaneously formed along (TMV) biotemplates without external reducing agents. The as-prepared Pd-TMV complexes are integrated into the hybrid poly(ethylene glycol)(PEG)-based microparticles via replica molding (RM) technique in a simple, robust and highly reproducible manner. The Pd-TMV complex structure was characterized by Transmission Electron Microscopy (TEM). The hybrid Pd-TMV-PEG microparticles are examined to have high catalytic activity, recyclability and stability through dichromate reduction. Combined these findings represent a significant step toward simple, robust, scalable synthesis and fabrication of efficient biotemplate-supported Pd nanocatalysts in readily deployable polymeric formats with high capacity in a well-controlled manner. These two simple, robust and readily controllable approaches for the fabrication of viral-templated Pd nanocatalysts, in both chip-based and hydrogel-encapsulated formats, can be readily extended to a variety of other nano-bio hybrid material synthesis in other catalytic reaction systems.

  19. Relating Structure to Evolution in Class II Viral Membrane Fusion Proteins

    PubMed Central

    Modis, Yorgo

    2014-01-01

    Enveloped viruses must fuse their lipid membrane to a cellular membrane to deliver the viral genome into the cytoplasm for replication. Viral envelope proteins catalyze this critical membrane fusion event. They fall into at least three distinct structural classes. Class II fusion proteins have a conserved three-domain architecture and are found in many important viral pathogens. Until 2013, class II proteins had only been found in flaviviruses and alphaviruses. However, in 2013 a class II fusion protein was discovered in the unrelated phlebovirus genus, and two unexpectedly divergent envelope proteins were identified in families that also contain prototypical class II proteins. The structural relationships of newly identified class II proteins, reviewed herein, shift the paradigm for how these proteins evolved. PMID:24525225

  20. Immediate early responses of avian tracheal epithelial cells to infection with highly pathogenic avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic (HP) avian influenza viruses (AIV) present an on going threat to the U.S. poultry industry. In order to develop new AIV control strategies it is necessary to understand the underlying mechanism of viral infection. Because the early events of AIV infection can occur on tracheal ep...

  1. The role of eriophyoids in fungal pathogen epidemiology, mere association or true interaction?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A considerable number of plant feeding mites representing different families such as Acaridae, Siteroptidae, Tydeidae and Tarsonemidae interact with plant pathogenic fungi. While species within the Eriophyoidea appear to be the most common phytophagous mites vectoring viral diseases little is known ...

  2. Life-History Responses to Pathogens in Tiger Salamander (Ambystoma tigrinum) Larvae

    E-print Network

    Storfer, Andrew

    Life-History Responses to Pathogens in Tiger Salamander (Ambystoma tigrinum) Larvae MATTHEW J the presence of an iridovirus (Ambystoma tigrinum virus; ATV) could alter patterns of larval life histories in Arizona Tiger Salamanders (Ambystoma tigrinum nebulosum). Viral epidemics cause extreme mortality

  3. Survey of Salmonid Pathogens in Ocean-Caught Fishes in British Columbia, Canada

    Microsoft Academic Search

    M. L. Kent; G. S. Traxler; D. Kieser; J. Richard; S. C. Dawe; R. W. Shaw; G. Prosperi-Porta; J. Ketcheson; T. P. T. Evelyn

    1998-01-01

    A survey of wild fishes captured around marine net-pen salmon farms and from open waters for certain salmonid pathogens was conducted in the coastal waters of British Columbia. Viral hemorrhagic septicemia virus was detected in Pacific herring Clupea pallasi, shiner perch Cymatogaster aggregata, and threespine sticklebacks Gasterosteus aculeatus. Infectious hematopoietic necrosis (IHN) virus was detected in one Pacific herring (collected

  4. Metagenomic Analysis of the Viral Flora of Pine Marten and European Badger Feces

    PubMed Central

    van den Brand, Judith M. A.; van Leeuwen, Marije; Schapendonk, Claudia M.; Simon, James H.; Haagmans, Bart L.; Osterhaus, Albert D. M. E.

    2012-01-01

    A thorough understanding of the diversity of viruses in wildlife provides epidemiological baseline information about potential pathogens. Metagenomic analysis of the enteric viral flora revealed a new anellovirus and bocavirus species in pine martens and a new circovirus-like virus and geminivirus-related DNA virus in European badgers. In addition, sequences with homology to viruses from the families Paramyxo- and Picornaviridae were detected. PMID:22171250

  5. Bovine viral diarrhea virus: Its effects on estradiol, progesterone and prostaglandin secretion in the cow

    Microsoft Academic Search

    M. D. Fray; G. E. Mann; M. C. Clarke; B. Charleston

    1999-01-01

    Bovine viral diarrhea virus (BVDV) is a major cattle pathogen responsible for a spectrum of symptoms, including reproductive failure. This study was designed to establish the effects of BVDV infection on estradiol, progesterone and PGF2alpha secretion in the cow. Seven BVDV-free cows were challenged with non-cytopathogenic BVDV (strain Pe 515: 5sx106tissue culture infected dose50) so that peak viremia occurred during

  6. Quality controls for bovine viral diarrhea virus-free IVF embryos

    Microsoft Academic Search

    D. A. Stringfellow; K. P. Riddell; P. K. Galik; P. Damiani; M. D. Bishop; J. C. Wright

    2000-01-01

    Introduction of bovine viral diarrhea virus (BVDV) with cumulus-oocyte-complexes (COCs) from the abattoir is a concern in the production of bovine embryos in vitro. Further, International Embryo Transfer Society (IETS) guidelines for washing and trypsin treatment of invivo-derived bovine embryos ensure freedom from a variety of pathogens, but these procedures appear to be less effective when applied to IVF embryos.

  7. Viral RNA-polymerases – a predicted 2?-O-ribose methyltransferase domain shared by all Mononegavirales

    Microsoft Academic Search

    François Ferron; Sonia Longhi; Bernard Henrissat; Bruno Canard

    2002-01-01

    The Mononegavirales virus group comprises several major human pathogens, including measles, rabies and Ebola viruses. This article reports a computational analysis of the C-terminal region of RNA-dependent RNA-polymerases from Mononegavirales. Using a combination of sequence similarity and threading analysis, a 2?-O-ribose methyltransferase domain was identified that is involved in the capping of viral mRNAs.

  8. Viral Factors Determine Progression to AIDS in Simian Immunodeficiency Virus-Infected Newborn Rhesus Macaques

    Microsoft Academic Search

    MARTA L. MARTHAS; KOEN K. A. VAN ROMPAY; MOSES OTSYULA; CHRISTOPHER J. MILLER; DON R. CANFIELD; NIELS C. PEDERSEN; ANDMICHAEL B. MCCHESNEY

    1995-01-01

    To evaluate how viral variants may affect disease progression in human pediatric AIDS, we studied the potential of three simian immunodeficiency virus (SIV) isolates to induce simian AIDS in newborn rhesus macaques. The three virus isolates were previously shown to range from pathogenic (SIVmac251 and SIV- mac239) to nonpathogenic (SIVmac1A11) when inoculated intravenously into juvenile and adult rhesus macaques.Sixnewbornmacaquesinoculatedwithpathogenic,unclonedSIVmac251developedpersistent,high levelsofcell-associatedandcell-freeviremia,hadnodetectableantiviralantibodies,andhadpoorweightgain;

  9. Complete Genome Sequence of Viral Hemorrhagic Septicemia Virus Isolated from an Olive Flounder in South Korea

    PubMed Central

    Kim, Jong-Oh; Kim, Wi-Sik; Nishizawa, Toyohiko

    2013-01-01

    Viral hemorrhagic septicemia virus (VHSV) is a seriously problematic pathogen in olive flounder (Paralichthys olivaceus) aquaculture farms in South Korea. Here, we report the complete genome sequence of VHSV which was isolated from spleen and kidney tissues of dead fish at an aquaculture farm in 2005. This genome sequence will be useful for virus diagnostics and in comparative analyses with other virus genotypes. PMID:24009117

  10. Host-pathogen interaction in HIV infection

    PubMed Central

    Chowdhury, Ankita; Silvestri, Guido

    2013-01-01

    The host pathogen interaction is strikingly complex during HIV infection. While several immune effector mechanisms (i.e., cytotoxic T cells, neutralizing antibodies, NK cells, etc) can play a strong antiviral role in vivo, the virus is remarkably able to evade these responses. In addition, the virus preferentially infects and kills activated memory CD4+ T cells, thus exploiting the host antiviral immune response as a source of new cellular targets for infection. Recent advances in understanding (i) how HIV perturbs the host immune system, (ii) how the immune system fights HIV; and (iii) how HIV disease persists when virus replication is suppressed by antiretroviral drugs may hopefully lead to better prevention and treatment strategies for this deadly viral infection. PMID:23890585

  11. Prospects for a novel ultrashort pulsed laser technology for pathogen inactivation

    PubMed Central

    2012-01-01

    The threat of emerging pathogens and microbial drug resistance has spurred tremendous efforts to develop new and more effective antimicrobial strategies. Recently, a novel ultrashort pulsed (USP) laser technology has been developed that enables efficient and chemical-free inactivation of a wide spectrum of viral and bacterial pathogens. Such a technology circumvents the need to introduce potentially toxic chemicals and could permit safe and environmentally friendly pathogen reduction, with a multitude of possible applications including the sterilization of pharmaceuticals and blood products, and the generation of attenuated or inactivated vaccines. PMID:22768792

  12. Pathogen-like particles: biomimetic vaccine carriers engineered at the nanoscale.

    PubMed

    Rosenthal, Joseph A; Chen, Linxiao; Baker, Jenny L; Putnam, David; DeLisa, Matthew P

    2014-08-01

    Vaccine adjuvants are an essential component of vaccine design, helping to generate immunity to pathogen antigens in the absence of infection. Recent advances in nanoscale engineering have created a new class of particulate bionanotechnology that uses biomimicry to better integrate adjuvant and antigen. These pathogen-like particles, or PLPs, can come from a variety of sources, ranging from fully synthetic platforms to biologically derived, self-assembling systems. By employing molecularly engineered targeting and stimulation of key immune cells, recent studies utilizing PLPs as vaccine delivery platforms have shown great promise against high-impact, unsolved vaccine targets ranging from bacterial and viral pathogens to cancer and addiction. PMID:24832075

  13. Emerging viral diseases of fish and shrimp.

    PubMed

    Walker, Peter J; Winton, James R

    2010-01-01

    The rise of aquaculture has been one of the most profound changes in global food production of the past 100 years. Driven by population growth, rising demand for seafood and a levelling of production from capture fisheries, the practice of farming aquatic animals has expanded rapidly to become a major global industry. Aquaculture is now integral to the economies of many countries. It has provided employment and been a major driver of socio-economic development in poor rural and coastal communities, particularly in Asia, and has relieved pressure on the sustainability of the natural harvest from our rivers, lakes and oceans. However, the rapid growth of aquaculture has also been the source of anthropogenic change on a massive scale. Aquatic animals have been displaced from their natural environment, cultured in high density, exposed to environmental stress, provided artificial or unnatural feeds, and a prolific global trade has developed in both live aquatic animals and their products. At the same time, over-exploitation of fisheries and anthropogenic stress on aquatic ecosystems has placed pressure on wild fish populations. Not surprisingly, the consequence has been the emergence and spread of an increasing array of new diseases. This review examines the rise and characteristics of aquaculture, the major viral pathogens of fish and shrimp and their impacts, and the particular characteristics of disease emergence in an aquatic, rather than terrestrial, context. It also considers the potential for future disease emergence in aquatic animals as aquaculture continues to expand and faces the challenges presented by climate change. PMID:20409453

  14. Emerging viral diseases of fish and shrimp

    PubMed Central

    Walker, Peter J.; Winton, James R.

    2010-01-01

    The rise of aquaculture has been one of the most profound changes in global food production of the past 100 years. Driven by population growth, rising demand for seafood and a levelling of production from capture fisheries, the practice of farming aquatic animals has expanded rapidly to become a major global industry. Aquaculture is now integral to the economies of many countries. It has provided employment and been a major driver of socio-economic development in poor rural and coastal communities, particularly in Asia, and has relieved pressure on the sustainability of the natural harvest from our rivers, lakes and oceans. However, the rapid growth of aquaculture has also been the source of anthropogenic change on a massive scale. Aquatic animals have been displaced from their natural environment, cultured in high density, exposed to environmental stress, provided artificial or unnatural feeds, and a prolific global trade has developed in both live aquatic animals and their products. At the same time, over-exploitation of fisheries and anthropogenic stress on aquatic ecosystems has placed pressure on wild fish populations. Not surprisingly, the consequence has been the emergence and spread of an increasing array of new diseases. This review examines the rise and characteristics of aquaculture, the major viral pathogens of fish and shrimp and their impacts, and the particular characteristics of disease emergence in an aquatic, rather than terrestrial, context. It also considers the potential for future disease emergence in aquatic animals as aquaculture continues to expand and faces the challenges presented by climate change. PMID:20409453

  15. Evolution of microbial pathogens.

    PubMed Central

    Morschhäuser, J; Köhler, G; Ziebuhr, W; Blum-Oehler, G; Dobrindt, U; Hacker, J

    2000-01-01

    Various genetic mechanisms including point mutations, genetic rearrangements and lateral gene transfer processes contribute to the evolution of microbes. Long-term processes leading to the development of new species or subspecies are termed macroevolution, and short-term developments, which occur during days or weeks, are considered as microevolution. Both processes, macro- and microevolution need horizontal gene transfer, which is particularly important for the development of pathogenic microorganisms. Plasmids, bacteriophages and so-called pathogenicity islands (PAIs) play a crucial role in the evolution of pathogens. During microevolution, genome variability of pathogenic microbes leads to new phenotypes, which play an important role in the acute development of an infectious disease. Infections due to Staphylococcus epidermidis, Candida albicans and Escherichia coli will be described with special emphasis on processes of microevolution. In contrast, the development of PAIs is a process involved in macroevolution. PAIs are especially important in processes leading to new pathotypes or even species. In this review, particular attention will be given to the fact that the evolution of pathogenic microbes can be considered as a specific example for microbial evolution in general. PMID:10874741

  16. P53-Mediated Rapid Induction of Apoptosis Conveys Resistance to Viral Infection in Drosophila melanogaster

    PubMed Central

    Liu, Bo; Behura, Susanta K.; Clem, Rollie J.; Schneemann, Anette; Becnel, James; Severson, David W.; Zhou, Lei

    2013-01-01

    Arthropod-borne pathogens account for millions of deaths each year. Understanding the genetic mechanisms controlling vector susceptibility to pathogens has profound implications for developing novel strategies for controlling insect-transmitted infectious diseases. The fact that many viruses carry genes that have anti-apoptotic activity has long led to the hypothesis that induction of apoptosis could be a fundamental innate immune response. However, the cellular mechanisms mediating the induction of apoptosis following viral infection remained enigmatic, which has prevented experimental verification of the functional significance of apoptosis in limiting viral infection in insects. In addition, studies with cultured insect cells have shown that there is sometimes a lack of apoptosis, or the pro-apoptotic response happens relatively late, thus casting doubt on the functional significance of apoptosis as an innate immunity. Using in vivo mosquito models and the native route of infection, we found that there is a rapid induction of reaper-like pro-apoptotic genes within a few hours following exposure to DNA or RNA viruses. Recapitulating a similar response in Drosophila, we found that this rapid induction of apoptosis requires the function of P53 and is mediated by a stress–responsive regulatory region upstream of reaper. More importantly, we showed that the rapid induction of apoptosis is responsible for preventing the expression of viral genes and blocking the infection. Genetic changes influencing this rapid induction of reaper-like pro-apoptotic genes led to significant differences in susceptibility to viral infection. PMID:23408884

  17. Characterization of the Viral Microbiome in Patients with Severe Lower Respiratory Tract Infections, Using Metagenomic Sequencing

    PubMed Central

    Lysholm, Fredrik; Wetterbom, Anna; Lindau, Cecilia; Darban, Hamid; Bjerkner, Annelie; Fahlander, Kristina; Lindberg, A. Michael; Persson, Bengt; Allander, Tobias; Andersson, Björn

    2012-01-01

    The human respiratory tract is heavily exposed to microorganisms. Viral respiratory tract pathogens, like RSV, influenza and rhinoviruses cause major morbidity and mortality from respiratory tract disease. Furthermore, as viruses have limited means of transmission, viruses that cause pathogenicity in other tissues may be transmitted through the respiratory tract. It is therefore important to chart the human virome in this compartment. We have studied nasopharyngeal aspirate samples submitted to the Karolinska University Laboratory, Stockholm, Sweden from March 2004 to May 2005 for diagnosis of respiratory tract infections. We have used a metagenomic sequencing strategy to characterize viruses, as this provides the most unbiased view of the samples. Virus enrichment followed by 454 sequencing resulted in totally 703,790 reads and 110,931 of these were found to be of viral origin by using an automated classification pipeline. The snapshot of the respiratory tract virome of these 210 patients revealed 39 species and many more strains of viruses. Most of the viral sequences were classified into one of three major families; Paramyxoviridae, Picornaviridae or Orthomyxoviridae. The study also identified one novel type of Rhinovirus C, and identified a number of previously undescribed viral genetic fragments of unknown origin. PMID:22355331

  18. Characterization of the viral microbiome in patients with severe lower respiratory tract infections, using metagenomic sequencing.

    PubMed

    Lysholm, Fredrik; Wetterbom, Anna; Lindau, Cecilia; Darban, Hamid; Bjerkner, Annelie; Fahlander, Kristina; Lindberg, A Michael; Persson, Bengt; Allander, Tobias; Andersson, Björn

    2012-01-01

    The human respiratory tract is heavily exposed to microorganisms. Viral respiratory tract pathogens, like RSV, influenza and rhinoviruses cause major morbidity and mortality from respiratory tract disease. Furthermore, as viruses have limited means of transmission, viruses that cause pathogenicity in other tissues may be transmitted through the respiratory tract. It is therefore important to chart the human virome in this compartment. We have studied nasopharyngeal aspirate samples submitted to the Karolinska University Laboratory, Stockholm, Sweden from March 2004 to May 2005 for diagnosis of respiratory tract infections. We have used a metagenomic sequencing strategy to characterize viruses, as this provides the most unbiased view of the samples. Virus enrichment followed by 454 sequencing resulted in totally 703,790 reads and 110,931 of these were found to be of viral origin by using an automated classification pipeline. The snapshot of the respiratory tract virome of these 210 patients revealed 39 species and many more strains of viruses. Most of the viral sequences were classified into one of three major families; Paramyxoviridae, Picornaviridae or Orthomyxoviridae. The study also identified one novel type of Rhinovirus C, and identified a number of previously undescribed viral genetic fragments of unknown origin. PMID:22355331

  19. Cellular versus viral microRNAs in host–virus interaction

    PubMed Central

    Ghosh, Zhumur; Mallick, Bibekanand; Chakrabarti, Jayprokas

    2009-01-01

    MicroRNAs (miRNAs) mark a new paradigm of RNA-directed gene expression regulation in a wide spectrum of biological systems. These small non-coding RNAs can contribute to the repertoire of host-pathogen interactions during viral infection. This interplay has important consequences, both for the virus and the host. There have been reported evidences of host-cellular miRNAs modulating the expression of various viral genes, thereby playing a pivotal role in the host–pathogen interaction network. In the hide-and-seek game between the pathogens and the infected host, viruses have evolved highly sophisticated gene-silencing mechanisms to evade host-immune response. Recent reports indicate that virus too encode miRNAs that protect them against cellular antiviral response. Furthermore, they may exploit the cellular miRNA pathway to their own advantage. Nevertheless, our increasing knowledge of the host–virus interaction at the molecular level should lead us toward possible explanations to viral tropism, latency and oncogenesis along with the development of an effective, durable and nontoxic antiviral therapy. Here, we summarize the recent updates on miRNA-induced gene-silencing mechanism, modulating host–virus interactions with a glimpse of the miRNA-based antiviral therapy for near future. PMID:19095692

  20. Neopolyploidy and pathogen resistance

    PubMed Central

    Oswald, Benjamin P; Nuismer, Scott L

    2007-01-01

    Despite the well-documented historical importance of polyploidy, the mechanisms responsible for the establishment and evolutionary success of novel polyploid lineages remain unresolved. One possibility, which has not been previously evaluated theoretically, is that novel polyploid lineages are initially more resistant to pathogens than the diploid progenitor species. Here, we explore this possibility by developing and analysing mathematical models of interactions between newly formed polyploid lineages and their pathogens. We find that for the genetic mechanisms of pathogen resistance with the best empirical support, newly formed polyploid populations of hosts are expected to be more resistant than their diploid progenitors. This effect can be quite strong and, in the case of perennial species with recurrent polyploid formation, may last indefinitely, potentially providing a general explanation for the successful establishment of novel polyploid lineages. PMID:17686733

  1. Drug Sanctuaries, Low Steady State Viral Loads and Viral Blips.

    SciTech Connect

    Perelson, Alan S.,; Callaway, D. (Duncan); Pomerantz, R. J. (Roger J.); Chen, H. Y.; Markowitz, M.; Ho, David D.; Di Mascio, M. (Michele)

    2002-01-01

    Patients on HAART for long periods of time obtain viral loads (VLs) below 50 copies/ml. Ultrasensitive VL assays show that some of these patients obtain a low steady state VL, while others continue to exhibit VL declines to below 5 copies/ml. Low steady states can be explained by two-compartment models that incorporate a drug sanctuary. Interestingly, when patients exhibit continued declines below 50 copies/ml the rate of decline has a half-life of {approx} 6 months, consistent with some estimates of the rate of latent cell decline. Some patients, despite having sustained undetectable VLs show periods of transient viremia (blips). I will present some statistical characterization of the blips observed in a set of 123 patients, suggesting that blips are generated largely by random processes, that blips tend to correspond to periods of a few weeks in which VLs are elevated, and that VL decay from the peak of a blip may have two-phases. Using new results suggesting that the viral burst size, N {approx} 5 x 10{sup 4}, we estimate the number of cells needed to produce a blip.

  2. Estimating viral titres in solutions with low viral loads.

    PubMed

    Brownie, C; Statt, J; Bauman, P; Buczynski, G; Skjolaas, K; Lee, D; Hotta, J; Roth, N J

    2011-07-01

    An important consideration in the manufacture of products derived from animal or human sources is the virus reduction capacity of the manufacturing process as estimated using validated bench-scale models of relevant manufacturing steps. In these studies, manufacturing process intermediates are spiked with virus and processed using the bench-scale model and the resulting viral titres of input and output samples are typically determined using cell-based infectivity assays. In these assays, the Spearman-Kärber (SK) method is commonly used to estimate titres when there is one or more positive observation (i.e., the presence of any viral cytopathic effect). The SK method is most accurate when the proportion of positive observations ranges from <0.1 to >0.9 across dilutions but can be biased otherwise. Maximum likelihood (ML) based on a single-hit Poisson model is an alternative widely used estimation method. We compared SK with ML and found the methods to have similar properties except for situations in which the concentration of virus is low but measurable. In this case, the SK method produces upwardly biased estimates of titres. Based on our results, we recommend the use of either ML or SK at most virus concentrations; however, at low virus concentrations ML is preferred. PMID:21783380

  3. SEROLOGIC SURVEY OF WHITE-TAILED DEER ON ANTICOSTI ISLAND, QUEBEC FOR BOVINE HERPESVIRUS 1, BOVINE VIRAL DIARRHEA, AND PARAINFLUENZA 3

    Microsoft Academic Search

    Leila Sadi; Robert Joyal; Mario St-Georges; Lucie Lamontagne

    In 1985 unusual mortality was observed among the 3- to 4-yr-old white-tailed deer (Odocoileus virginianus) on Anticosti Island, Qu#{233}bec (Canada). A viral pathogen was suspected to be the cause of the deaths. Thus, a serologic survey for bovine herpesvirus 1 (BHV-1), bovine viral diarrhea (BVD) virus and parainfluenza-3 (P1-3) virus was conducted. We examined 396 deer sera from 1985. Results

  4. Live Cell Imaging of Viral Entry

    PubMed Central

    Sun, Eileen; He, Jiang; Zhuang, Xiaowei

    2013-01-01

    Viral entry encompasses the initial steps of infection starting from virion host cell attachment to viral genome release. Given the dynamic interactions between the virus and the host, many questions related to viral entry can be directly addressed by live cell imaging. Recent advances in fluorescent labeling of viral and cellular components, fluorescence microscopy with high sensitivity and spatiotemporal resolution, and image analysis enabled studies of a broad spectrum across many viral entry steps, including virus-receptor interactions, internalization, intracellular transport, genomic release, nuclear transport, and cell-to-cell transmission. Collectively, these live cell imaging studies have not only enriched our understandings of the viral entry mechanisms, but also provided novel insights into basic cellular biology processes. PMID:23395264

  5. Characterization of bovine viral diarrhea viruses

    Microsoft Academic Search

    A. L. Fernelius; L. F. Velicer

    1968-01-01

    Summary Concentrated preparations of bovine viral diarrhea (BVD) virus were partially purified by agar gel column filtration so that many particles of sub-viral size consisting of cell debris and serum were removed. This purification step is an important one in “cleaning-up” viral preparations for electron microscopic observation. Passage of BVD virus through a column of 1.5% agar beads, calibrated with

  6. Viral Advertising: Definitional Review and Synthesis

    Microsoft Academic Search

    Maria Petrescu; Pradeep Korgaonkar

    2011-01-01

    The objectives of this article are threefold. First, it provides an overview of the past published social media research focusing on different aspects of the viral communication, variously termed “electronic word-of-mouth,” “word-of-mouse,” “viral marketing,” and “buzz.” Second, it clarifies and analyzes the concept of viral advertising in social media. Third, it provides a definition to reduce the prevailing ambiguities in

  7. Pathogens use structural mimicry of native host ligands as a mechanism for host receptor engagement.

    PubMed

    Drayman, Nir; Glick, Yair; Ben-nun-shaul, Orly; Zer, Hagit; Zlotnick, Adam; Gerber, Doron; Schueler-Furman, Ora; Oppenheim, Ariella

    2013-07-17

    A pathogen's ability to engage host receptors is a critical determinant of its host range and interspecies transmissibility, key issues for understanding emerging diseases. However, the identification of host receptors, which are also attractive drug targets, remains a major challenge. Our structural bioinformatics studies reveal that both bacterial and viral pathogens have evolved to structurally mimic native host ligands (ligand mimicry), thus enabling engagement of their cognate host receptors. In contrast to the structural homology, amino acid sequence similarity between pathogen molecules and the mimicked host ligands was low. We illustrate the utility of this concept to identify pathogen receptors by delineating receptor tyrosine kinase Axl as a candidate receptor for the polyomavirus SV40. The SV40-Axl interaction was validated, and its participation in the infection process was verified. Our results suggest that ligand mimicry is widespread, and we present a quick tool to screen for pathogen-host receptor interactions. PMID:23870314

  8. Sequencing Needs for Viral Diagnostics

    SciTech Connect

    Gardner, S N; Lam, M; Mulakken, N J; Torres, C L; Smith, J R; Slezak, T

    2004-01-26

    We built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic DNA signatures, which are short sequences that are sufficient to uniquely identify a viral species. We used our existing DNA diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives). We performed simulations, based on existing sequence data, to assess the number of genome sequences of a target species and of close phylogenetic relatives (''near neighbors'') that are required to predict diagnostic signature regions that are conserved among strains of the target species and unique relative to other bacterial and viral species. For DNA viruses such as variola (smallpox), three target genomes provide sufficient guidance for selecting species-wide signatures. Three near neighbor genomes are critical for species specificity. In contrast, most RNA viruses require four target genomes and no near neighbor genomes, since lack of conservation among strains is more limiting than uniqueness. SARS and Ebola Zaire are exceptional, as additional target genomes currently do not improve predictions, but near neighbor sequences are urgently needed. Our results also indicate that double stranded DNA viruses are more conserved among strains than are RNA viruses, since in most cases there was at least one conserved signature candidate for the DNA viruses and zero conserved signature candidates for the RNA viruses.

  9. DISINFECTION OF EMERGING PATHOGENS

    EPA Science Inventory

    There is a growing awareness of the need to control waterborne microbial pathogens. This presentation will concentate on the role of chemical inactivation, using chlorine, chloramines and ozone as a means of controlling bacterial and protozoan species. Information will be present...

  10. Pathogenicity and virulence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many pathogenic microorganisms are host-specific in that they parasitize only one or a few animal species. For example, the cause of equine strangles, Streptococcus equi subspecies equi, is essentially limited to infection of horses. Others—certain Salmonella serotypes, for example—have a broad host...

  11. The pathogenic equine streptococci

    Microsoft Academic Search

    John F. Timoney

    2004-01-01

    Streptococci pathogenic for the horse include S. equi (S. equi subsp. equi), S. zooepidemicus (S. equi subsp. zooepidemicus), S. dysgalactiae subsp. equisimilis and S. pneumoniae capsule Type III. S. equi is a clonal descendent or biovar of an ancestral S. zooepidemicus strain with which it shares greater than 98% DNA homology and therefore expresses many of the same proteins and

  12. PATHOGEN EQUIVALENCY COMMITTEE (PEC)

    EPA Science Inventory

    The U.S. Environmental Protection Agency created the PEC in 1985 to make recommendations to EPA and State managers on the equivalency of unproven sewage sludge disinfection technologies/processes to either a Process to Significantly Reduce Pathogens (PSRP) or a Process to Further...

  13. New Insights into IDO Biology in Bacterial and Viral Infections

    PubMed Central

    Schmidt, Susanne V.; Schultze, Joachim L.

    2014-01-01

    Initially, indoleamine-2,3-dioxygenase (IDO) has been introduced as a bactericidal effector mechanism and has been linked to T-cell immunosuppression and tolerance. In recent years, evidence has been accumulated that IDO also plays an important role during viral infections including HIV, influenza, and hepatitis B and C. Moreover, novel aspects about the role of IDO in bacterial infections and sepsis have been revealed. Here, we review these recent findings highlighting the central role of IDO and tryptophan metabolism in many major human infections. Moreover, we also shed light on issues concerning human-specific and mouse-specific host–pathogen interactions that need to be considered when studying the biology of IDO in the context of infections. PMID:25157255

  14. Roles of bovine viral diarrhea virus envelope glycoproteins in inducing autophagy in MDBK cells.

    PubMed

    Fu, Qiang; Shi, Huijun; Shi, Mengting; Meng, Luping; Bao, Haiyang; Zhang, Guoqi; Ren, Yan; Zhang, Hui; Guo, Fei; Qiao, Jun; Jia, Bin; Wang, Pengyan; Ni, Wei; Sheng, Jinliang; Chen, Chuangfu

    2014-11-01

    Macroautophagy (autophagy) is an evolutionarily conserved control process that maintains cellular homeostasis in eukaryotic cells. Autophagy principally serves an adaptive role to degrade dysfunctional proteins and to clean damaged organelles in response to pathogenic, viral, or microbial infection, nutrient deprivation and endoplasmic reticulum (ER) stress. In previous study, we showed bovine viral diarrhea virus (BVDV) NADL infection induced autophagy and significantly elevated the expression levels of autophagy-related genes, Beclin1 and ATG14, at 12 h post-infection in MDBK cells. However, the specific mechanisms involved in controlling autophagic activity remain unclear. Here, we investigate the effects of BVDV NADL envelope glycoproteins overexpression on inducing autophagy. The results show that viral envelope glycoproteins E(rns) and E2 overexpression mediated by lentivirus increase the formation of autophagosome, the percentage of GFP-LC3 puncta-positive cells and the expression levels of Beclin1 and ATG14. Whereas E1 overexpression doesn't affect autophagic activity. Collectively, these findings suggest that the viral envelope glycoproteins E(rns) and E2 are involved in inducing autophagy, and provide a mechanistic insight into the regulation of autophagy in viral infected cells. PMID:25245007

  15. Hantaviruses in the Americas and Their Role as Emerging Pathogens

    PubMed Central

    Hjelle, Brian; Torres-Pérez, Fernando

    2010-01-01

    The continued emergence and re-emergence of pathogens represent an ongoing, sometimes major, threat to populations. Hantaviruses (family Bunyaviridae) and their associated human diseases were considered to be confined to Eurasia, but the occurrence of an outbreak in 1993–94 in the southwestern United States led to a great increase in their study among virologists worldwide. Well over 40 hantaviral genotypes have been described, the large majority since 1993, and nearly half of them pathogenic for humans. Hantaviruses cause persistent infections in their reservoir hosts, and in the Americas, human disease is manifest as a cardiopulmonary compromise, hantavirus cardiopulmonary syndrome (HCPS), with case-fatality ratios, for the most common viral serotypes, between 30% and 40%. Habitat disturbance and larger-scale ecological disturbances, perhaps including climate change, are among the factors that may have increased the human caseload of HCPS between 1993 and the present. We consider here the features that influence the structure of host population dynamics that may lead to viral outbreaks, as well as the macromolecular determinants of hantaviruses that have been regarded as having potential contribution to pathogenicity. PMID:21994631

  16. Multiplex screening for blood-borne viral, bacterial, and protozoan parasites using an OpenArray platform.

    PubMed

    Grigorenko, Elena; Fisher, Carolyn; Patel, Sunali; Chancey, Caren; Rios, Maria; Nakhasi, Hira L; Duncan, Robert C

    2014-01-01

    The use of nucleic acid tests for detection of pathogens has improved the safety of blood products. However, ongoing pathogen emergence demonstrates a need for development of devices testing for multiple pathogens simultaneously. One approach combines two proven technologies: Taqman chemistry for target identification and quantification and the OpenArray nanofluidic real-time PCR platform for spatial multiplexing of assays. A panel of Taqman assays was developed to detect nine blood-borne pathogens (BBPs): four viral, two bacterial, and three protozoan parasites. The custom BBP OpenArray plate with 18 assays was tested for specificity and analytical sensitivity for nucleic acid from each purified pathogen and with pathogen-spiked human blood and plasma samples. For most targets, the limits of detection (10 to 10,000 copies/mL) were comparable with existing real-time platforms. The testing of the BBP OpenArray with pathogen-spiked coded human plasma or blood samples and negative control specimens demonstrated no false-positive results among the samples tested and correctly identified pathogens with the lowest concentration detected ranging from 10 cells/mL (Trypanosoma cruzi) to 10,000 cells/mL (Escherichia coli). These results represent a proof of concept that indicated the BBP OpenArray platform in combination with Taqman chemistry may provide a multiplex real-time PCR pathogen detection method that points the way for a next-generation platform for infectious disease testing in blood. PMID:24184228

  17. A Child with Acute Encephalopathy Associated with Quadruple Viral Infection

    PubMed Central

    Nakata, Keiko; Kashiwagi, Mitsuru; Masuda, Midori; Shigehara, Seiji; Oba, Chizu; Murata, Shinya; Kase, Tetsuo; Komano, Jun A.

    2015-01-01

    Pediatric acute encephalopathy (AE) was sometimes attributed to virus infection. However, viral infection does not always result in AE. The risk factors for developing infantile AE upon virus infection remain to be determined. Here, we report an infant with AE co-infected with human herpesvirus-6 (HHV-6) and three picornaviruses, including coxsackievirus A6 (CVA6), Enterovirus D68 (EV-D68), and human parechovirus (HPeV). EV-D68 was vertically transmitted to the infant from his mother. CVA6 and HPeV were likely transmitted to the infant at the nursery school. HHV-6 might be re-activated in the patient. It remained undetermined, which pathogen played the central role in the AE pathogenesis. However, active, simultaneous infection of four viruses should have evoked the cytokine storm, leading to the pathogenesis of AE. Conclusion: an infant case with active quadruple infection of potentially AE-causing viruses was seldom reported partly because systematic nucleic acid-based laboratory tests on picornaviruses were not common. We propose that simultaneous viral infection may serve as a risk factor for the development of AE.

  18. Building a viral capsid in the presence of genomic RNA

    NASA Astrophysics Data System (ADS)

    Dykeman, Eric C.; Stockley, Peter G.; Twarock, Reidun

    2013-02-01

    Virus capsid assembly has traditionally been considered as a process that can be described primarily via self-assembly of the capsid proteins, neglecting interactions with other viral or cellular components. Our recent work on several ssRNA viruses, a major class of viral pathogens containing important human, animal, and plant viruses, has shown that this protein-centric view is too simplistic. Capsid assembly for these viruses relies strongly on a number of cooperative roles played by the genomic RNA. This realization requires a new theoretical framework for the modeling and prediction of the assembly behavior of these viruses. In a seminal paper Zlotnick [J. Mol. Biol.0022-283610.1006/jmbi.1994.1473 241, 59 (1994)] laid the foundations for the modeling of capsid assembly as a protein-only self-assembly process, illustrating his approach using the example of a dodecahedral study system. We describe here a generalized framework for modeling assembly that incorporates the regulatory functions provided by cognate protein-nucleic-acid interactions between capsid proteins and segments of the genomic RNA, called packaging signals, into the model. Using the same dodecahedron system we demonstrate, using a Gillespie-type algorithm to deal with the enhanced complexity of the problem instead of a master equation approach, that assembly kinetics and yield strongly depend on the distribution and nature of the packaging signals, highlighting the importance of the crucial roles of the RNA in this process.

  19. Viral warts in organ transplant recipients: new aspects in therapy.

    PubMed

    Schmook, T; Nindl, I; Ulrich, C; Meyer, T; Sterry, W; Stockfleth, E

    2003-11-01

    The long-term success of organ transplantation depends on the prevention of allograft rejection and improvement in quality of life for the patients. This has been achieved through better immunosuppressive regimens with lower dosages and a new generation of immunosuppressive drugs. However, these immunosuppressive agents not only impair the patient's reactivity to the graft, but also to infectious organisms, thereby making them more susceptible to opportunistic pathogens. Because of this, organ transplant recipients are predisposed to epithelial malignancies and infections. The majority of transplant recipients will develop warts induced by human papillomavirus (HPV). Some of these viral warts may present with atypical histological features and may progress into squamous cell carcinomas. The risk for cutaneous cancers after transplantation is much higher than in the immunocompetent population. Current therapies for HPV-associated skin tumours mainly depend on the destruction of affected skin areas. These treatment modalities are of limited efficacy and are usually painful for the patients. A promising novel therapeutic agent is imiquimod, an immune response modifier. Clinical efficacy of imiquimod has been observed for different skin lesions, including viral warts in both immunocompetent and immunosuppressed patients. PMID:14616341

  20. Synthetic DNA vaccine strategies against persistent viral infections

    PubMed Central

    Villarreal, Daniel O; Talbott, Kendra T; Choo, Daniel K; Shedlock, Devon J; Weiner, David B

    2015-01-01

    The human body has developed an elaborate defense system against microbial pathogens and foreign antigens. However, particular microbes have evolved sophisticated mechanisms to evade immune surveillance, allowing persistence within the human host. In an effort to combat such infections, intensive research has focused on the development of effective prophylactic and therapeutic countermeasures to suppress or clear persistent viral infections. To date, popular therapeutic strategies have included the use of live-attenuated microbes, viral vectors and dendritic-cell vaccines aiming to help suppress or clear infection. In recent years, improved DNA vaccines have now re-emerged as a promising candidate for therapeutic intervention due to the development of advanced optimization and delivery technologies. For instance, genetic optimization of synthetic plasmid constructs and their encoded antigens, in vivo electroporation-mediated vaccine delivery, as well as codelivery with molecular adjuvants have collectively enhanced both transgene expression and the elicitation of vaccine-induced immunity. In addition, the development of potent heterologous prime–boost regimens has also provided significant contributions to DNA vaccine immunogenicity. Herein, the authors will focus on these recent improvements to this synthetic platform in relation to their application in combating persistent virus infection. PMID:23659301

  1. Insect Vectors of Human Pathogens

    NSDL National Science Digital Library

    0000-00-00

    Four orders of insects (Hemiptera, Phthiraptera, Diptera, and Siphonaptera) are covered detailing vector species along with their pathogens of human importance. Links to pathogens as well as vectors are highlighted (some of these are CDC, and WHO).

  2. Multiplex detection of agricultural pathogens

    DOEpatents

    Siezak, Thomas R.; Gardner, Shea; Torres, Clinton; Vitalis, Elizabeth; Lenhoff, Raymond J.

    2013-01-15

    Described are kits and methods useful for detection of agricultural pathogens in a sample. Genomic sequence information from agricultural pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay and/or an array assay to successfully identify the presence or absence of pathogens in a sample.

  3. Multiplex detection of agricultural pathogens

    DOEpatents

    McBride, Mary Teresa (Brentwood, CA); Slezak, Thomas Richard (Livermore, CA); Messenger, Sharon Lee (Kensington, CA)

    2010-09-14

    Described are kits and methods useful for detection of seven agricultural pathogens (BPSV; BHV; BVD; FMDV; BTV; SVD; and VESV) in a sample. Genomic sequence information from 7 agricultural pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay to successfully identify the presence or absence of pathogens in a sample.

  4. Viral diagnosis by antigen detection techniques

    Microsoft Academic Search

    Monica Grandien

    1996-01-01

    Background: Diagnosis of viral infections can be obtained in the early stages of a disease by detection of viral antigens directly in the clinical specimen. This has become an important tool for rapid virus diagnosis.Methods: Antigens produced during virus infections can be detected either in cells collected from the site of infection by immunohistological investigation or in secretions and blood

  5. Choosing a Viral Vector System Janet Douglas

    E-print Network

    Chapman, Michael S.

    #12;Retroviral vector design Delete packaging signal Maintain packaging signal #12;The Problem viral vectors are "designed" to infect all cell types...tropism of virus = tropism of vector · Some for AAV (small packaging size) #12;#12;Recombinant Viral Vector Systems · Vector has characteristics

  6. Viral Ancestors of Antiviral Systems

    PubMed Central

    Villarreal, Luis P.

    2011-01-01

    All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the ‘Big Bang’ theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features. PMID:22069523

  7. Viral ancestors of antiviral systems.

    PubMed

    Villarreal, Luis P

    2011-10-01

    All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the 'Big Bang' theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features. PMID:22069523

  8. Pathogenicity Islands in Bacterial Pathogenesis

    PubMed Central

    Schmidt, Herbert; Hensel, Michael

    2004-01-01

    In this review, we focus on a group of mobile genetic elements designated pathogenicity islands (PAI). These elements play a pivotal role in the virulence of bacterial pathogens of humans and are also essential for virulence in pathogens of animals and plants. Characteristic molecular features of PAI of important human pathogens and their role in pathogenesis are described. The availability of a large number of genome sequences of pathogenic bacteria and their benign relatives currently offers a unique opportunity for the identification of novel pathogen-specific genomic islands. However, this knowledge has to be complemented by improved model systems for the analysis of virulence functions of bacterial pathogens. PAI apparently have been acquired during the speciation of pathogens from their nonpathogenic or environmental ancestors. The acquisition of PAI not only is an ancient evolutionary event that led to the appearance of bacterial pathogens on a timescale of millions of years but also may represent a mechanism that contributes to the appearance of new pathogens within a human life span. The acquisition of knowledge about PAI, their structure, their mobility, and the pathogenicity factors they encode not only is helpful in gaining a better understanding of bacterial evolution and interactions of pathogens with eukaryotic host cells but also may have important practical implications such as providing delivery systems for vaccination, tools for cell biology, and tools for the development of new strategies for therapy of bacterial infections. PMID:14726454

  9. Viral origin of antiphospholipid antibodies: endothelial cell activation and thrombus enhancement by CMV peptide-induced APL antibodies.

    PubMed

    Gharavi, Azzudin E; Pierangeli, Silvia S; Harris, E Nigel

    2003-01-01

    Our observations and those from others, give further support to our hypothesis that "autoimmune aPL" may be generated by immunization with products from bacteria or viruses after incidental exposure or infection. We also were able to generate APS-like syndrome in a strain of mice susceptible to autoimmunity, indicating that other factors such as genetics are likely to be involved in the development of APS. Furthermore, not all aPL antibodies generated by immunization with bacterial or viral products are pathogenic. Based on the clinical experience and on the numerous reports indicating presence of aPL in a large number of infectious diseases, it may be expected that not all aPL antibodies produced during infection will be pathogenic. We hypothesize that a limited number aPL antibodies induced by certain viral/bacterial products would be pathogenic in certain groups of predisposed individuals. Identification of these bacterial and/ or viral agents may help to find strategies for the prevention of production of aPL "pathogenic" antibodies. Alternatively, free peptides may be used to induce tolerance against aPL production. PMID:12638901

  10. Comorbidity and high viral load linked to clinical presentation of respiratory human bocavirus infection.

    PubMed

    Ghietto, Lucía María; Majul, Diego; Ferreyra Soaje, Patricia; Baumeister, Elsa; Avaro, Martín; Insfrán, Constanza; Mosca, Liliana; Cámara, Alicia; Moreno, Laura Beatriz; Adamo, Maria Pilar

    2015-01-01

    Human bocavirus (HBoV) is a new parvovirus associated with acute respiratory tract infection (ARTI). In order to evaluate HBoV significance as an agent of acute respiratory disease, we screened 1,135 respiratory samples from children and adults with and without symptoms during two complete calendar years. HBoV1 prevalence in patients with ARTI was 6.33 % in 2011 and 11.64 % in 2012, including neonatal and adult patients. HBoV1 was also detected in 3.77 % of asymptomatic individuals. The co-detection rate was 78.1 %. Among children, 87 % were clinically diagnosed with lower respiratory infection (no significant differences between patients with and without coinfection), and 31 % exhibited comorbidities. Pediatric patients with comorbidities were significantly older than patients without comorbidities. Patients with ARTI had either high or low viral load, while controls had only low viral load, but there were no clinical differences between patients with high or low viral load. In conclusion, we present evidence of the pathogenic potential of HBoV1 in young children with ARTI. Since patients with HBoV1-single infection are not significantly different from those with coinfection with respect to clinical features, the virus can be as pathogenic by itself as other respiratory agents are. Furthermore, an association between high HBoV1 load and disease could not be demonstrated in this study, but all asymptomatic individuals had low viral loads. Also, children with comorbidities are susceptible to HBoV1 infection at older ages than previously healthy children. Thus, the clinical presentation of infection may occur depending on both viral load and the particular interaction between the HBoV1 and the host. PMID:25269520

  11. Chitosan against cutaneous pathogens

    PubMed Central

    2013-01-01

    Propionibacterium acnes and Staphylococcus aureus are cutaneous pathogens that have become increasingly resistant to antibiotics. We sought to determine if chitosan, a polymer of deacetylated chitin, could be used as a potential treatment against these bacteria. We found that higher molecular weight chitosan had superior antimicrobial properties compared to lower molecular weights, and that this activity occurred in a pH dependent manner. Electron and fluorescence microscopy revealed that chitosan forms aggregates and binds to the surface of bacteria, causing shrinkage of the bacterial membrane from the cell wall. Of special relevance, clinical isolates of P. acnes were vulnerable to chitosan, which could be combined with benzoyl peroxide for additive antibacterial effect. Chitosan also demonstrated significantly less cytotoxicity to monocytes than benzoyl peroxide. Overall, chitosan demonstrates many promising qualities for treatment of cutaneous pathogens. PMID:23829873

  12. Adhesion by Pathogenic Corynebacteria

    Microsoft Academic Search

    Elizabeth A. Rogers; Asis Das; Hung Ton-That

    \\u000a Pathogenic members of the genus Corynebacterium cause a wide range of serious infections in humans including diphtheria. Adhesion to host cells is a crucial step during\\u000a infection. In Corynebacterium diphtheriae, adhesion is mediated primarily by filamentous structures called pili or fimbriae that are covalently attached to the bacterial\\u000a cell wall. C. diphtheriae produces three distinct pilus structures, SpaA-, SpaD- and

  13. Selective Serotonin Reuptake Inhibitor Fluoxetine Inhibits Replication of Human Enteroviruses B and D by Targeting Viral Protein 2C

    PubMed Central

    Ulferts, Rachel; van der Linden, Lonneke; Thibaut, Hendrik Jan; Lanke, Kjerstin H. W.; Leyssen, Pieter; Coutard, Bruno; De Palma, Armando M.; Canard, Bruno; Neyts, Johan

    2013-01-01

    Although the genus Enterovirus contains many important human pathogens, there is no licensed drug for either the treatment or the prophylaxis of enterovirus infections. We report that fluoxetine (Prozac)—a selective serotonin reuptake inhibitor—inhibits the replication of human enterovirus B (HEV-B) and HEV-D but does not affect the replication of HEV-A and HEV-C or human rhinovirus A or B. We show that fluoxetine interferes with viral RNA replication, and we identified viral protein 2C as the target of this compound. PMID:23335743

  14. Genome-wide screening using RNAi (RNA interference) to study host factors in viral replication and pathogenesis

    PubMed Central

    Houzet, Laurent; Jeang, Kuan-Teh

    2012-01-01

    With the recent development of siRNA and shRNA expression libraries, RNAi technology has been extensively employed to identify genes involved in diverse cellular processes, such as signal transduction, cell cycle, cancer biology and host-pathogen interactions. In the field of viral infection, this approach has already identified hundreds of new genes not previously known to be important for various virus lifecycles. In this brief review, we focus on recent studies performed using genome-wide RNAi-based screens in mammalian cells for the identification of essential host factors for viral infection and pathogenesis. PMID:21727185

  15. A Natural Genetic Variant of Granzyme B Confers Lethality to a Common Viral Infection

    PubMed Central

    Andoniou, Christopher E.; Sutton, Vivien R.; Wikstrom, Matthew E.; Fleming, Peter; Thia, Kevin Y. T.; Matthews, Antony Y.; Kaiserman, Dion; Schuster, Iona S.; Coudert, Jerome D.; Eldi, Preethi; Chaudhri, Geeta; Karupiah, Gunasegaran; Bird, Phillip I.

    2014-01-01

    Many immune response genes are highly polymorphic, consistent with the selective pressure imposed by pathogens over evolutionary time, and the need to balance infection control with the risk of auto-immunity. Epidemiological and genomic studies have identified many genetic variants that confer susceptibility or resistance to pathogenic micro-organisms. While extensive polymorphism has been reported for the granzyme B (GzmB) gene, its relevance to pathogen immunity is unexplored. Here, we describe the biochemical and cytotoxic functions of a common allele of GzmB (GzmBW) common in wild mouse. While retaining ‘Asp-ase’ activity, GzmBW has substrate preferences that differ considerably from GzmBP, which is common to all inbred strains. In vitro, GzmBW preferentially cleaves recombinant Bid, whereas GzmBP activates pro-caspases directly. Recombinant GzmBW and GzmBP induced equivalent apoptosis of uninfected targets cells when delivered with perforin in vitro. Nonetheless, mice homozygous for GzmBW were unable to control murine cytomegalovirus (MCMV) infection, and succumbed as a result of excessive liver damage. Although similar numbers of anti-viral CD8 T cells were generated in both mouse strains, GzmBW-expressing CD8 T cells isolated from infected mice were unable to kill MCMV-infected targets in vitro. Our results suggest that known virally-encoded inhibitors of the intrinsic (mitochondrial) apoptotic pathway account for the increased susceptibility of GzmBW mice to MCMV. We conclude that different natural variants of GzmB have a profound impact on the immune response to a common and authentic viral pathogen. PMID:25502180

  16. Human coronaviruses: viral and cellular factors involved in neuroinvasiveness and neuropathogenesis.

    PubMed

    Desforges, Marc; Le Coupanec, Alain; Stodola, Jenny K; Meessen-Pinard, Mathieu; Talbot, Pierre J

    2014-12-19

    Among the various respiratory viruses infecting human beings, coronaviruses are important pathogens, which usually infect the upper respiratory tract, where they are mainly associated with common colds. However, in more vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, leading to pneumonia, exacerbations of asthma, and various types of respiratory distress syndrome. The respiratory involvement of human coronaviruses has been clearly established since the 1960s. Nevertheless, for almost three decades now, data reported in the scientific literature has also demonstrated that, like it was described for other human viruses, coronaviruses have neuroinvasive capacities since they can spread from the respiratory tract to the central nervous system (CNS). Once there, infection of CNS cells (neurotropism) could lead to human health problems, such as encephalitis and long-term neurological diseases. Neuroinvasive coronaviruses could damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuroimmunopathology) and/or viral replication, which directly induces damage to CNS cells (virus-induced neuropathology). Given all these properties, it has been suggested that these opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of neurologic diseases for which the etiology remains poorly understood. Herein, we present host and viral factors that participate in the regulation of the possible pathogenic processes associated with CNS infection by human coronaviruses and we try to decipher the intricate interplay between virus and host target cells in order to characterize their role in the virus life cycle as well as in the capacity of the cell to respond to viral invasion. PMID:25281913

  17. Viral Infection of the Lungs through the Eye?

    PubMed Central

    Bitko, Vira; Musiyenko, Alla; Barik, Sailen

    2007-01-01

    Respiratory syncytial virus (RSV) is the foremost respiratory pathogen in newborns and claims millions of lives annually. However, there has been no methodical study of the pathway(s) of entry of RSV or its interaction with nonrespiratory tissues. We and others have recently established a significant association between allergic conjunctivitis and the presence of RSV in the eye. Here we adopt a BALB/c mouse model and demonstrate that when instilled in the live murine eye, RSV not only replicated robustly in the eye but also migrated to the lung and produced a respiratory disease that is indistinguishable from the standard, nasally acquired RSV disease. Ocularly applied synthetic anti-RSV small interfering RNA prevented infection of the eye as well as the lung. RSV infection of the eye activated a plethora of ocular cytokines and chemokines with profound relevance to inflammation of the eye. Anticytokine treatments in the eye reduced ocular inflammation but had no effect on viral growth in both eye and lung, demonstrating a role of the cytokine response in ocular pathology. These results establish the eye as a major gateway of respiratory infection and a respiratory virus as a bona fide eye pathogen, thus offering novel intervention and treatment options. PMID:17050596

  18. PIPS: Pathogenicity Island Prediction Software

    PubMed Central

    Soares, Siomar C.; Abreu, Vinícius A. C.; Ramos, Rommel T. J.; Cerdeira, Louise; Silva, Artur; Baumbach, Jan; Trost, Eva; Tauch, Andreas; Hirata, Raphael; Mattos-Guaraldi, Ana L.; Miyoshi, Anderson; Azevedo, Vasco

    2012-01-01

    The adaptability of pathogenic bacteria to hosts is influenced by the genomic plasticity of the bacteria, which can be increased by such mechanisms as horizontal gene transfer. Pathogenicity islands play a major role in this type of gene transfer because they are large, horizontally acquired regions that harbor clusters of virulence genes that mediate the adhesion, colonization, invasion, immune system evasion, and toxigenic properties of the acceptor organism. Currently, pathogenicity islands are mainly identified in silico based on various characteristic features: (1) deviations in codon usage, G+C content or dinucleotide frequency and (2) insertion sequences and/or tRNA genetic flanking regions together with transposase coding genes. Several computational techniques for identifying pathogenicity islands exist. However, most of these techniques are only directed at the detection of horizontally transferred genes and/or the absence of certain genomic regions of the pathogenic bacterium in closely related non-pathogenic species. Here, we present a novel software suite designed for the prediction of pathogenicity islands (pathogenicity island prediction software, or PIPS). In contrast to other existing tools, our approach is capable of utilizing multiple features for pathogenicity island detection in an integrative manner. We show that PIPS provides better accuracy than other available software packages. As an example, we used PIPS to study the veterinary pathogen Corynebacterium pseudotuberculosis, in which we identified seven putative pathogenicity islands. PMID:22355329

  19. Exosomes and other extracellular vesicles in host-pathogen interactions.

    PubMed

    Schorey, Jeffrey S; Cheng, Yong; Singh, Prachi P; Smith, Victoria L

    2015-01-01

    An effective immune response requires the engagement of host receptors by pathogen-derived molecules and the stimulation of an appropriate cellular response. Therefore, a crucial factor in our ability to control an infection is the accessibility of our immune cells to the foreign material. Exosomes-which are extracellular vesicles that function in intercellular communication-may play a key role in the dissemination of pathogen- as well as host-derived molecules during infection. In this review, we highlight the composition and function of exosomes and other extracellular vesicles produced during viral, parasitic, fungal and bacterial infections and describe how these vesicles could function to either promote or inhibit host immunity. PMID:25488940

  20. Human pathogenic bacteria, fungi, and viruses in Drosophila

    PubMed Central

    Panayidou, Stavria; Ioannidou, Eleni; Apidianakis, Yiorgos

    2014-01-01

    Drosophila has been the invertebrate model organism of choice for the study of innate immune responses during the past few decades. Many Drosophila–microbe interaction studies have helped to define innate immunity pathways, and significant effort has been made lately to decipher mechanisms of microbial pathogenesis. Here we catalog 68 bacterial, fungal, and viral species studied in flies, 43 of which are relevant to human health. We discuss studies of human pathogens in flies revealing not only the elicitation and avoidance of immune response but also mechanisms of tolerance, host tissue homeostasis, regeneration, and predisposition to cancer. Prominent among those is the emerging pattern of intestinal regeneration as a defense response induced by pathogenic and innocuous bacteria. Immunopathology mechanisms and many microbial virulence factors have been elucidated, but their relevance to human health conventionally necessitates validation in mammalian models of infection. PMID:24398387

  1. A microfluidic system integrated with buried optical fibers for detection of Phalaenopsis orchid pathogens.

    PubMed

    Lin, Chih-Lin; Chang, Wen-Hsin; Wang, Chih-Hung; Lee, Chia-Hwa; Chen, Tzong-Yueh; Jan, Fuh-Jyh; Lee, Gwo-Bin

    2015-01-15

    Orchids of the genus Phalaenopsis are some of the most economically important plants in Taiwan. Fast, accurate, and on-site detection of pathogens in these orchids is therefore of critical importance in order to prevent or suppress costly disease outbreaks. Traditional pathogen detection methods are time-consuming, require well-equipped laboratories with highly trained personnel, and cannot be conducted in situ. In this study, a microfluidic system integrated with buried optical fibers was developed to detect viral pathogens of Phalaenopsis spp. Briefly, virus-specific ribonucleic acid (RNA) purification was achieved by a pre-treatment incubation with magnetic beads, and reverse-transcription loop-mediated isothermal amplification (RT-LAMP) was used subsequently to amplify the viral RNA. Positive RT-LAMP reactions resulted in the precipitation of magnesium pyrophosphate, which caused a change in turbidity that could be seen by the naked eye. A buried optical fiber-based detection module and a micro-stirring device were then integrated into the microfluidic chip to detect the RT-LAMP reaction product directly on the chip itself by measuring the change in the optical signals caused by the turbidity change associated with a positive amplification. The limit of detection for this system was found to be 25 fg, which is of similar sensitivity to existing, more laborious methods. Therefore, by using the integrated microfluidic system, a sensitive, rapid, accurate, and automatic diagnosis of viral pathogens in Phalaenopsis spp. orchids could be achieved within only 65 min. PMID:25168766

  2. Dynamic models of viral replication and latency

    PubMed Central

    Mohammadi, Pejman; Ciuffi, Angela; Beerenwinkel, Niko

    2015-01-01

    Purpose of review HIV targets primary CD4+ T cells. The virus depends on the physiological state of its target cells for efficient replication, and, in turn, viral infection perturbs the cellular state significantly. Identifying the virus–host interactions that drive these dynamic changes is important for a better understanding of viral pathogenesis and persistence. The present review focuses on experimental and computational approaches to study the dynamics of viral replication and latency. Recent findings It was recently shown that only a fraction of the inducible latently infected reservoirs are successfully induced upon stimulation in ex-vivo models while additional rounds of stimulation make allowance for reactivation of more latently infected cells. This highlights the potential role of treatment duration and timing as important factors for successful reactivation of latently infected cells. The dynamics of HIV productive infection and latency have been investigated using transcriptome and proteome data. The cellular activation state has shown to be a major determinant of viral reactivation success. Mathematical models of latency have been used to explore the dynamics of the latent viral reservoir decay. Summary Timing is an important component of biological interactions. Temporal analyses covering aspects of viral life cycle are essential for gathering a comprehensive picture of HIV interaction with the host cell and untangling the complexity of latency. Understanding the dynamic changes tipping the balance between success and failure of HIV particle production might be key to eradicate the viral reservoir. PMID:25565177

  3. A Novel Host-Proteome Signature for Distinguishing between Acute Bacterial and Viral Infections

    PubMed Central

    Oved, Kfir; Cohen, Asi; Boico, Olga; Navon, Roy; Friedman, Tom; Etshtein, Liat; Kriger, Or; Bamberger, Ellen; Fonar, Yura; Yacobov, Renata; Wolchinsky, Ron; Denkberg, Galit; Dotan, Yaniv; Hochberg, Amit; Reiter, Yoram; Grupper, Moti; Srugo, Isaac; Feigin, Paul; Gorfine, Malka; Chistyakov, Irina; Dagan, Ron; Klein, Adi; Potasman, Israel; Eden, Eran

    2015-01-01

    Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P<0.001), as well as routinely used clinical parameters and their combinations (P<0.001). It remained robust across different physiological systems, times from symptom onset, and pathogens (AUCs 0.87-1.0). The accurate differential diagnosis provided by this novel combination of viral- and bacterial-induced proteins has the potential to improve management of patients with acute infections and reduce antibiotic misuse. PMID:25785720

  4. Identification of novel viral receptors with cell line expressing viral receptor-binding protein

    PubMed Central

    Mei, Mei; Ye, Jianqiang; Qin, Aijian; Wang, Lin; Hu, Xuming; Qian, Kun; Shao, Hongxia

    2015-01-01

    The viral cell receptors and infection can be blocked by the expression of the viral receptor-binding protein. Thus, the viral cell receptor is an attractive target for anti-viral strategies, and the identification of viral cell receptor is critical for better understanding and controlling viral disease. As a model system for viral entry and anti-retroviral approaches, avian sarcoma/leukosis virus (ASLV, including the A-J ten subgroups) has been studied intensively and many milestone discoveries have been achieved based on work with ASLV. Here, we used a DF1 cell line expressed viral receptor-binding protein to efficiently identify chicken Annexin A2 (chANXA2) as a novel receptor for retrovirus ALV-J (avian leukosis virus subgroup J). Our data demonstrate that antibodies or siRNA to chANXA2 significantly inhibited ALV-J infection and replication, and over-expression of chANXA2 permitted the entry of ALV-J into its non-permissible cells. Our findings have not only identified chANXA2 as a novel biomarker for anti-ALV-J, but also demonstrated that cell lines with the expression of viral receptor-binding protein could be as efficient tools for isolating functional receptors to identify novel anti-viral targets. PMID:25604889

  5. Aptamer-Based Therapeutics: New Approaches to Combat Human Viral Diseases

    PubMed Central

    Shum, Ka-To; Zhou, Jiehua; Rossi, John J.

    2013-01-01

    Viruses replicate inside the cells of an organism and continuously evolve to contend with an ever-changing environment. Many life-threatening diseases, such as AIDS, SARS, hepatitis and some cancers, are caused by viruses. Because viruses have small genome sizes and high mutability, there is currently a lack of and an urgent need for effective treatment for many viral pathogens. One approach that has recently received much attention is aptamer-based therapeutics. Aptamer technology has high target specificity and versatility, i.e., any viral proteins could potentially be targeted. Consequently, new aptamer-based therapeutics have the potential to lead a revolution in the development of anti-infective drugs. Additionally, aptamers can potentially bind any targets and any pathogen that is theoretically amenable to rapid targeting, making aptamers invaluable tools for treating a wide range of diseases. This review will provide a broad, comprehensive overview of viral therapies that use aptamers. The aptamer selection process will be described, followed by an explanation of the potential for treating virus infection by aptamers. Recent progress and prospective use of aptamers against a large variety of human viruses, such as HIV-1, HCV, HBV, SCoV, Rabies virus, HPV, HSV and influenza virus, with particular focus on clinical development of aptamers will also be described. Finally, we will discuss the challenges of advancing antiviral aptamer therapeutics and prospects for future success. PMID:24287493

  6. Storage of cellular 5? mRNA caps in P bodies for viral cap-snatching

    PubMed Central

    Mir, M. A.; Duran, W. A.; Hjelle, B. L.; Ye, C.; Panganiban, A. T.

    2008-01-01

    The minus strand and ambisense segmented RNA viruses include multiple important human pathogens and are divided into three families, the Orthomyxoviridae, the Bunyaviridae, and the Arenaviridae. These viruses all initiate viral transcription through the process of “cap-snatching,” which involves the acquisition of capped 5? oligonucleotides from cellular mRNA. Hantaviruses are emerging pathogenic viruses of the Bunyaviridae family that replicate in the cytoplasm of infected cells. Cellular mRNAs can be actively translated in polysomes or physically sequestered in cytoplasmic processing bodies (P bodies) where they are degraded or stored for subsequent translation. Here we show that the hantavirus nucleocapsid protein binds with high affinity to the 5? cap of cellular mRNAs, protecting the 5? cap from degradation. We also show that the hantavirus nucleocapsid protein accumulates in P bodies, where it sequesters protected 5? caps. P bodies then serve as a pool of primers during the initiation of viral mRNA synthesis by the viral polymerase. We propose that minus strand segmented viruses replicating in the cytoplasm have co-opted the normal degradation machinery of P bodies for storage of cellular caps. Our data also indicate that modification of the cap-snatching model is warranted to include a role for the nucleocapsid protein in cap acquisition and storage. PMID:19047634

  7. Analysis of viral microRNA expression by elephant endotheliotropic herpesvirus 1.

    PubMed

    Furuse, Yuki; Dastjerdi, Akbar; Seilern-Moy, Katharina; Steinbach, Falko; Cullen, Bryan R

    2014-04-01

    Elephant endotheliotropic herpesvirus 1 (EEHV1), a member of the Betaherpesvirinae subfamily, has recently emerged as an important viral pathogen of Asian elephants that can cause a severe, often fatal, hemorrhagic disease. EEHV1 does not replicate in culture and little is currently known about the molecular biology of this emerging pathogen, with the notable exception of its genomic DNA sequence. Here, we have used small RNA deep sequencing to determine whether EEHV1, like other human and murine betaherpesviruses, expresses viral microRNAs in infected tissues in vivo. Our data provide evidence supporting the existence of at least three novel viral microRNAs encoded by EEHV1 and one of these, miR-E3-5p, is shown to repress target mRNA expression. Moreover, miR-E3-5p expression was readily detectable in tissue samples derived from two infected elephants, including in whole blood. These data shed new light on the biology of EEHV1 and identify small RNAs that have the potential to be useful in the diagnosis of sub-clinical infections in captive Asian and African elephants. PMID:24725936

  8. Viral proteins function as ion channels.

    PubMed

    Wang, Kai; Xie, Shiqi; Sun, Bing

    2011-02-01

    Viral ion channels are short membrane proteins with 50-120 amino acids and play an important role either in regulating virus replication, such as virus entry, assembly and release or modulating the electrochemical balance in the subcellular compartments of host cells. This review summarizes the recent advances in viral encoded ion channel proteins (or viroporins), including PBCV-1 KcV, influenza M2, HIV-1 Vpu, HCV p7, picornavirus 2B, and coronavirus E and 3a. We focus on their function and mechanisms, and also discuss viral ion channel protein serving as a potential drug target. PMID:20478263

  9. Health Care–Acquired Viral Respiratory Diseases

    PubMed Central

    Goins, William P.; Talbot, H. Keipp; Talbot, Thomas R.

    2014-01-01

    Health care–associated viral respiratory infections, common among hospitalized children, also occur among adults and institutionalized persons and result in increased patient morbidity, mortality, and health care costs. Approximately 20% of patients with health care–associated pneumonia have viral respiratory infections, with 70% of these infections caused by adenovirus, influenza virus, parainfluenza virus, and respiratory syncytial virus (RSV).1 These infections typically reflect the level of viral activity within the community.1,2 This article focuses on the epidemiology, transmission, and control of health care–associated RSV and influenza virus. PMID:21316002

  10. Simultaneous detection of antibodies to five simian viruses in nonhuman primates using recombinant viral protein based multiplex microbead immunoassays.

    PubMed

    Liao, Qi; Guo, Huishan; Tang, Min; Touzjian, Neal; Lerche, Nicholas W; Lu, Yichen; Yee, JoAnn L

    2011-12-01

    Routine screening for infectious agents is critical in establishing and maintaining specific pathogen free (SPF) nonhuman primate (NHP) colonies. More efficient, higher throughput, less costly reagent, and reduced sample consumption multiplex microbead immunoassays (MMIAs) using purified viral lysates have been developed previously to address some disadvantages of the traditional individual enzyme-linked immunosorbent assay (ELISA) methods. To overcome some of the technical and biosafety difficulties in preparing antigens from live viruses for viral lysate protein based MMIAs, novel MMIAs using recombinant glycoprotein D precursor (gD) protein of herpesvirus B and four viral gag proteins of simian immunodeficiency virus (SIV), simian T Cell lymphotropic virus (STLV), simian foamy virus (SFV), and simian betaretrovirus (SRV) as antigens have been developed in the current study. The data showed that the recombinant viral protein based MMIAs detected simultaneously antibodies to each of these five viruses with high sensitivity and specificity, and correlated well with viral lysate based MMIAs. Therefore, recombinant viral protein based MMIA is an effective and efficient routine screening method to determine the infection status of nonhuman primates. PMID:21945221

  11. Portable pathogen detection system

    DOEpatents

    Milanovich, Fred P.; Brown, Steve B.; Colston, Billy W.; Everett, Matthew; Vendateswaran, Kodumudi; Simon, Jonathan N.

    2005-06-14

    A portable pathogen detection system that accomplishes on-site multiplex detection of targets in biological samples. The system includes: microbead specific reagents, incubation/mixing chambers, a disposable microbead capture substrate, and an optical measurement and decoding arrangement. The basis of this system is a highly flexible Liquid Array that utilizes optically encoded microbeads as the templates for biological assays. Target biological samples are optically labeled and captured on the microbeads, which are in turn captured on an ordered array or disordered array disposable capture substrate and then optically read.

  12. BK polyomavirus: emerging pathogen

    PubMed Central

    Bennett, Shauna M.; Broekema, Nicole M.; Imperiale, Michael J.

    2013-01-01

    BK polyomavirus (BKPyV) is a small double-stranded DNA virus that is an emerging pathogen in immunocompromised individuals. BKPyV is widespread in the general population, but primarily causes disease when immune suppression leads to reactivation of latent virus. Polyomavirus-associated nephropathy and hemorrhagic cystitis in renal and bone marrow transplant patients, respectively, are the most common diseases associated with BKPyV reactivation and lytic infection. In this review, we discuss the clinical relevance, effects on the host, virus life cycle, and current treatment protocols. PMID:22402031

  13. Role of gut pathogens in development of irritable bowel syndrome

    PubMed Central

    Grover, Madhusudan

    2014-01-01

    Acute infectious gastroenteritis is one of the most commonly identifiable risk factors for the development of irritable bowel syndrome (IBS). A number of bacterial, viral and parasitic pathogens have been found to be associated with the development of IBS and other functional gastrointestinal (GI) disorders. Epidemiological studies have identified demographic and acute enteritis-related risk factors for the development of post-infectious-IBS (PI-IBS). Immune dysregulation, alterations in barrier function, serotonergic and mast cell activation have been identified as potential pathophysiological mechanisms. Additionally, variations in host genes involved in barrier function, antigen presentation and cytokine response have been associated with PI-IBS development. However, it is unknown whether specific pathogens have unique effects on long-term alterations in gut physiology or different pathogens converge to cause common alterations resulting in similar phenotype. The role of microbial virulence and pathogenicity factors in development of PI-IBS is also largely unknown. Additionally, alterations in host gut sensation, motility, secretion, and barrier function in PI-IBS need to be elucidated. Finally, both GI infections and antibiotics used to treat these infections can cause long-term alterations in host commensal microbiota. It is plausible that alteration in the commensal microbiome persists in a subset of patients predisposing them to develop PI-IBS. PMID:24604037

  14. MODELING HOST-PATHOGEN INTERACTIONS: COMPUTATIONAL BIOLOGY AND BIOINFORMATICS FOR INFECTIOUS DISEASE RESEARCH (Session introduction)

    SciTech Connect

    McDermott, Jason E.; Braun, Pascal; Bonneau, Richard A.; Hyduke, Daniel R.

    2011-12-01

    Pathogenic infections are a major cause of both human disease and loss of crop yields and animal stocks and thus cause immense damage to the worldwide economy. The significance of infectious diseases is expected to increase in an ever more connected warming world, in which new viral, bacterial and fungal pathogens can find novel hosts and ecologic niches. At the same time, the complex and sophisticated mechanisms by which diverse pathogenic agents evade defense mechanisms and subvert their hosts networks to suit their lifestyle needs is still very incompletely understood especially from a systems perspective [1]. Thus, understanding host-pathogen interactions is both an important and a scientifically fascinating topic. Recently, technology has offered the opportunity to investigate host-pathogen interactions on a level of detail and scope that offers immense computational and analytical possibilities. Genome sequencing was pioneered on some of these pathogens, and the number of strains and variants of pathogens sequenced to date vastly outnumbers the number of host genomes available. At the same time, for both plant and human hosts more and more data on population level genomic variation becomes available and offers a rich field for analysis into the genetic interactions between host and pathogen.

  15. Comparison of fecal indicators with pathogenic bacteria and rotavirus in groundwater

    PubMed Central

    Ferguson, Andrew S.; Layton, Alice C.; Mailloux, Brian J; Culligan, Patricia J.; Williams, Daniel E.; Smartt, Abby E.; Sayler, Gary S.; Feighery, John; McKay, Larry; Knappett, Peter S.K.; Alexandrova, Ekaterina; Arbit, Talia; Emch, Michael; Escamilla, Veronica; Ahmed, Kazi Matin; Alam, Md. Jahangir; Streatfield, P. Kim; Yunus, Mohammad; van Geen, Alexander

    2012-01-01

    Groundwater is routinely analyzed for fecal indicators but direct comparisons of fecal indicators to the presence of bacterial and viral pathogens are rare. This study was conducted in rural Bangladesh where the human population density is high, sanitation is poor, and groundwater pumped from shallow tubewells is often contaminated with fecal bacteria. Five indicator microorganisms (E. coli, total coliform, F+RNA coliphage, Bacteroides and human-associated Bacteroides) and various environmental parameters were compared to the direct detection of waterborne pathogens by quantitative PCR in groundwater pumped from 50 tubewells. Rotavirus was detected in groundwater filtrate from the largest proportion of tubewells (40%), followed by Shigella (10%), Vibrio (10%), and pathogenic E. coli (8%). Spearman rank correlations and sensitivity-specificity calculations indicate that some, but not all, combinations of indicators and environmental parameters can predict the presence of pathogens. Culture-dependent fecal indicator bacteria measured on a single date did not predict total bacterial pathogens, but annually averaged monthly measurements of culturable E. coli did improve prediction for total bacterial pathogens. A qPCR-based E. coli assay was the best indicator for the bacterial pathogens. F+RNA coliphage were neither correlated nor sufficiently sensitive towards rotavirus, but were predictive of bacterial pathogens. Since groundwater cannot be excluded as a significant source of diarrheal disease in Bangladesh and neighboring countries with similar characteristics, the need to develop more effective methods for screening tubewells with respect to microbial contamination is necessary. PMID:22705866

  16. Primary hemocyte culture of Penaeus monodon as an in vitro model for white spot syndrome virus titration, viral and immune related gene expression and cytotoxicity assays

    Microsoft Academic Search

    Seena Jose; A. Mohandas; Rosamma Philip; I. S. Bright Singh

    2010-01-01

    Immortal cell lines have not yet been reported from Penaeus monodon, which delimits the prospects of investigating the associated viral pathogens especially white spot syndrome virus (WSSV). In this context, a method of developing primary hemocyte culture from this crustacean has been standardized by employing modified double strength Leibovitz-15 (L-15) growth medium supplemented with 2% glucose, MEM vitamins (1×), tryptose

  17. Role for Bovine Viral Diarrhea Virus Erns Glycoprotein in the Control of Activation of Beta Interferon by Double-Stranded RNA

    Microsoft Academic Search

    Munir Iqbal; Emma Poole; Stephen Goodbourn; John W. McCauley

    2004-01-01

    Bovine viral diarrhea virus (BVDV) is a Pestivirus belonging to the family Flaviviridae and is a major pathogen of cattle throughout the world with an incidence of infection often in excess of 70% (9, 24). An unusual feature of pestiviruses is their ability to sustain a persistent infection after in utero infection of a fetus. BVDV exists as two biotypes

  18. Mutations induced in the NS5B gene of bovine viral diarrhea virus by antiviral treatment convey resistance to the compound

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) is a widespread bovine pathogen for which there is no specific therapeutic agent. A previous study using 2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772) to treat calves persistently infected with BVDV resulted in a decrease in the vira...

  19. Type I Interferon Reaction to Viral Infection in Interferon-Competent, Immortalized Cell Lines from the African Fruit Bat Eidolon helvum

    Microsoft Academic Search

    Susanne E. Biesold; Daniel Ritz; Florian Gloza-Rausch; Robert Wollny; Jan Felix Drexler; Victor M. Corman; Elisabeth K. V. Kalko; Samuel Oppong; Christian Drosten; Marcel A. Müller

    2011-01-01

    Bats harbor several highly pathogenic zoonotic viruses including Rabies, Marburg, and henipaviruses, without overt clinical symptoms in the animals. It has been suspected that bats might have evolved particularly effective mechanisms to suppress viral replication. Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E.

  20. Accurate detection and quantification of the fish viral hemorrhagic septicemia virus (VHSv) with a two-color fluorometric real-time PCR assay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Viral Hemorrhagic Septicemia virus (VHSv) is one of the world's most serious fish pathogens, infecting > 80 marine, freshwater, and estuarine fish species from Eurasia and North America. A novel and especially virulent strain - IVb - appeared in the Great Lakes in 2003, killed many game fish species...

  1. Replication of H5N1 avian influenza viruses in chickens is affected by the PB1, PB2 and NP viral genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Devastating losses to the poultry industry can result from pathogenic avian influenza viruses (AIVs) created by natural reassortment events. The role of individual viral genes on the pathogenesis of AIVs in chickens is unclear. Reverse genetics was used to create single-gene reassortants to determ...

  2. DEVELOPMENT OF SSRS AND CONVERSION OF RFLP MARKERS TO PCR-BASED MARKERS FOR INTROGRESSION OF VIRAL RESISTANCE GENES FROM SOLANUM ETUBEROSUM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Potato virus X (PVX), potato virus Y (PVY) and potato leafroll virus (PLRV) are important viral pathogens of potato. Solanum etuberosum, a wild relative of potato, is a source of resistance to these viruses that has yet to be fully exploited by plant breeders. A 1 EBN species, S. etuberosum cannot ...

  3. Pathogen-induced reversal of native dominance in a grassland community

    PubMed Central

    Borer, Elizabeth T.; Hosseini, Parviez R.; Seabloom, Eric W.; Dobson, Andrew P.

    2007-01-01

    Disease may play a critical role in invasions by nonnative plants and animals that currently threaten global biodiversity. For example, a generalist viral pathogen has been recently implicated in one of the most extensive plant invasions worldwide, the invasion and domination of California's perennial grasslands by exotic annual grasses. To date, disease has never been quantitatively assessed as a cause of this invasion. Using a model with field-estimated parameters, we demonstrate that pathogen presence was necessary to reverse competitive outcome and to allow exotic annual grass invasion and dominance. Although pathogen-induced reversal of a competitive hierarchy has been suggested as a mechanism of species invasion, here we quantitatively demonstrate the importance of this phenomenon by using field-derived parameters in a dynamical model. Pathogen-mediated reversals in competitive balance may be critically important for understanding past, and predicting future, invasions. PMID:17372211

  4. Identification and origin of plant pathogenic microorganisms in recirculating nutrient solutions.

    PubMed

    Stanghellini, M E; Rasmussen, S L

    1994-11-01

    Avoidance of root-infecting microorganisms was originally considered one of the advantages of cultivation of crops in a soilless, recirculating nutrient solution. However, to date, four viral, three bacterial and 21 fungal pathogens have been identified as causal agents of root disease in hydroponically-grown crops. Root-infecting fungi, particularly those which produce a motile stage known as a zoospore, have been the primary pathogens associated with extensive crop losses. Documented sources of these root pathogens in hydroponic systems include peat, surface water such as rivers and streams, and insects. The severity of disease caused by these introduced root pathogens is primarily governed by the genetic susceptibility of each crop and the temperature of the recirculating nutrient solution. PMID:11540205

  5. Viral Hepatitis: A through E and Beyond

    MedlinePLUS

    ... through E and Beyond | Share External Link Disclaimer Liver Disease Viral Hepatitis: A through E and Beyond Alternate Versions ? PDF Version? (139 KB) Additional Links ? Autoimmune Hepatitis Hepatitis A Hepatitis B Hepatitis C Contact Us Digestive Disease Information Phone: ...

  6. Viral miRNAs and immune evasion

    PubMed Central

    Boss, Isaac W.; Renne, Rolf

    2013-01-01

    Viral miRNAs, ?22nt RNA molecules which post-transcriptionally regulate gene expression, are emerging as important tools in immune evasion. Viral infection is a complex process that requires immune evasion in order to establish persistent life-long infection of the host. During this process viruses express both protein-coding and non-coding genes, which help to modulate the cellular environment making it more favorable for infection. In the last decade, it was uncovered that DNA viruses express a diverse and abundant pool of small non-coding RNA molecules, called microRNAs (miRNAs). These virally encoded miRNAs are non-immunogenic and therefore are important tools used to evade both innate and adaptive immune responses. This review aims to summarize our current knowledge of herpesvirus- and polyomavirus-encoded miRNAs, and how they contribute to immune evasion by targeting viral and/or host cellular genes. PMID:21757042

  7. VIROLOGY: Sensing Viral RNA Amid Your Own

    NSDL National Science Digital Library

    Takashi Fujita (Kyoto University; Institute for Virus Research,)

    2006-11-10

    Access to the article is free, however registration and sign-in are required: Viral RNA has a structural modification that cells recognize. This modification could be used in antiviral therapies and to modulate the immune system.

  8. Surveillance for Viral Hepatitis - United States, 2012

    MedlinePLUS

    ... Page Share Compartir Surveillance for Viral Hepatitis – United States, 2012 Entire report in a printable format [PDF - ... 1 Reported cases of acute hepatitis A, by state ? United States, 2008–2012 Table 2.2 Clinical ...

  9. Theory of conformational transitions of viral shells

    NASA Astrophysics Data System (ADS)

    Guérin, Thomas; Bruinsma, Robijn

    2007-12-01

    We propose a continuum theory for the conformational transitions of viral shells. Conformational transitions of viral shells, as encountered during viral maturation, are associated with a soft mode instability of the capsid proteins [F. Tama and C. L. Brooks, J. Mol. Biol. 345(2), 299 (2005)]. The continuum theory presented here is an adaptation of the Ginzburg-Landau theory of soft-mode structural phase transitions of solids to viral shells. The theory predicts that the conformational transitions are characterized by a pronounced softening of the shell elasticity in the critical region. We demonstrate that the thermodynamics of the conformational transition can be probed quantitatively by a micromechanical atomic force microscope study. The external force can drive a capsid into a state of phase coexistence characterized by a highly nonlinear force deformation curve.

  10. Viral fitness: definitions, measurement, and current insights

    USGS Publications Warehouse

    Wargo, Andrew R.; Kurath, Gael

    2012-01-01

    Viral fitness is an active area of research, with recent work involving an expanded number of human, non-human vertebrate, invertebrate, plant, and bacterial viruses. Many publications deal with RNA viruses associated with major disease emergence events, such as HIV-1, influenza virus, and Dengue virus. Study topics include drug resistance, immune escape, viral emergence, host jumps, mutation effects, quasispecies diversity, and mathematical models of viral fitness. Important recent trends include increasing use of in vivo systems to assess vertebrate virus fitness, and a broadening of research beyond replicative fitness to also investigate transmission fitness and epidemiologic fitness. This is essential for a more integrated understanding of overall viral fitness, with implications for disease management in the future.

  11. Viral and host control of cytomegalovirus maturation.

    PubMed

    Tandon, Ritesh; Mocarski, Edward S

    2012-08-01

    Maturation in herpesviruses initiates in the nucleus of the infected cell, with encapsidation of viral DNA to form nucleocapsids, and concludes with envelopment in the cytoplasm to form infectious virions that egress the cell. The entire process of virus maturation is orchestrated by protein-protein interactions and enzymatic activities of viral and host origin. Viral tegument proteins play important roles in maintaining the structural stability of capsids and directing the acquisition of virus envelope. Envelopment occurs at modified host membranes and exploits host vesicular trafficking. In this review, we summarize current knowledge of and concepts in human cytomegalovirus (HCMV) maturation and their parallels in other herpesviruses, with an emphasis on viral and host factors that regulate this process. PMID:22633075

  12. The contribution of viral genotype to plasma viral set-point in HIV infection.

    PubMed

    Hodcroft, Emma; Hadfield, Jarrod D; Fearnhill, Esther; Phillips, Andrew; Dunn, David; O'Shea, Siobhan; Pillay, Deenan; Leigh Brown, Andrew J

    2014-05-01

    Disease progression in HIV-infected individuals varies greatly, and while the environmental and host factors influencing this variation have been widely investigated, the viral contribution to variation in set-point viral load, a predictor of disease progression, is less clear. Previous studies, using transmission-pairs and analysis of phylogenetic signal in small numbers of individuals, have produced a wide range of viral genetic effect estimates. Here we present a novel application of a population-scale method based in quantitative genetics to estimate the viral genetic effect on set-point viral load in the UK subtype B HIV-1 epidemic, based on a very large data set. Analyzing the initial viral load and associated pol sequence, both taken before anti-retroviral therapy, of 8,483 patients, we estimate the proportion of variance in viral load explained by viral genetic effects to be 5.7% (CI 2.8-8.6%). We also estimated the change in viral load over time due to selection on the virus and environmental effects to be a decline of 0.05 log10 copies/mL/year, in contrast to recent studies which suggested a reported small increase in viral load over the last 20 years might be due to evolutionary changes in the virus. Our results suggest that in the UK epidemic, subtype B has a small but significant viral genetic effect on viral load. By allowing the analysis of large sample sizes, we expect our approach to be applicable to the estimation of the genetic contribution to traits in many organisms. PMID:24789308

  13. The Contribution of Viral Genotype to Plasma Viral Set-Point in HIV Infection

    PubMed Central

    Hodcroft, Emma; Hadfield, Jarrod D.; Fearnhill, Esther; Phillips, Andrew; Dunn, David; O'Shea, Siobhan; Pillay, Deenan; Leigh Brown, Andrew J.

    2014-01-01

    Disease progression in HIV-infected individuals varies greatly, and while the environmental and host factors influencing this variation have been widely investigated, the viral contribution to variation in set-point viral load, a predictor of disease progression, is less clear. Previous studies, using transmission-pairs and analysis of phylogenetic signal in small numbers of individuals, have produced a wide range of viral genetic effect estimates. Here we present a novel application of a population-scale method based in quantitative genetics to estimate the viral genetic effect on set-point viral load in the UK subtype B HIV-1 epidemic, based on a very large data set. Analyzing the initial viral load and associated pol sequence, both taken before anti-retroviral therapy, of 8,483 patients, we estimate the proportion of variance in viral load explained by viral genetic effects to be 5.7% (CI 2.8–8.6%). We also estimated the change in viral load over time due to selection on the virus and environmental effects to be a decline of 0.05 log10 copies/mL/year, in contrast to recent studies which suggested a reported small increase in viral load over the last 20 years might be due to evolutionary changes in the virus. Our results suggest that in the UK epidemic, subtype B has a small but significant viral genetic effect on viral load. By allowing the analysis of large sample sizes, we expect our approach to be applicable to the estimation of the genetic contribution to traits in many organisms. PMID:24789308

  14. A Comprehensive Collection of Systems Biology Data Characterizing the Host Response to Viral Infection

    SciTech Connect

    Aevermann, Brian; Pickett, Brett E.; Kumar, Sanjeev; Klem, Edward B.; Agnihothram, Sudhakar; Askovich, Peter S.; Bankhead, Armand; Bolles, Meagan; Carter, Victoria; Chang, Jean H.; Clauss, Therese RW; Dash, Pradyot; Diercks, Alan H.; Eisfeld, Amie J.; Ellis, Amy L.; Fan, Shufang; Ferris, Martin T.; Gralinski, Lisa; Green, Richard; Gritsenko, Marina A.; Hatta, Masato; Heegel, Robert A.; Jacobs, Jon M.; Jeng, Sophia; Josset, Laurence; Kaiser, Shari M.; Kelly, Sarah; Law, Gale L.; Li, Chengjun; Li, Jiangning; Long, Casey; Luna, Maria L.; Matzke, Melissa M.; McDermott, Jason E.; Menachery, Vineet; Metz, Thomas O.; Mitchell, Hugh D.; Monroe, Matthew E.; Navarro, Garnet; Neumann, Gabriele; Podyminogin, Rebecca L.; Purvine, Samuel O.; Rosenberger, Carrie; Sanders, Catherine J.; Schepmoes, Athena A.; Shukla, Anil K.; Sims, Amy; Sova, Pavel; Tam, Vincent C.; Tchitchek, Nicholas; Thomas, Paul G.; Tilton, Susan C.; Totura, Allison L.; Wang, Jing; Webb-Robertson, Bobbie-Jo M.; Wen, Ji; Weiss, Jeffrey M.; Yang, Feng; Yount, Boyd; Zhang, Qibin; Mcweeney, Shannon K.; Smith, Richard D.; Waters, Katrina M.; Kawaoka, Yoshihiro; Baric, Ralph; Aderem, Alan; Katze, Michael G.; Scheuermann, Richard H.

    2014-10-14

    The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archived at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). By comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection.

  15. Host behavior alters spiny lobster-viral disease dynamics: a simulation study.

    PubMed

    Dolan, Thomas W; Butler, Mark J; Shields, Jeffrey D

    2014-08-01

    Social behavior confers numerous benefits to animals but also risks, among them an increase in the spread of pathogenic diseases. We examined the trade-off between risk of predation and disease transmission under different scenarios of host spatial structure and disease avoidance behavior using a spatially explicit, individual-based model of the host pathogen interaction between juvenile Caribbean spiny lobster (Panulirus argus) and Panulirus argus Virus 1 (PaV1). Spiny lobsters are normally social but modify their behavior to avoid diseased conspecifics, a potentially effective means of reducing transmission but one rarely observed in the wild. We found that without lobster avoidance of diseased conspecifics, viral outbreaks grew in intensity and duration in simulations until the virus was maintained continuously at unrealistically high levels. However, when we invoked disease avoidance at empirically observed levels, the intensity and duration of outbreaks was reduced and the disease extirpated within five years. Increased lobster (host) spatial aggregation mimicking that which occurs when sponge shelters for lobsters are diminished by harmful algal blooms, did not significantly increase PaV1 transmission or persistence in lobster populations. On the contrary, behavioral aversion of diseased conspecifics effectively reduced viral prevalence, even when shelters were limited, which reduced shelter availability for all lobsters but increased predation, especially of infected lobsters. Therefore, avoidance of diseased conspecifics selects against transmission by contact, promotes alternative modes of transmission, and results in a more resilient host-pathogen system. PMID:25230484

  16. Involvement of Eukaryotic Small RNA Pathways in Host Defense and Viral Pathogenesis

    PubMed Central

    Hicks, Julie; Liu, Hsiao-Ching

    2013-01-01

    Post-transcriptional gene regulation by small RNAs is now established as an important branch of the gene regulatory system. Many different classes of small RNAs have been discovered; among these are short interfering RNAs (siRNAs) and microRNA (miRNAs). Though differences in the processing and function of small RNAs exist between plants and animals, both groups utilize small RNA-mediated gene regulation in response to pathogens. Host encoded miRNAs and siRNAs are generated from viral RNA function in host defense and pathogenic resistance in plants. In animals, miRNAs are key regulators in both immune system development and in immune function. Pathogens, in particular viruses, have evolved mechanisms to usurp the host’s small RNA-mediated regulatory system. Overall, small RNAs are a major component of host defense and immunity in eukaryotes. The goal of this review is to summarize our current knowledge of the involvement of eukaryotic small RNA pathways in host defense and viral pathogenesis. PMID:24178713

  17. Cryptosporidium Pathogenicity and Virulence

    PubMed Central

    Bouzid, Maha; Chalmers, Rachel M.; Tyler, Kevin M.

    2013-01-01

    Cryptosporidium is a protozoan parasite of medical and veterinary importance that causes gastroenteritis in a variety of vertebrate hosts. Several studies have reported different degrees of pathogenicity and virulence among Cryptosporidium species and isolates of the same species as well as evidence of variation in host susceptibility to infection. The identification and validation of Cryptosporidium virulence factors have been hindered by the renowned difficulties pertaining to the in vitro culture and genetic manipulation of this parasite. Nevertheless, substantial progress has been made in identifying putative virulence factors for Cryptosporidium. This progress has been accelerated since the publication of the Cryptosporidium parvum and C. hominis genomes, with the characterization of over 25 putative virulence factors identified by using a variety of immunological and molecular techniques and which are proposed to be involved in aspects of host-pathogen interactions from adhesion and locomotion to invasion and proliferation. Progress has also been made in the contribution of host factors that are associated with variations in both the severity and risk of infection. Here we provide a review comprised of the current state of knowledge on Cryptosporidium infectivity, pathogenesis, and transmissibility in light of our contemporary understanding of microbial virulence. PMID:23297262

  18. Proteomic screening of variola virus reveals a unique NF-?B inhibitor that is highly conserved among pathogenic orthopoxviruses

    PubMed Central

    Mohamed, Mohamed R.; Rahman, Masmudur M.; Lanchbury, Jerry S.; Shattuck, Donna; Neff, Chris; Dufford, Max; van Buuren, Nick; Fagan, Katharine; Barry, Michele; Smith, Scott; Damon, Inger; McFadden, Grant

    2009-01-01

    Identification of the binary interactions between viral and host proteins has become a valuable tool for investigating viral tropism and pathogenesis. Here, we present the first systematic protein interaction screening of the unique variola virus proteome by using yeast 2-hybrid screening against a variety of human cDNA libraries. Several protein–protein interactions were identified, including an interaction between variola G1R, an ankryin/F-box containing protein, and human nuclear factor kappa-B1 (NF-?B1)/p105. This represents the first direct interaction between a pathogen-encoded protein and NF-?B1/p105. Orthologs of G1R are present in a variety of pathogenic orthopoxviruses, but not in vaccinia virus, and expression of any one of these viral proteins blocks NF-?B signaling in human cells. Thus, proteomic screening of variola virus has the potential to uncover modulators of the human innate antiviral responses. PMID:19451633

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

    PubMed

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

    2015-02-01

    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

  20. Cytopathic bovine viral diarrhea viruses (BVDV): emerging pestiviruses doomed to extinction.

    PubMed

    Peterhans, Ernst; Bachofen, Claudia; Stalder, Hanspeter; Schweizer, Matthias

    2010-01-01

    Bovine viral diarrhea virus (BVDV), a Flaviviridae pestivirus, is arguably one of the most widespread cattle pathogens worldwide. Each of its two genotypes has two biotypes, non-cytopathic (ncp) and cytopathic (cp). Only the ncp biotype of BVDV may establish persistent infection in the fetus when infecting a dam early in gestation, a time point which predates maturity of the adaptive immune system. Such fetuses may develop and be born healthy but remain infected for life. Due to this early initiation of fetal infection and to the expression of interferon antagonistic proteins, persistently infected (PI) animals remain immunotolerant to the infecting viral strain. Although only accounting for some 1% of all animals in regions where BVDV is endemic, PI animals ensure the viral persistence in the host population. These animals may, however, develop the fatal mucosal disease, which is characterized by widespread lesions in the gastrointestinal tract. Cp BVD virus, in addition to the persisting ncp biotype, can be isolated from such animals. The cp viruses are characterized by unrestrained genome replication, and their emergence from the persisting ncp ones is due to mutations that are unique in each virus analyzed. They include recombinations with host cell mRNA, gene translocations and duplications, and point mutations. Cytopathic BVD viruses fail to establish chains of infection and are unable to cause persistent infection. Hence, these viruses illustrate a case of "viral emergence to extinction" - irrelevant for BVDV evolution, but fatal for the PI host. PMID:20197026

  1. Cytopathic bovine viral diarrhea viruses (BVDV): emerging pestiviruses doomed to extinction

    PubMed Central

    Peterhans, Ernst; Bachofen, Claudia; Stalder, Hanspeter; Schweizer, Matthias

    2010-01-01

    Bovine viral diarrhea virus (BVDV), a Flaviviridae pestivirus, is arguably one of the most widespread cattle pathogens worldwide. Each of its two genotypes has two biotypes, non-cytopathic (ncp) and cytopathic (cp). Only the ncp biotype of BVDV may establish persistent infection in the fetus when infecting a dam early in gestation, a time point which predates maturity of the adaptive immune system. Such fetuses may develop and be born healthy but remain infected for life. Due to this early initiation of fetal infection and to the expression of interferon antagonistic proteins, persistently infected (PI) animals remain immunotolerant to the infecting viral strain. Although only accounting for some 1% of all animals in regions where BVDV is endemic, PI animals ensure the viral persistence in the host population. These animals may, however, develop the fatal mucosal disease, which is characterized by widespread lesions in the gastrointestinal tract. Cp BVD virus, in addition to the persisting ncp biotype, can be isolated from such animals. The cp viruses are characterized by unrestrained genome replication, and their emergence from the persisting ncp ones is due to mutations that are unique in each virus analyzed. They include recombinations with host cell mRNA, gene translocations and duplications, and point mutations. Cytopathic BVD viruses fail to establish chains of infection and are unable to cause persistent infection. Hence, these viruses illustrate a case of “viral emergence to extinction” – irrelevant for BVDV evolution, but fatal for the PI host. PMID:20197026

  2. Avian influenza H5N1 viral and bird migration networks in Asia.

    PubMed

    Tian, Huaiyu; Zhou, Sen; Dong, Lu; Van Boeckel, Thomas P; Cui, Yujun; Wu, Yarong; Cazelles, Bernard; Huang, Shanqian; Yang, Ruifu; Grenfell, Bryan T; Xu, Bing

    2015-01-01

    The spatial spread of the highly pathogenic avian influenza virus H5N1 and its long-term persistence in Asia have resulted in avian influenza panzootics and enormous economic losses in the poultry sector. However, an understanding of the regional long-distance transmission and seasonal patterns of the virus is still lacking. In this study, we present a phylogeographic approach to reconstruct the viral migration network. We show that within each wild fowl migratory flyway, the timing of H5N1 outbreaks and viral migrations are closely associated, but little viral transmission was observed between the flyways. The bird migration network is shown to better reflect the observed viral gene sequence data than other networks and contributes to seasonal H5N1 epidemics in local regions and its large-scale transmission along flyways. These findings have potentially far-reaching consequences, improving our understanding of how bird migration drives the periodic reemergence of H5N1 in Asia. PMID:25535385

  3. Averaging of Viral Envelope Glycoprotein Spikes from Electron Cryotomography Reconstructions using Jsubtomo

    PubMed Central

    Huiskonen, Juha T.; Parsy, Marie-Laure; Li, Sai; Bitto, David; Renner, Max; Bowden, Thomas A.

    2014-01-01

    Enveloped viruses utilize membrane glycoproteins on their surface to mediate entry into host cells. Three-dimensional structural analysis of these glycoprotein ‘spikes’ is often technically challenging but important for understanding viral pathogenesis and in drug design. Here, a protocol is presented for viral spike structure determination through computational averaging of electron cryo-tomography data. Electron cryo-tomography is a technique in electron microscopy used to derive three-dimensional tomographic volume reconstructions, or tomograms, of pleomorphic biological specimens such as membrane viruses in a near-native, frozen-hydrated state. These tomograms reveal structures of interest in three dimensions, albeit at low resolution. Computational averaging of sub-volumes, or sub-tomograms, is necessary to obtain higher resolution detail of repeating structural motifs, such as viral glycoprotein spikes. A detailed computational approach for aligning and averaging sub-tomograms using the Jsubtomo software package is outlined. This approach enables visualization of the structure of viral glycoprotein spikes to a resolution in the range of 20-40 Å and study of the study of higher order spike-to-spike interactions on the virion membrane. Typical results are presented for Bunyamwera virus, an enveloped virus from the family Bunyaviridae. This family is a structurally diverse group of pathogens posing a threat to human and animal health. PMID:25350719

  4. Avian influenza H5N1 viral and bird migration networks in Asia

    PubMed Central

    Tian, Huaiyu; Zhou, Sen; Dong, Lu; Van Boeckel, Thomas P.; Cui, Yujun; Wu, Yarong; Cazelles, Bernard; Huang, Shanqian; Yang, Ruifu; Grenfell, Bryan T.; Xu, Bing

    2015-01-01

    The spatial spread of the highly pathogenic avian influenza virus H5N1 and its long-term persistence in Asia have resulted in avian influenza panzootics and enormous economic losses in the poultry sector. However, an understanding of the regional long-distance transmission and seasonal patterns of the virus is still lacking. In this study, we present a phylogeographic approach to reconstruct the viral migration network. We show that within each wild fowl migratory flyway, the timing of H5N1 outbreaks and viral migrations are closely associated, but little viral transmission was observed between the flyways. The bird migration network is shown to better reflect the observed viral gene sequence data than other networks and contributes to seasonal H5N1 epidemics in local regions and its large-scale transmission along flyways. These findings have potentially far-reaching consequences, improving our understanding of how bird migration drives the periodic reemergence of H5N1 in Asia. PMID:25535385

  5. QuRe: software for viral quasispecies reconstruction from next-generation sequencing data

    PubMed Central

    Prosperi, Mattia C. F.; Salemi, Marco

    2012-01-01

    Summary: Next-generation sequencing (NGS) is an ideal framework for the characterization of highly variable pathogens, with a deep resolution able to capture minority variants. However, the reconstruction of all variants of a viral population infecting a host is a challenging task for genome regions larger than the average NGS read length. QuRe is a program for viral quasispecies reconstruction, specifically developed to analyze long read (>100 bp) NGS data. The software performs alignments of sequence fragments against a reference genome, finds an optimal division of the genome into sliding windows based on coverage and diversity and attempts to reconstruct all the individual sequences of the viral quasispecies—along with their prevalence—using a heuristic algorithm, which matches multinomial distributions of distinct viral variants overlapping across the genome division. QuRe comes with a built-in Poisson error correction method and a post-reconstruction probabilistic clustering, both parameterized on given error rates in homopolymeric and non-homopolymeric regions. Availability: QuRe is platform-independent, multi-threaded software implemented in Java. It is distributed under the GNU General Public License, available at https://sourceforge.net/projects/qure/. Contact: ahnven@yahoo.it; ahnven@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:22088846

  6. The Toll-Dorsal Pathway Is Required for Resistance to Viral Oral Infection in Drosophila

    PubMed Central

    Ferreira, Álvaro Gil; Naylor, Huw; Esteves, Sara Santana; Pais, Inês Silva; Martins, Nelson Eduardo; Teixeira, Luis

    2014-01-01

    Pathogen entry route can have a strong impact on the result of microbial infections in different hosts, including insects. Drosophila melanogaster has been a successful model system to study the immune response to systemic viral infection. Here we investigate the role of the Toll pathway in resistance to oral viral infection in D. melanogaster. We show that several Toll pathway components, including Spätzle, Toll, Pelle and the NF-kB-like transcription factor Dorsal, are required to resist oral infection with Drosophila C virus. Furthermore, in the fat body Dorsal is translocated from the cytoplasm to the nucleus and a Toll pathway target gene reporter is upregulated in response to Drosophila C Virus infection. This pathway also mediates resistance to several other RNA viruses (Cricket paralysis virus, Flock House virus, and Nora virus). Compared with control, viral titres are highly increased in Toll pathway mutants. The role of the Toll pathway in resistance to viruses in D. melanogaster is restricted to oral infection since we do not observe a phenotype associated with systemic infection. We also show that Wolbachia and other Drosophila-associated microbiota do not interact with the Toll pathway-mediated resistance to oral infection. We therefore identify the Toll pathway as a new general inducible pathway that mediates strong resistance to viruses with a route-specific role. These results contribute to a better understanding of viral oral infection resistance in insects, which is particularly relevant in the context of transmission of arboviruses by insect vectors. PMID:25473839

  7. The Toll-dorsal pathway is required for resistance to viral oral infection in Drosophila.

    PubMed

    Ferreira, Álvaro Gil; Naylor, Huw; Esteves, Sara Santana; Pais, Inês Silva; Martins, Nelson Eduardo; Teixeira, Luis

    2014-12-01

    Pathogen entry route can have a strong impact on the result of microbial infections in different hosts, including insects. Drosophila melanogaster has been a successful model system to study the immune response to systemic viral infection. Here we investigate the role of the Toll pathway in resistance to oral viral infection in D. melanogaster. We show that several Toll pathway components, including Spätzle, Toll, Pelle and the NF-kB-like transcription factor Dorsal, are required to resist oral infection with Drosophila C virus. Furthermore, in the fat body Dorsal is translocated from the cytoplasm to the nucleus and a Toll pathway target gene reporter is upregulated in response to Drosophila C Virus infection. This pathway also mediates resistance to several other RNA viruses (Cricket paralysis virus, Flock House virus, and Nora virus). Compared with control, viral titres are highly increased in Toll pathway mutants. The role of the Toll pathway in resistance to viruses in D. melanogaster is restricted to oral infection since we do not observe a phenotype associated with systemic infection. We also show that Wolbachia and other Drosophila-associated microbiota do not interact with the Toll pathway-mediated resistance to oral infection. We therefore identify the Toll pathway as a new general inducible pathway that mediates strong resistance to viruses with a route-specific role. These results contribute to a better understanding of viral oral infection resistance in insects, which is particularly relevant in the context of transmission of arboviruses by insect vectors. PMID:25473839

  8. Antiviral and metabolic gene expression responses to viral infection in Atlantic salmon (Salmo salar).

    PubMed

    Heidari, Zeynab; Tinsley, John; Bickerdike, Ralph; McLoughlin, Marian F; Zou, Jun; Martin, Samuel A M

    2015-02-01

    Salmonid alphavirus (SAV), the aetiological agent of pancreas disease, is recognized as a serious pathogen of farmed Atlantic salmon. This disease results in loss of weight followed by poor growth of surviving fish, as such it is viewed as a wasting disease. SAV and other chronic disease causing viruses affect the heart and skeletal muscle tissues, at present the mechanisms by which pathology occurs is unknown. The relationship between antiviral activity and other physiological parameters especially in skeletal muscle are currently not examined in depth in fish. An experimental SAV (isotype 3) infection was carried out using a cohabitation approach, from which samples were collected at 0, 4, 8 & 12 week post challenge. Maximum viral load in the muscle tissue was 4 weeks post infection which was reduced at 8 weeks and undetectable by 12 weeks. Histopathology score peaked at 4 weeks post infection in pancreas and heart whereas there was maximum damage in skeletal muscle at 8 weeks. The peak expression of antiviral immune genes coincided with the viral load. Several genes involved in protein degradation were increased following infection including atrogin-1 and cathepsin D, at 4 weeks post challenge suggesting reallocation of amino acid reserves. Taken together, these observations increase our understanding of salmon poor growth during viral infection, and will serve as a basis to develop strategies to manage this viral wasting disease. PMID:25462555

  9. Seroprevalence of viral childhood infections in Eritrea

    Microsoft Academic Search

    T Tolfvenstam; M Enbom; H Ghebrekidan; U Rudén; A Linde; M Grandien; B Wahren

    2000-01-01

    Background: The seroprevalence of viral childhood infections in Africa has not been thoroughly investigated. The relatively recently discovered human parvovirus B19 (B19) and human herpesvirus 6 (HHV-6) have received particularly little attention.Objective: To investigate the seroprevalence of viral childhood infections in different Eritrean populations and to define groups at high risk for infection.Study design: Five population groups in Eritrea have

  10. Viral Interplay with the Host Sumoylation System

    Microsoft Academic Search

    Adeline F. Deyrieux; Van G. Wilson

    \\u000a Viruses have elaborate means to regulate cellular transcription in order to create a cellular environment that facilitates\\u000a viral survival and reproduction. This includes enhancing viral macromolecular synthesis and preventing antiviral responses\\u000a such as apoptosis and cell cycle arrest. There are numerous mechanisms by which viruses mediate their effects on the host\\u000a cell, and this includes targeting various cellular post-translational modification

  11. The nucleolus – a gateway to viral infection?

    Microsoft Academic Search

    J. A. Hiscox

    2002-01-01

    Summary.  ?A number of viruses and viral proteins interact with a dynamic sub-nuclear structure called the nucleolus. The nucleolus\\u000a is present during interphase in mammalian cells and is the site of ribosome biogenesis, and has been implicated in controlling\\u000a regulatory processes such as the cell cycle. Viruses interact with the nucleolus and its antigens; viral proteins co-localise\\u000a with factors such as

  12. Viral Replication and Lung Lesions in BALB/c Mice Experimentally Inoculated with Avian Metapneumovirus Subgroup C Isolated from Chickens

    PubMed Central

    She, Ruiping; Hu, Fengjiao; Wang, Jing; Yan, Xu; Zhang, Chunyan; Liu, Shuhang; Quan, Rong; Li, Zixuan; Du, Fang; Wei, Ting; Liu, Jue

    2014-01-01

    Avian metapneumovirus (aMPV) emerged as an important respiratory pathogen causing acute respiratory tract infection in avian species. Here we used a chicken aMPV subgroup C (aMPV/C) isolate to inoculate experimentally BALB/c mice and found that the aMPV/C can efficiently replicate and persist in the lungs of mice for at least 21 days with a peak viral load at day 6 postinoculation. Lung pathological changes were characterized by increased inflammatory cells. Immunochemical assay showed the presence of viral antigens in the lungs and significant upregulation of pulmonary inflammatory cytokines and chemokines including MCP-1, MIP-1?, RANTES, IL-1?, IFN-?, and TNF-? were detected following inoculation. These results indicate for the first time that chicken aMPV/C may replicate in the lung of mice. Whether aMPV/C has potential as zoonotic pathogen, further investigation will be required. PMID:24637582

  13. Viral Metagenomics: MetaView Software

    SciTech Connect

    Zhou, C; Smith, J

    2007-10-22

    The purpose of this report is to design and develop a tool for analysis of raw sequence read data from viral metagenomics experiments. The tool should compare read sequences of known viral nucleic acid sequence data and enable a user to attempt to determine, with some degree of confidence, what virus groups may be present in the sample. This project was conducted in two phases. In phase 1 we surveyed the literature and examined existing metagenomics tools to educate ourselves and to more precisely define the problem of analyzing raw read data from viral metagenomic experiments. In phase 2 we devised an approach and built a prototype code and database. This code takes viral metagenomic read data in fasta format as input and accesses all complete viral genomes from Kpath for sequence comparison. The system executes at the UNIX command line, producing output that is stored in an Oracle relational database. We provide here a description of the approach we came up with for handling un-assembled, short read data sets from viral metagenomics experiments. We include a discussion of the current MetaView code capabilities and additional functionality that we believe should be added, should additional funding be acquired to continue the work.

  14. Generating viral metagenomes from the coral holobiont

    PubMed Central

    Wood-Charlson, Elisha M.; Suttle, Curtis A.; van Oppen, Madeleine J. H.

    2014-01-01

    Reef-building corals comprise multipartite symbioses where the cnidarian animal is host to an array of eukaryotic and prokaryotic organisms, and the viruses that infect them. These viruses are critical elements of the coral holobiont, serving not only as agents of mortality, but also as potential vectors for lateral gene flow, and as elements encoding a variety of auxiliary metabolic functions. Consequently, understanding the functioning and health of the coral holobiont requires detailed knowledge of the associated viral assemblage and its function. Currently, the most tractable way of uncovering viral diversity and function is through metagenomic approaches, which is inherently difficult in corals because of the complex holobiont community, an extracellular mucus layer that all corals secrete, and the variety of sizes and structures of nucleic acids found in viruses. Here we present the first protocol for isolating, purifying and amplifying viral nucleic acids from corals based on mechanical disruption of cells. This method produces at least 50% higher yields of viral nucleic acids, has very low levels of cellular sequence contamination and captures wider viral diversity than previously used chemical-based extraction methods. We demonstrate that our mechanical-based method profiles a greater diversity of DNA and RNA genomes, including virus groups such as Retro-transcribing and ssRNA viruses, which are absent from metagenomes generated via chemical-based methods. In addition, we briefly present (and make publically available) the first paired DNA and RNA viral metagenomes from the coral Acropora tenuis. PMID:24847321

  15. Generating viral metagenomes from the coral holobiont.

    PubMed

    Weynberg, Karen D; Wood-Charlson, Elisha M; Suttle, Curtis A; van Oppen, Madeleine J H

    2014-01-01

    Reef-building corals comprise multipartite symbioses where the cnidarian animal is host to an array of eukaryotic and prokaryotic organisms, and the viruses that infect them. These viruses are critical elements of the coral holobiont, serving not only as agents of mortality, but also as potential vectors for lateral gene flow, and as elements encoding a variety of auxiliary metabolic functions. Consequently, understanding the functioning and health of the coral holobiont requires detailed knowledge of the associated viral assemblage and its function. Currently, the most tractable way of uncovering viral diversity and function is through metagenomic approaches, which is inherently difficult in corals because of the complex holobiont community, an extracellular mucus layer that all corals secrete, and the variety of sizes and structures of nucleic acids found in viruses. Here we present the first protocol for isolating, purifying and amplifying viral nucleic acids from corals based on mechanical disruption of cells. This method produces at least 50% higher yields of viral nucleic acids, has very low levels of cellular sequence contamination and captures wider viral diversity than previously used chemical-based extraction methods. We demonstrate that our mechanical-based method profiles a greater diversity of DNA and RNA genomes, including virus groups such as Retro-transcribing and ssRNA viruses, which are absent from metagenomes generated via chemical-based methods. In addition, we briefly present (and make publically available) the first paired DNA and RNA viral metagenomes from the coral Acropora tenuis. PMID:24847321

  16. Macrolide Therapy in Respiratory Viral Infections

    PubMed Central

    Min, Jin-Young; Jang, Yong Ju

    2012-01-01

    Background. Macrolides have received considerable attention for their anti-inflammatory and immunomodulatory actions beyond the antibacterial effect. These two properties may ensure some efficacy in a wide spectrum of respiratory viral infections. We aimed to summarize the properties of macrolides and their efficacy in a range of respiratory viral infection. Methods. A search of electronic journal articles through PubMed was performed using combinations of the following keywords including macrolides and respiratory viral infection. Results. Both in vitro and in vivo studies have provided evidence of their efficacy in respiratory viral infections including rhinovirus (RV), respiratory syncytial virus (RSV), and influenza virus. Much data showed that macrolides reduced viral titers of RV ICAM-1, which is the receptor for RV, and RV infection-induced cytokines including IL-1?, IL-6, IL-8, and TNF-?. Macrolides also reduced the release of proinflammatory cytokines which were induced by RSV infection, viral titers, RNA of RSV replication, and the susceptibility to RSV infection partly through the reduced expression of activated RhoA which is an RSV receptor. Similar effects of macrolides on the influenza virus infection and augmentation of the IL-12 by macrolides which is essential in reducing virus yield were revealed. Conclusion. This paper provides an overview on the properties of macrolides and their efficacy in various respiratory diseases. PMID:22719178

  17. The Role of Viral and Host MicroRNAs in the Aujeszky’s Disease Virus during the Infection Process

    PubMed Central

    Timoneda, Oriol; Núñez-Hernández, Fernando; Balcells, Ingrid; Muñoz, Marta; Castelló, Anna; Vera, Gonzalo; Pérez, Lester J.; Egea, Raquel; Mir, Gisela; Córdoba, Sarai; Rosell, Rosa; Segalés, Joaquim; Tomàs, Anna; Sánchez, Armand; Núñez, José I.

    2014-01-01

    Porcine production is a primary market in the world economy. Controlling swine diseases in the farm is essential in order to achieve the sector necessities. Aujeszky’s disease is a viral condition affecting pigs and is endemic in many countries of the world, causing important economic losses in the swine industry. microRNAs (miRNAs) are non-coding RNAs which modulates gene expression in animals, plants and viruses. With the aim of understanding miRNA roles during the Aujeszky’s disease virus [ADV] (also known as suid herpesvirus type 1 [SuHV-1]) infection, the expression profiles of host and viral miRNAs were determined through deep sequencing in SuHV-1 infected porcine cell line (PK-15) and in an animal experimental SuHV-1 infection with virulent (NIA-3) and attenuated (Begonia) strains. In the in vivo approach miR-206, miR-133a, miR-133b and miR-378 presented differential expression between virus strains infection. In the in vitro approach, most miRNAs were down-regulated in infected groups. miR-92a and miR-92b-3p were up-regulated in Begonia infected samples. Functional analysis of all this over expressed miRNAs during the infection revealed their association in pathways related to viral infection processes and immune response. Furthermore, 8 viral miRNAs were detected by stem loop RT-qPCR in both in vitro and in vivo approaches, presenting a gene regulatory network affecting 59 viral genes. Most described viral miRNAs were related to Large Latency Transcript (LLT) and to viral transcription activators EP0 and IE180, and also to regulatory genes regarding their important roles in the host – pathogen interaction during viral infection. PMID:24475202

  18. A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China

    PubMed Central

    He, Ying; Lin, Guang-Yu; Wang, Qiong; Cai, Xiao-Ying; Zhang, Yin-Hui; Lin, Chuang-Xing; Lu, Chang-Dong; Lu, Xue-Dong

    2014-01-01

    Background The epidemiology of local viral etiologies is essential for the management of viral respiratory tract infections. Limited data are available in China to describe the epidemiology of viral respiratory infections, especially in small–medium cities and rural areas. Objectives To determine the viral etiology and seasonality of acute respiratory infections in hospitalized children, a 3-year study was conducted in Shenzhen, China. Methods Nasopharyngeal aspirates from eligible children were collected. Influenza and other respiratory viruses were tested by molecular assays simultaneously. Data were analyzed to describe the frequency and seasonality. Results Of the 2025 children enrolled in the study, 971 (48·0%) were positive for at least one viral pathogen, in which 890 (91·7%) were <4 years of age. The three most prevalent viruses were influenza A (IAV; 35·8%), respiratory syncytial virus (RSV; 30·5%) and human rhinovirus (HRV; 21·5%). Co-infections were found in 302 cases (31·1%), and dual viral infection was dominant. RSV, HRV and IAV were the most frequent viral agents involved in co-infection. On the whole, the obvious seasonal peaks mainly from March to May were observed with peak strength varying from 1 year to another. Conclusions This study provides a basic profile of the epidemiology of acute respiratory viral infection in hospitalized children in Shenzhen. The spectrum of viruses in the study site is similar to that in other places, but the seasonality is closely related to geographic position, different from that in big cities in northern China and neighboring Hong Kong. PMID:24828783

  19. Multiplex detection of respiratory pathogens

    DOEpatents

    McBride, Mary (Brentwood, CA); Slezak, Thomas (Livermore, CA); Birch, James M. (Albany, CA)

    2012-07-31

    Described are kits and methods useful for detection of respiratory pathogens (influenza A (including subtyping capability for H1, H3, H5 and H7 subtypes) influenza B, parainfluenza (type 2), respiratory syncytial virus, and adenovirus) in a sample. Genomic sequence information from the respiratory pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay to successfully identify the presence or absence of pathogens in a sample.

  20. Genome comparison of bacterial pathogens.

    PubMed

    Wassenaar, T M; Bohlin, J; Binnewies, T T; Ussery, D W

    2009-01-01

    Bacterial pathogens are being sequenced at an increasing rate. To many microbiologists, it appears that there simply is not enough time to digest all the information suddenly available. In this chapter we present several tools for comparison of sequenced pathogenic genomes, and discuss differences between pathogens and non-pathogens. The presented tools allow comparison of large numbers of genomes in a hypothesis-driven manner. Visualization of the results is very important for clear presentation of the results and various ways of graphical representation are introduced. PMID:19696490