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. 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...

  3. Phylogeny and differentiation of reptilian and amphibian ranaviruses detected in Europe.

    PubMed

    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

  4. Persistence of an amphibian ranavirus in aquatic communities.

    PubMed

    Johnson, A F; Brunner, J L

    2014-09-30

    Host-parasite dynamics can be strongly influenced by interactions with other members of the biotic community, particularly when the parasite spends some fraction of its life in the environment unprotected by its host. Ranaviruses-often lethal viruses of cold-blooded vertebrate hosts transmitted by direct contact, and via water and fomites-offer an interesting system for understanding these community influences. Previous laboratory studies have shown that ranaviruses can persist for anywhere from days to years, depending on the conditions, with much longer times under sterile conditions. To address the role of the biotic community and particulate matter on ranavirus persistence, we experimentally inoculated filter-sterilized, UV-treated, and unmanipulated pond water with a Frog virus 3 (FV3)-like Ranavirus and took samples over 78 d, quantifying viral titers with real-time quantitative PCR and plaque assays. Viral counts dropped quickly in all treatments, by an order of magnitude in under a day in unmanipulated pond water and in 8 d in filter-sterilized pond water. In a second experiment, we measured viral titers over 24 h in virus-spiked spring water with Daphnia pulex. Presence of D. pulex reduced the concentration of infectious ranavirus, but not viral DNA, by an order of magnitude in 24 h. D. pulex themselves did not accumulate the virus. We conclude that both microbial and zooplanktonic communities can play an important role in ranavirus epidemiology, rapidly inactivating ranavirus in the water and thereby minimizing environmental transmission. We suspect that interactions with the biotic community will be important for most pathogens with environmental resting or transmission stages. PMID:25266900

  5. 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

  6. 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).

  7. 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

  8. 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...

  9. Influence of Dendritic Cells on Viral Pathogenicity

    Microsoft Academic Search

    Giulia Freer; Donatella Matteucci

    2009-01-01

    Although most viral infections cause minor, if any, symptoms, a certain number result in serious illness. Viral disease symptoms result both from direct viral replication within host cells and from indirect immunopathological consequences. Dendritic cells (DCs) are key determinants of viral disease outcome; they activate immune responses during viral infection and direct T cells toward distinct T helper type responses.

  10. Establishment of three cell lines from Chinese giant salamander and their sensitivities to the wild-type and recombinant ranavirus.

    PubMed

    Yuan, Jiang-Di; Chen, Zhong-Yuan; Huang, Xing; Gao, Xiao-Chan; Zhang, Qi-Ya

    2015-01-01

    Known as lethal pathogens, Ranaviruses have been identified in diseased fish, amphibians (including Chinese giant salamander Andrias davidianus, the world's largest amphibian) and reptiles, causing organ necrosis and systemic hemorrhage. Here, three Chinese giant salamander cell lines, thymus cell line (GSTC), spleen cell line (GSSC) and kidney cell line (GSKC) were initially established. Their sensitivities to ranaviruses, wild-type Andrias davidianus ranavirus (ADRV) and recombinant Rana grylio virus carrying EGFP gene (rRGV-EGFP) were tested. Temporal transcription pattern of ranavirus major capsid protein (MCP), fluorescence and electron microscopy observations showed that both the wild-type and recombinant ranavirus could replicate in the cell lines. PMID:26070783

  11. Ranaviruses: Cold Blooded Killers!

    E-print Network

    Gray, Matthew

    ) 34% (12%, 23%) #12;2 History of Ranavirus Die-offs First Isolated: ·Dr. Allan Granoff ·Rana pipiens (1962) First Large-scale Die-offs: ·St. Jude Hospital g ·Dr. Andrew Cunningham ·Rana temporaria (1992

  12. Molecular constraints to interspecies transmission of viral pathogens

    Microsoft Academic Search

    Richard Webby; Erich Hoffmann; Robert Webster

    2004-01-01

    The successful replication of a viral pathogen in a host is a complex process involving many interactions. These interactions develop from the coevolution of pathogen and host and often lead to a species specificity of the virus that can make interspecies transmissions difficult. Nevertheless, viruses do sporadically cross species barriers into other host populations, including humans. In zoonotic infections, many

  13. Matthew J. Gray Ranaviruses

    E-print Network

    Gray, Matthew

    Dept of Conservation Amanda Duffus, Zoological Society of London Megan Gahl, University of New Brunswick David Green, USGS Nathan Haislip, University of Tennessee Jason Hoverman, University of Tennessee, Ranavirus Die-offs are Widespread! D. Green, unpubl. data #12;Common Species Only? #12;Case Examples Japan

  14. High Occupancy of Stream Salamanders Despite High Ranavirus Prevalence in a Southern Appalachians Watershed

    E-print Network

    Gray, Matthew

    of Veterinary Medicine, University of Georgia, Athens, GA Abstract: The interactive effects of environmental, Eurycea, Gyrinophilus, occupancy, monitoring, disease surveillance INTRODUCTION Two emerging pathogensHigh Occupancy of Stream Salamanders Despite High Ranavirus Prevalence in a Southern Appalachians

  15. Comparative analysis of viral pathogens and potential indicators in shellfish.

    PubMed

    Muniain-Mujika, I; Calvo, M; Lucena, F; Girones, R

    2003-05-25

    Shellfish can be responsible of outbreaks of infectious diseases and current health measures do not guarantee the absence of viral pathogens in this product. Here we examine the presence of pathogenic viruses and potential indicators in shellfish in a comparative analysis.Sixty shellfish samples collected in three areas with different levels of faecal contamination were analysed for Escherichia coli, total coliforms, Clostridium perfringens, somatic coliphages, F-specific phages of RNA (F-RNA), bacteriophages infecting Bacteroides fragilis RYC2056, human adenovirus, enterovirus and hepatitis A virus (HAV). Viruses were eluted in a glycine buffer at pH 10. The overall percentage of viral pathogens detected was 47% for human adenoviruses, 19% for enteroviruses and 24% for HAV. Since all the samples positive for enterovirus and HAV were also positives for human adenovirus, the latter may be considered useful as a molecular index of viral contamination in shellfish. No significant differences in the bioaccumulation of bacteria and bacteriophages for oysters or mussels were observed. It was found that the probability of detection of any of the pathogenic virus decreases as the temperature of shellfish growing waters increases. However, the probability of detecting viruses increases when phages of B. fragilis are found. Although more data are needed in order to fulfil the need of viral indicators for controlling the presence of human viruses in shellfish, the obtained results indicate that phages infecting B. fragilis RYC2056 could be a suitable group of bacteriophages to be used as an indicator of the presence of viruses in shellfish. PMID:12672594

  16. Morphological changes in amphibian and fish cell lines infected with Andrias davidianus ranavirus.

    PubMed

    Gao, X C; Chen, Z Y; Yuan, J D; Zhang, Q Y

    2015-01-01

    Andrias davidianus ranavirus (ADRV) is an emerging viral pathogen that causes severe disease in Chinese giant salamanders, the largest extant amphibian in the world. A fish cell line, Epithelioma papulosum cyprinid (EPC), and a new amphibian cell line, Chinese giant salamander spleen cell (GSSC), were infected with ADRV and observed by light and electron microscopy. The morphological changes in these two cell lines infected with ADRV were compared. Cytopathic effect (CPE) began with rounding of the cells, progressing to cell detachment in the cell monolayer, followed by cell lysis. Significant CPE was visualized as early as 24 h post infection (hpi) in EPC cells and at 36 hpi in GSSC cells. Microscopical examination showed clear and significant CPE in EPC cells, while less extensive and irregular CPE with some adherent cells remaining was observed in GSSC cells. Following ADRV infection, CPE became more extensive. Transmission electron micrographs showed many virus particles around cytoplasmic vacuoles, formed as crystalline arrays or scattered in the cytoplasm of infected cells. Infected cells showed alteration in nuclear morphology, with condensed and marginalized nuclear chromatin on the inner aspect of the nuclear membrane and formation of a cytoplasmic viromatrix adjacent to the nucleus in both cell lines. Some virus particles were also detected in the nucleus of infected GSSC cells. Both cell lines are able to support replication of ADRV and can therefore be used to investigate amphibian ranaviruses. PMID:25728809

  17. Immunohistochemical staining for ranaviruses Introduction: Ranaviruses negatively impact amphibian populations

    E-print Network

    Gray, Matthew

    (Trachemys scripta elegans) that were challenged with 4 different FV3-like ranavirus isolates (FV3, isolate, no staining was observed in the tissues of the red eared slider (Trachemys scripta elegans; Fig. 3

  18. 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

  19. 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

  20. LOW LEVEL DETECTION OF VIRAL PATHOGENS BY A SURFACE-ENHANCED RAMAN SCATTERING BASED IMMUNOASSAY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    E-print Network

    Crews, Stephen

    Direct and indirect effects of viral pathogens and the environment on invasive grass fecundity, University of North Carolina, Chapel Hill, NC 27599, USA Summary 1. Pathogens can have strong effects on their hosts and can be important determinants of biological invasions. In natural systems, host­pathogen

  2. 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

  3. Viral pathogen production in a wild grass host driven by host growth and soil nitrogen.

    PubMed

    Whitaker, Briana K; Rúa, Megan A; Mitchell, Charles E

    2015-08-01

    Nutrient limitation is a basic ecological constraint that has received little attention in studies on virus production and disease dynamics. Nutrient availability could directly limit the production of viral nucleic acids and proteins, or alternatively limit host growth and thus indirectly limit metabolic pathways necessary for viral replication. In order to compare direct and indirect effects of nutrient limitation on virus production within hosts, we manipulated soil nitrogen (N) and phosphorus (P) availability in a glasshouse for the wild grass host Bromus hordeaceus and the viral pathogen Barley yellow dwarf virus-PAV. We found that soil N additions increased viral concentrations within host tissues, and the effect was mediated by host growth. Specifically, in statistical models evaluating the roles of host biomass production, leaf N and leaf P, viral production depended most strongly on host biomass, rather than the concentration of either nutrient. Furthermore, at low soil N, larger plants supported greater viral concentrations than smaller ones, whereas at high N, smaller plants supported greater viral concentrations. Our results suggest that enhanced viral productivity under N enrichment is an indirect consequence of nutrient stimulation to host growth rate. Heightened pathogen production in plants has important implications for a world facing increasing rates of nutrient deposition. PMID:25782030

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

    PubMed Central

    Kumar, Anil; Silverstein, Peter S.

    2014-01-01

    This meeting was a special symposium sponsored by the American Society for Biochemistry and Molecular Biology. The conference was held in Gangzhou, China on July 24–26, 2011 and shared a venue with the Society of Chinese Bioscientists in America (SCBA) Thirteenth International Symposium. Over 150 participants from the Americas, Europe, Asia and Australia attended the meeting. The meeting report 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-kB regulation of viral gene expression. PMID:22029515

  5. 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...

  6. 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

  7. 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

  8. 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

  9. Genomic sequencing, discovery, and characterization of viral pathogens in Glassy-winged Sharpshooters (Homalodisca vitripennis: Hemiptera: Cicadellidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A new viral pathogen, HoCV-1, discovered in the glassy-winged sharpshooter, GWSS, (Homalodisca vitripennis, aka H. coagulata) was examined for the mode of entry into the leafhopper. Few viral pathogens of leafhoppers have been discovered which have potential for use as a biological control agent. To...

  10. Viral infections in atopic dermatitis: pathogenic aspects and clinical management.

    PubMed

    Wollenberg, Andreas; Wetzel, Stefanie; Burgdorf, Walter H C; Haas, Jürgen

    2003-10-01

    A number of different widespread and disseminated viral infections can occur in patients with atopic dermatitis. Eczema molluscatum is troublesome but not dangerous. Although eczema vaccinatum is rare, it is life-threatening and of increased concern as smallpox vaccinations are reintroduced as a response to possible bioterrorism. There is little information on the course of smallpox itself in atopic dermatitis. Eczema herpeticum is the most common member of this group; recent advances in understanding its pathogenesis might contribute to a more successful management of this serious complication. PMID:14564342

  11. Extraction of total nucleic acids from ticks for the detection of bacterial and viral pathogens.

    PubMed

    Crowder, Chris D; Rounds, Megan A; Phillipson, Curtis A; Picuri, John M; Matthews, Heather E; Halverson, Justina; Schutzer, Steven E; Ecker, David J; Eshoo, Mark W

    2010-01-01

    Ticks harbor numerous bacterial, protozoal, and viral pathogens that can cause serious infections in humans and domestic animals. Active surveillance of the tick vector can provide insight into the frequency and distribution of important pathogens in the environment. Nucleic-acid based detection of tick-borne bacterial, protozoan, and viral pathogens requires the extraction of both DNA and RNA (total nucleic acids) from ticks. Traditional methods for nucleic acid extraction are limited to extraction of either DNA or the RNA from a sample. Here we present a simple bead-beating based protocol for extraction of DNA and RNA from a single tick and show detection of Borrelia burgdorferi and Powassan virus from individual, infected Ixodes scapularis ticks. We determined expected yields for total nucleic acids by this protocol for a variety of adult tick species. The method is applicable to a variety of arthropod vectors, including fleas and mosquitoes, and was partially automated on a liquid handling robot. PMID:20180313

  12. A de novo Assembly of the Common Frog (Rana temporaria) Transcriptome and Comparison of Transcription Following Exposure to Ranavirus and Batrachochytrium dendrobatidis

    PubMed Central

    Price, Stephen J.; Garner, Trenton W. J.; Balloux, Francois; Ruis, Chris; Paszkiewicz, Konrad H.; Moore, Karen; Griffiths, Amber G. F.

    2015-01-01

    Amphibians are experiencing global declines and extinctions, with infectious diseases representing a major factor. In this study we examined the transcriptional response of metamorphic hosts (common frog, Rana temporaria) to the two most important amphibian pathogens: Batrachochytrium dendrobatidis (Bd) and Ranavirus. We found strong up-regulation of a gene involved in the adaptive immune response (AP4S1) at four days post-exposure to both pathogens. We detected a significant transcriptional response to Bd, covering the immune response (innate and adaptive immunity, complement activation, and general inflammatory responses), but relatively little transcriptional response to Ranavirus. This may reflect the higher mortality rates found in wild common frogs infected with Ranavirus as opposed to Bd. These data provide a valuable genomic resource for the amphibians, contribute insight into gene expression changes after pathogen exposure, and suggest potential candidate genes for future host-pathogen research. PMID:26111016

  13. 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

  14. 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

  15. 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

  16. Metagenomic approaches to disclose disease-associated pathogens: detection of viral pathogens in honeybees.

    PubMed

    Granberg, Fredrik; Karlsson, Oskar E; Belák, Sándor

    2015-01-01

    Metagenomic approaches have become invaluable for culture-independent and sequence-independent detection and characterization of disease-associated pathogens. Here, the sequential steps from sampling to verification of results are described for a metagenomic-based approach to detect potential pathogens in honeybees. The pre-sequencing steps are given in detail, but due to the rapid development of sequencing technologies, all platform-specific procedures, as well as subsequent bioinformatics analysis, are more generally described. It should also be noted that this approach could, with minor modifications, be adapted for other organisms and sample matrices. PMID:25399116

  17. 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

  18. The role of C5a in acute lung injury induced by highly pathogenic viral infections.

    PubMed

    Wang, Renxi; Xiao, He; Guo, Renfeng; Li, Yan; Shen, Beifen

    2015-05-01

    The complement system, an important part of innate immunity, plays a critical role in pathogen clearance. Unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by highly pathogenic virus including influenza A viruses H5N1, H7N9, and severe acute respiratory syndrome (SARS) coronavirus. In highly pathogenic virus-induced acute lung diseases, high levels of chemotactic and anaphylatoxic C5a were produced as a result of excessive complement activaiton. Overproduced C5a displays powerful biological activities in activation of phagocytic cells, generation of oxidants, and inflammatory sequelae named "cytokine storm", and so on. Blockade of C5a signaling have been implicated in the treatment of ALI induced by highly pathogenic virus. Herein, we review the literature that links C5a and ALI, and review our understanding of the mechanisms by which C5a affects ALI during highly pathogenic viral infection. In particular, we discuss the potential of the blockade of C5a signaling to treat ALI induced by highly pathogenic viruses. PMID:26060601

  19. The role of C5a in acute lung injury induced by highly pathogenic viral infections

    PubMed Central

    Wang, Renxi; Xiao, He; Guo, Renfeng; Li, Yan; Shen, Beifen

    2015-01-01

    The complement system, an important part of innate immunity, plays a critical role in pathogen clearance. Unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by highly pathogenic virus including influenza A viruses H5N1, H7N9, and severe acute respiratory syndrome (SARS) coronavirus. In highly pathogenic virus-induced acute lung diseases, high levels of chemotactic and anaphylatoxic C5a were produced as a result of excessive complement activaiton. Overproduced C5a displays powerful biological activities in activation of phagocytic cells, generation of oxidants, and inflammatory sequelae named “cytokine storm”, and so on. Blockade of C5a signaling have been implicated in the treatment of ALI induced by highly pathogenic virus. Herein, we review the literature that links C5a and ALI, and review our understanding of the mechanisms by which C5a affects ALI during highly pathogenic viral infection. In particular, we discuss the potential of the blockade of C5a signaling to treat ALI induced by highly pathogenic viruses.

  20. Rapid Response to Evaluate the Presence of Amphibian Chytrid Fungus (Batrachochytrium dendrobatidis) and Ranavirus in Wild Amphibian Populations in Madagascar

    PubMed Central

    Kolby, Jonathan E.; Smith, Kristine M.; Ramirez, Sara D.; Rabemananjara, Falitiana; Pessier, Allan P.; Brunner, Jesse L.; Goldberg, Caren S.; Berger, Lee; Skerratt, Lee F.

    2015-01-01

    We performed a rapid response investigation to evaluate the presence and distribution of amphibian pathogens in Madagascar following our identification of amphibian chytrid fungus (Batrachochytrium dendrobatidis, Bd) and ranavirus in commercially exported amphibians. This targeted risk-based field surveillance program was conducted from February to April 2014 encompassing 12 regions and 47 survey sites. We simultaneously collected amphibian and environmental samples to increase survey sensitivity and performed sampling both in wilderness areas and commercial amphibian trade facilities. Bd was not detected in any of 508 amphibian skin swabs or 68 water filter samples, suggesting pathogen prevalence was below 0.8%, with 95% confidence during our visit. Ranavirus was detected in 5 of 97 amphibians, including one adult Mantidactylus cowanii and three unidentified larvae from Ranomafana National Park, and one adult Mantidactylus mocquardi from Ankaratra. Ranavirus was also detected in water samples collected from two commercial amphibian export facilities. We also provide the first report of an amphibian mass-mortality event observed in wild amphibians in Madagascar. Although neither Bd nor ranavirus appeared widespread in Madagascar during this investigation, additional health surveys are required to disentangle potential seasonal variations in pathogen abundance and detectability from actual changes in pathogen distribution and rates of spread. Accordingly, our results should be conservatively interpreted until a comparable survey effort during winter months has been performed. It is imperative that biosecurity practices be immediately adopted to limit the unintentional increased spread of disease through the movement of contaminated equipment or direct disposal of contaminated material from wildlife trade facilities. The presence of potentially introduced strains of ranaviruses suggests that Madagascar's reptile species might also be threatened by disease. Standardized population monitoring of key amphibian and reptile species should be established with urgency to enable early detection of potential impacts of disease emergence in this global biodiversity hotspot. PMID:26083349

  1. 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

  2. Clinical differences between respiratory viral and bacterial mono- and dual pathogen detected among Singapore military servicemen with febrile respiratory illness

    PubMed Central

    Ho, Zheng Jie Marc; Zhao, Xiahong; Cook, Alex R; Loh, Jin Phang; Ng, Sock Hoon; Tan, Boon Huan; Lee, Vernon J

    2015-01-01

    Background Although it is known that febrile respiratory illnesses (FRI) may be caused by multiple respiratory pathogens, there are no population-level studies describing its impact on clinical disease. Methods Between May 2009 and October 2012, 7733 FRI patients and controls in the Singapore military had clinical data and nasal wash samples collected prospectively and sent for PCR testing. Patients with one pathogen detected (mono-pathogen) were compared with those with two pathogens (dual pathogen) for differences in basic demographics and clinical presentation. Results In total, 45.8% had one pathogen detected, 20.2% had two pathogens detected, 30.9% had no pathogens detected, and 3.1% had more than two pathogens. Multiple pathogens were associated with recruits, those with asthma and non-smokers. Influenza A (80.0%), influenza B (73.0%) and mycoplasma (70.6%) were most commonly associated with mono-infections, while adenovirus was most commonly associated with dual infections (62.9%). Influenza A paired with S. pneumoniae had higher proportions of chills and rigors than their respective mono-pathogens (P = 0.03, P = 0.009). H. influenzae paired with either enterovirus or parainfluenzae had higher proportions of cough with phlegm than their respective mono-pathogens. Although there were observed differences in mean proportions of body temperature, nasal symptoms, sore throat, body aches and joint pains between viral and bacterial mono-pathogens, there were few differences between distinct dual-pathogen pairs and their respective mono-pathogen counterparts. Conclusion A substantial number of FRI patients have multiple pathogens detected. Observed clinical differences between patients of dual pathogen and mono-pathogen indicate the likely presence of complex microbial interactions between the various pathogens. PMID:25827870

  3. 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

  4. Biotic factors contributing to theBiotic factors contributing to the emergence of ranavirus in Northemergence of ranavirus in North

    E-print Network

    Gray, Matthew

    -permanent habitats ­ Narrow range distributions ­ Rapid development #12;11/2/2011 4 Chapter I: Objectives 1. Test of ranavirus in Northemergence of ranavirus in North American amphibian communitiesAmerican amphibian. Balseiro Amphibians in DistressAmphibians in Distress · IUCN Red List (IUCN 2011) ­ 12% birds ­ 23% mammals

  5. 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

  6. Assay platforms for the rapid detection of viral pathogens by the ultrahigh sensitivity monitoring of antigen-antibody binding

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The drive for early disease detection and growing threat of bioterrorism has markedly amplified the demand for ultrasensitive, high-speed diagnostic tests for viral pathogens. This presentation describes innovations in the development of platforms and readout methodologies that potentially address d...

  7. Structured literature review of responses of cattle to viral and bacterial pathogens causing bovine respiratory disease complex.

    PubMed

    Grissett, G P; White, B J; Larson, R L

    2015-05-01

    Bovine respiratory disease (BRD) is an economically important disease of cattle and continues to be an intensely studied topic. However, literature summarizing the time between pathogen exposure and clinical signs, shedding, and seroconversion is minimal. A structured literature review of the published literature was performed to determine cattle responses (time from pathogen exposure to clinical signs, shedding, and seroconversion) in challenge models using common BRD viral and bacterial pathogens. After review a descriptive analysis of published studies using common BRD pathogen challenge studies was performed. Inclusion criteria were single pathogen challenge studies with no treatment or vaccination evaluating outcomes of interest: clinical signs, shedding, and seroconversion. Pathogens of interest included: bovine viral diarrhea virus (BVDV), bovine herpesvirus type 1 (BHV-1), parainfluenza-3 virus, bovine respiratory syncytial virus, Mannheimia haemolytica, Mycoplasma bovis, Pastuerella multocida, and Histophilus somni. Thirty-five studies and 64 trials were included for analysis. The median days to the resolution of clinical signs after BVDV challenge was 15 and shedding was not detected on day 12 postchallenge. Resolution of BHV-1 shedding resolved on day 12 and clinical signs on day 12 postchallenge. Bovine respiratory syncytial virus ceased shedding on day 9 and median time to resolution of clinical signs was on day 12 postchallenge. M. haemolytica resolved clinical signs 8 days postchallenge. This literature review and descriptive analysis can serve as a resource to assist in designing challenge model studies and potentially aid in estimation of duration of clinical disease and shedding after natural pathogen exposure. PMID:25929158

  8. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees

    PubMed Central

    Di Prisco, Gennaro; Cavaliere, Valeria; Annoscia, Desiderato; Varricchio, Paola; Caprio, Emilio; Nazzi, Francesco; Gargiulo, Giuseppe; Pennacchio, Francesco

    2013-01-01

    Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-?B immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-?B activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-?B signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture. PMID:24145453

  9. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees.

    PubMed

    Di Prisco, Gennaro; Cavaliere, Valeria; Annoscia, Desiderato; Varricchio, Paola; Caprio, Emilio; Nazzi, Francesco; Gargiulo, Giuseppe; Pennacchio, Francesco

    2013-11-12

    Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-?B immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-?B activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-?B signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture. PMID:24145453

  10. Prevalence of and risk factors associated with viral and bacterial pathogens in farmed European wild boar.

    PubMed

    Hälli, Outi; Ala-Kurikka, Eve; Nokireki, Tiina; Skrzypczak, Teresa; Raunio-Saarnisto, Mirja; Peltoniemi, Olli A T; Heinonen, Mari

    2012-10-01

    The aim of this study was to estimate in farmed European wild boars the prevalence of and risk factors associated with a range of common porcine viral and bacterial infections, namely, porcine parvovirus (PPV), porcine circovirus type 2 (PCV2), swine influenza virus (SIV), Aujeszky's disease virus (ADV), classical swine fever virus (CSFV), swine vesicular disease virus (SVDV), coronavirus causing transmissible gastroenteritis (TGEV), porcine reproductive and respiratory syndrome virus (PRRSV), Mycoplasma hyopneumoniae, Lawsonia intracellularis, Brucella spp., and Leptospira spp. A sampling frame was compiled based on a national record of wild boar farmers, and 32 farms were surveyed. Serological screening was carried out on 303 samples from animals slaughtered between 2005 and 2008, and random-effect logistic regression models were developed for pathogens with a 'non-zero' prevalence. The apparent animal prevalence for PPV, PCV2, and L. intracellularis was 46.5% (95% confidence interval [CI] 41-52%), 51.1% (95% CI 45-57%) and 59.2% (95% CI 54-65%), respectively. Apparent farm seroprevalence rates for PPV, PCV2 and Lawsonia intracellularis were 56.3% (95% CI, 39-73%), 21.9% (95% CI, 8-36%) and 78.1% (95% CI, 64-92%), respectively. No antibodies were detected against SIV, ADV, CSFV, SVDV, TGEV, PRSSV, Leptospira spp., Brucella spp., or M. hyopneumoniae. Increasing herd size, proximity to dense populations of domestic swine and later sampling times within the survey period were found to be risk factors. Overall, the seroprevalence of these pathogens in farmed wild boar was similar to that in the farmed domestic pig population in Finland. However, it is possible that the rearing of wild boars in fenced estates may predispose them to particular infections, as reflected in higher antibody titres. PMID:22516920

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

    E-print Network

    Gray, Matthew

    asymmetry and ranavirus infection are positively correlated (L. clamitans) StAmour et al. (2008) Emerg correlates with disease g Annual variation in the prevalence of ATV & potential environmental covariates

  12. 51www.wildlife.org The Wildlife Society The Rise of Ranavirus

    E-print Network

    Gray, Matthew

    or dead infected individuals may also succumb to the disease. After a ranavirus outbreak, aquatic to transform aquatic ecosystems as ranaviruses. Ominous Body of Evidence With one in three amphibian species

  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. Susceptibility of farmed juvenile giant grouper Epinephelus lanceolatus to a newly isolated grouper iridovirus (genus Ranavirus).

    PubMed

    Peng, Chao; Ma, Hongling; Su, Youlu; Wen, Weigeng; Feng, Juan; Guo, Zhixun; Qiu, Lihua

    2015-06-12

    A ranavirus was isolated from the diseased farmed groupers (Grouper iridovirus in genus Ranavirus, GIV-R), Epinephelus hybrids (blotchy rock cod, Epinephelus fuscoguttatus ?×giant grouper, Epinephelus lanceolatus ?), in Sanya, Hainan, in July 2013. In this study, susceptibility of farmed juvenile giant grouper E. lanceolatus to GIV-R was determined by intraperitoneally injection. The cumulative mortality reached to 81% at 5 day post infection. Histologically, severe degeneration with massive pycnotic nuclei in spleen and kidney tissues was observed, and some small-size inclusion body-bearing cells (IBCs) existed in spleen. Hemorrhage and infiltration of inflammatory cells were presented in gill, liver and heart along with tissue degeneration and necrosis of varying severity. The results of immunohistochemistry analysis showed that the strongest immunolabellings were obtained from the kidney and spleen tissues, while intermediate intensity signals were observed in the heart, stomach, gill and liver tissues, and the weakest signals were obtained from the intestine and brain, but no signal was obtained in eyes. Electron microscopy revealed that spleen of moribund fish contained many viral particles in cytoplasm. Interestingly, in surviving fish, abnormal hypertrophic cells were observed in both splenic corpuscle and renal corpuscle, while no hypertrophic cell was observed in the other parts of spleen and kidney tissues. Moreover, immunolabellings only stained the hypertrophic cells in splenic corpuscle and renal corpuscle. This indicated that splenic corpuscle and renal corpuscle play an important role in GIV-R infection and replication. PMID:25912024

  15. Prevalence of swine viral and bacterial pathogens in rodents and stray cats captured around pig farms in Korea.

    PubMed

    Truong, Quang Lam; Seo, Tae Won; Yoon, Byung-Il; Kim, Hyeon-Cheol; Han, Jeong Hee; Hahn, Tae-Wook

    2013-12-30

    In 2008, 102 rodents and 24 stray cats from the areas around 9 pig farms in northeast South Korea were used to determine the prevalence of the following selected swine pathogens: ten viral pathogens [porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), rotavirus, classical swine fever virus (CSFV), porcine circovirus type 2 (PCV2), encephalomyocarditis virus (EMCV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine parvovirus (PPV), pseudorabies virus (PRV) and Japanese encephalitis virus (JEV)] and four bacterial pathogens (Brucella, Leptospira, Salmonella and Lawsonia intracellularis). In total, 1,260 tissue samples from 102 rodents and 24 stray cats were examined by specific PCR and RT-PCR assays, including tissue samples of the brain, tonsils, lungs, heart, liver, kidneys, spleen, small intestine, large intestine and mesenteric lymph nodes. The percentages of PCR-positive rodents for the porcine pathogens were as follows: 63.7% for Leptospira, 39.2% for Brucella, 6.8% for Salmonella, 15.7% for L. intracellularis, 14.7% for PCV2 and 3.9% for EMCV. The percentages of PCR-positive stray cats for the swine pathogens were as follows: 62.5% for Leptospira, 25% for Brucella, 12.5% for Salmonella, 12.5% for L. intracellularis and 4.2% for PEDV. These results may be helpful for developing control measures to prevent the spread of infectious diseases of pigs. PMID:23892461

  16. Prevalence of Swine Viral and Bacterial Pathogens in Rodents and Stray Cats Captured around Pig Farms in Korea

    PubMed Central

    TRUONG, Quang Lam; SEO, Tae Won; YOON, Byung-Il; KIM, Hyeon-Cheol; HAN, Jeong Hee; HAHN, Tae-Wook

    2013-01-01

    ABSTRACT In 2008, 102 rodents and 24 stray cats from the areas around 9 pig farms in northeast South Korea were used to determine the prevalence of the following selected swine pathogens: ten viral pathogens [porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), rotavirus, classical swine fever virus (CSFV), porcine circovirus type 2 (PCV2), encephalomyocarditis virus (EMCV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine parvovirus (PPV), pseudorabies virus (PRV) and Japanese encephalitis virus (JEV)] and four bacterial pathogens (Brucella, Leptospira, Salmonella and Lawsonia intracellularis). In total, 1,260 tissue samples from 102 rodents and 24 stray cats were examined by specific PCR and RT-PCR assays, including tissue samples of the brain, tonsils, lungs, heart, liver, kidneys, spleen, small intestine, large intestine and mesenteric lymph nodes. The percentages of PCR-positive rodents for the porcine pathogens were as follows: 63.7% for Leptospira, 39.2% for Brucella, 6.8% for Salmonella, 15.7% for L. intracellularis, 14.7% for PCV2 and 3.9% for EMCV. The percentages of PCR-positive stray cats for the swine pathogens were as follows: 62.5% for Leptospira, 25% for Brucella, 12.5% for Salmonella, 12.5% for L. intracellularis and 4.2% for PEDV. These results may be helpful for developing control measures to prevent the spread of infectious diseases of pigs. PMID:23892461

  17. Ranavirus infections associated with skin lesions in lizards

    PubMed Central

    2013-01-01

    Ranaviral disease in amphibians has been studied intensely during the last decade, as associated mass-mortality events are considered to be a global threat to wild animal populations. Several studies have also included other susceptible ectothermic vertebrates (fish and reptiles), but only very few cases of ranavirus infections in lizards have been previously detected. In this study, we focused on clinically suspicious lizards and tested these animals for the presence of ranaviruses. Virological screening of samples from lizards with increased mortality and skin lesions over a course of four years led to the detection of ranaviral infections in seven different groups. Affected species were: brown anoles (Anolis sagrei), Asian glass lizards (Dopasia gracilis), green anoles (Anolis carolinensis), green iguanas (Iguana iguana), and a central bearded dragon (Pogona vitticeps). Purulent to ulcerative-necrotizing dermatitis and hyperkeratosis were diagnosed in pathological examinations. All animals tested positive for the presence of ranavirus by PCR and a part of the major capsid protein (MCP) gene of each virus was sequenced. Three different ranaviruses were isolated in cell culture. The analyzed portions of the MCP gene from each of the five different viruses detected were distinct from one another and were 98.4-100% identical to the corresponding portion of the frog virus 3 (FV3) genome. This is the first description of ranavirus infections in these five lizard species. The similarity in the pathological lesions observed in these different cases indicates that ranaviral infection may be an important differential diagnosis for skin lesions in lizards. PMID:24073785

  18. Ranavirus infections associated with skin lesions in lizards.

    PubMed

    Stöhr, Anke C; Blahak, Silvia; Heckers, Kim O; Wiechert, Jutta; Behncke, Helge; Mathes, Karina; Günther, Pascale; Zwart, Peer; Ball, Inna; Rüschoff, Birgit; Marschang, Rachel E

    2013-01-01

    Ranaviral disease in amphibians has been studied intensely during the last decade, as associated mass-mortality events are considered to be a global threat to wild animal populations. Several studies have also included other susceptible ectothermic vertebrates (fish and reptiles), but only very few cases of ranavirus infections in lizards have been previously detected. In this study, we focused on clinically suspicious lizards and tested these animals for the presence of ranaviruses. Virological screening of samples from lizards with increased mortality and skin lesions over a course of four years led to the detection of ranaviral infections in seven different groups. Affected species were: brown anoles (Anolis sagrei), Asian glass lizards (Dopasia gracilis), green anoles (Anolis carolinensis), green iguanas (Iguana iguana), and a central bearded dragon (Pogona vitticeps). Purulent to ulcerative-necrotizing dermatitis and hyperkeratosis were diagnosed in pathological examinations. All animals tested positive for the presence of ranavirus by PCR and a part of the major capsid protein (MCP) gene of each virus was sequenced. Three different ranaviruses were isolated in cell culture. The analyzed portions of the MCP gene from each of the five different viruses detected were distinct from one another and were 98.4-100% identical to the corresponding portion of the frog virus 3 (FV3) genome. This is the first description of ranavirus infections in these five lizard species. The similarity in the pathological lesions observed in these different cases indicates that ranaviral infection may be an important differential diagnosis for skin lesions in lizards. PMID:24073785

  19. [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

  20. 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....

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

    E-print Network

    Pugh, Roberta Ann

    1979-01-01

    with tendon material from VAV-IBDV treated chickens. . . . . . . . . . . . . . . . . . . . . . . 42 INTRODUCTION Viral arthritis (VA) is a widespread reovirus infection of chickens characterized by the involvement of synovial membranes, tendon sheaths... characterized the West Virginia isolate of viral arthrit1s virus (VAV) as a reovirus. Other workers have confirmed their character1zat1on of the virus (38, 59). Reoviruses have been isolated from the respiratory and diges- t1ve tracts of chickens and turkeys...

  2. Rapid detection and identification of viral and bacterial fish pathogens using a DNA array-based multiplex assay.

    PubMed

    Lievens, B; Frans, I; Heusdens, C; Justé, A; Jonstrup, S P; Lieffrig, F; Willems, K A

    2011-11-01

    Fish diseases can be caused by a variety of diverse organisms, including bacteria, fungi, viruses and protozoa, and pose a universal threat to the ornamental fish industry and aquaculture. The lack of rapid, accurate and reliable means by which fish pathogens can be detected and identified has been one of the main limitations in fish pathogen diagnosis and fish disease management and has consequently stimulated the search for alternative diagnostic techniques. Here, we describe a method based on multiplex and broad-range PCR amplification combined with DNA array hybridization for the simultaneous detection and identification of all cyprinid herpesviruses (CyHV-1, CyHV-2 and CyHV-3) and some of the most important fish pathogenic Flavobacterium species, including F. branchiophilum, F. columnare and F. psychrophilum. For virus identification, the DNA polymerase and helicase genes were targeted. For bacterial identification, the ribosomal RNA gene was used. The developed methodology permitted 100% specificity for the identification of the target species. Detection sensitivity was equivalent to 10 viral genomes or less than a picogram of bacterial DNA. The utility and power of the array for sensitive pathogen detection and identification in complex samples such as infected tissue is demonstrated in this study. PMID:21988358

  3. The Survival of Bacterial and Viral Pathogens in Manure and Biosolids in the Southeastern United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study aims to determine the survival of bacterial pathogens after the application of fecal derived fertilizer sources such as municipal biosolids or manure. The purpose is to elucidate the effect of fecal source on the prolonged viability of pathogens in soil. Soils will be applied and incorp...

  4. Transcriptome analysis of Frog Virus 3, the type species of the genus Ranavirus, family Iridoviridae

    PubMed Central

    Majji, S.; Thodima, V.; Sample, R.; Whitley, D.; Deng, Y.; Mao, J.; Chinchar, V. G.

    2009-01-01

    Frog virus 3 is the best characterized species within the genus Ranavirus, family Iridoviridae. FV3's large (?105 kbp) dsDNA genome encodes 98 putative open reading frames (ORFs) that are expressed in a coordinated fashion leading to the sequential appearance of immediate early (IE), delayed early (DE) and late (L) viral transcripts. As a step toward elucidating molecular events in FV3 replication, we sought to identify the temporal class of viral messages. To accomplish this objective an oligonucleotide microarray containing 70-mer probes corresponding to each of the 98 FV3 ORFs was designed and used to examine viral gene expression. Viral transcription was initially monitored during the course of a productive replication cycle at 2, 4 and 9 hours after infection. To confirm results of the time course assay, viral gene expression was also monitored in the presence of cycloheximide (CHX), which limits expression to only IE genes, and following infection with a temperature sensitive (ts) mutant which at non-permissive temperatures is defective in viral DNA synthesis and blocked in late gene expression. Subsequently, microarray analyses were validated by RT-PCR and qRT-PCR. Using these approaches we identified 33 IE genes, 22 DE genes and 36 L viral genes. The temporal class of the 7 remaining genes could not be determined. Comparison of putative protein function with temporal class indicated that, in general, genes encoding putative regulatory factors, or proteins that played a part in nucleic acid metabolism and immune evasion, were classified as IE and DE genes, whereas those involved in DNA packaging and virion assembly were considered L genes. Information on temporal class will provide the basis for determining whether members of the same temporal class contain common upstream regulatory regions and perhaps allow us to identify virion-associated and virus-induced proteins that control viral gene expression. PMID:19608212

  5. 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

  6. 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

  7. 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

    2015-01-01

    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

  8. 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

  9. 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.

  10. Widespread Occurrence of Ranavirus in Pond-Breeding Amphibian Populations

    E-print Network

    Gray, Matthew

    populations, yet their distribution in amphibian communities and the association of infection with possible practices that reduce the water quality of amphibian breeding habitats (e.g., cattle access to wetlands of data regarding the distribution of ranaviruses in wild amphibian populations has come from sites

  11. Ranaviruses: Not Just for Frogs V. Gregory Chinchar1

    E-print Network

    Gray, Matthew

    , or budding from the plasma membrane (Figure 1). Although the outlines of ranavirus replication are known serendipitously during an attempt to generate frog kidney cell cultures for the propagation of Lucke herpesvirus for humans or commercially important animals, were not, as originally thought, oncogenic, and did not appear

  12. Viral proteins and Src family kinases: Mechanisms of pathogenicity from a “liaison dangereuse”

    PubMed Central

    Pagano, Mario Angelo; Tibaldi, Elena; Palù, Giorgio; Brunati, Anna Maria

    2013-01-01

    To complete their life cycle and spread, viruses interfere with and gain control of diverse cellular processes, this most often occurring through interaction between viral proteins (VPs) and resident protein partners. Among the latter, Src family kinases (SFKs), a class of non-receptor tyrosine kinases that contributes to the conversion of extracellular signals into intracellular signaling cascades and is involved in virtually all cellular processes, have recently emerged as critical mediators between the cell’s infrastructure and the viral demands. In this scenario, structural or ex novo synthesized VPs are able to bind to the different domains of these enzymes through specific short linear motifs present along their sequences. Proline-rich motifs displaying the conserved minimal consensus PxxP and recognizing the SFK Src homology (SH)3 domain constitute a cardinal signature for the formation of multiprotein complexes and this interaction may promote phosphorylation of VPs by SFKs, thus creating phosphotyrosine motifs that become a docking site for the SH2 domains of SFKs or other SH2 domain-bearing signaling molecules. Importantly, the formation of these assemblies also results in a change in the activity and/or location of SFKs, and these events are critical in perturbing key signaling pathways so that viruses can utilize the cell’s machinery to their own benefit. In the light of these observations, although VPs as such, especially those with enzyme activity, are still regarded as valuable targets for therapeutic strategies, multiprotein complexes composed of viral and host cell proteins are increasingly becoming objects of investigation with a view to deeply characterize the structural aspects that favor their formation and to develop new compounds able to contrast viral diseases in an alternative manner. PMID:24175231

  13. The Murine Cytomegalovirus Chemokine Homolog, m131\\/129, Is a Determinant of Viral Pathogenicity

    Microsoft Academic Search

    PETER FLEMING; NICHOLAS DAVIS-POYNTER; MARIAPIA DEGLI-ESPOSTI; ELOISE DENSLEY; JOHN PAPADIMITRIOU; GEOFFREY SHELLAM; HELEN FARRELL

    1999-01-01

    Chemokines are important mediators of the early inflammatory response to infection and modify a wide range of host immune responses. Functional homologs of cellular chemokines have been identified in a number of herpesviruses, suggesting that the subversion of the host chemokine response contributes to the pathogen- esis of these viruses. Transcriptional and reverse transcription-PCR analyses demonstrated that the murine cytomegalovirus

  14. 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...

  15. 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...

  16. Feral swine exposure to selected viral and bacterial pathogens in southern Texas

    Microsoft Academic Search

    Tyler A. Campbell; Randy W. DeYoung; Erin M. Wehland; Lon I. Grassman; David B. Long; Johanna Delgado-Acevedo

    2008-01-01

    Summary Blood samples were obtained from feral swine in Texas to determine the seropreva- lence of selected pathogens. Exposures rates were 35%, 1%, and 1% for pseudorabies virus, Brucella, and porcine reproductive and respiratory syndrome virus, respec- tively. Simple modifications to enclosures may provide adequate biosecurity for swine at risk within this region.

  17. SEWAGE SLUDGE VIRAL AND PATHOGENIC AGENTS IN SOIL-PLANT-ANIMAL SYSTEMS

    EPA Science Inventory

    A multidisciplinary study was carried out to determine the ultimate fate of various toxic elements or pathogens associated with Florida and Chicago municipal sludges when applied to soil-plant-water systems and to determine physiologic, pathologic, growth, and reproductive respon...

  18. 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

  19. Bacterial and viral pathogens in live oysters: 2007 United States market survey.

    PubMed

    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

    2010-05-01

    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

  20. 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

  1. 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

    2015-02-01

    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

  2. Canine enteric coronaviruses: emerging viral pathogens with distinct recombinant spike proteins.

    PubMed

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

    2014-08-01

    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

  3. 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

  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. 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.

  6. RNA aptamers inhibit the growth of the fish pathogen viral hemorrhagic septicemia virus (VHSV).

    PubMed

    Punnarak, Porntep; Santos, Mudjekeewis D; Hwang, Seong Don; Kondo, Hidehiro; Hirono, Ikuo; Kikuchi, Yo; Aoki, Takashi

    2012-12-01

    Viral hemorrhagic septicemia virus (VHSV) is a serious disease impacting wild and cultured fish worldwide. Hence, an effective therapeutic method against VHSV infection needs to be developed. Aptamer technology is a new and promising method for diagnostics and therapeutics. It revolves around the use of an aptamer molecule, an artificial ligand (nucleic acid or protein), which has the capacity to recognize target molecules with high affinity and specificity. Here, we aimed at selecting RNA aptamers that can specifically bind to and inhibit the growth of a strain of fish VHSV both in vitro and in vivo. Three VHSV-specific RNA aptamers (F1, F2, and C6) were selected from a pool of artificially and randomly produced oligonucleotides using systematic evolution of ligands by exponential enrichment. The three RNA aptamers showed obvious binding to VHSV in an electrophoretic mobility shift assay but not to other tested viruses. The RNA aptamers were tested for their ability to inhibit VHSV in vitro using hirame natural embryo (HINAE) cells. Cytopathic effect and plaque assays showed that all aptamers inhibited the growth of VHSV in HINAE cells. In vivo tests using RNA aptamers produced by Rhodovulum sulfidophilum showed that extracellular RNA aptamers inhibited VHSV infection in Japanese flounder. These results suggest that the RNA aptamers are a useful tool for protection against VHSV infection in Japanese flounder. PMID:22527269

  7. Direct Metagenomic Detection of Viral Pathogens in Nasal and Fecal Specimens Using an Unbiased High-Throughput Sequencing Approach

    PubMed Central

    Sakon, Naomi; Ueda, Mayo; Tougan, Takahiro; Yamashita, Akifumi; Goto, Naohisa; Takahashi, Kazuo; Yasunaga, Teruo; Ikuta, Kazuyoshi; Mizutani, Tetsuya; Okamoto, Yoshiko; Tagami, Michihira; Morita, Ryoji; Maeda, Norihiro; Kawai, Jun; Hayashizaki, Yoshihide; Nagai, Yoshiyuki; Horii, Toshihiro; Iida, Tetsuya; Nakaya, Takaaki

    2009-01-01

    With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a “next-generation” parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1–0.25 ml of nasopharyngeal aspirates (N?=?3) and fecal specimens (N?=?5), and more than 10 µg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298–32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome–derived, 20–460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484–15,260 reads of norovirus sequence (78–98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures. PMID:19156205

  8. Direct metagenomic detection of viral pathogens in nasal and fecal specimens using an unbiased high-throughput sequencing approach.

    PubMed

    Nakamura, Shota; Yang, Cheng-Song; Sakon, Naomi; Ueda, Mayo; Tougan, Takahiro; Yamashita, Akifumi; Goto, Naohisa; Takahashi, Kazuo; Yasunaga, Teruo; Ikuta, Kazuyoshi; Mizutani, Tetsuya; Okamoto, Yoshiko; Tagami, Michihira; Morita, Ryoji; Maeda, Norihiro; Kawai, Jun; Hayashizaki, Yoshihide; Nagai, Yoshiyuki; Horii, Toshihiro; Iida, Tetsuya; Nakaya, Takaaki

    2009-01-01

    With the severe acute respiratory syndrome epidemic of 2003 and renewed attention on avian influenza viral pandemics, new surveillance systems are needed for the earlier detection of emerging infectious diseases. We applied a "next-generation" parallel sequencing platform for viral detection in nasopharyngeal and fecal samples collected during seasonal influenza virus (Flu) infections and norovirus outbreaks from 2005 to 2007 in Osaka, Japan. Random RT-PCR was performed to amplify RNA extracted from 0.1-0.25 ml of nasopharyngeal aspirates (N = 3) and fecal specimens (N = 5), and more than 10 microg of cDNA was synthesized. Unbiased high-throughput sequencing of these 8 samples yielded 15,298-32,335 (average 24,738) reads in a single 7.5 h run. In nasopharyngeal samples, although whole genome analysis was not available because the majority (>90%) of reads were host genome-derived, 20-460 Flu-reads were detected, which was sufficient for subtype identification. In fecal samples, bacteria and host cells were removed by centrifugation, resulting in gain of 484-15,260 reads of norovirus sequence (78-98% of the whole genome was covered), except for one specimen that was under-detectable by RT-PCR. These results suggest that our unbiased high-throughput sequencing approach is useful for directly detecting pathogenic viruses without advance genetic information. Although its cost and technological availability make it unlikely that this system will very soon be the diagnostic standard worldwide, this system could be useful for the earlier discovery of novel emerging viruses and bioterrorism, which are difficult to detect with conventional procedures. PMID:19156205

  9. A sodium channel variant in Aedes aegypti as a candidate pathogen sensor for viral-associated molecular patterns.

    PubMed

    Lee, Cara; Jones, Alexis; Kainz, Danielle; Khan, Faatima; Carrithers, Michael D

    2015-08-01

    Recent work demonstrated that a splice variant of a human macrophage voltage-gated sodium channel expressed on endosomes acts as an intracellular sensor for dsRNA, a viral-associated molecular pattern. Here our goal was to identify a candidate gene in a clinically relevant invertebrate model with related cellular and pattern recognition properties. The para gene in drosophila and other insects encodes voltage-gated sodium channels with similar electrophysiological properties to those found in vertebrate excitable membranes. A database search revealed that the AAEL006019 gene in Aedes aegypti, the yellow fever mosquito, encodes a voltage-gated sodium channel that is distinct from genes that encode para-like sodium channels. As compared to para-like channels, the protein products from this gene have deletions in the N-terminus and in the DII-DIII linker region. When over-expressed in an Aedes aegypti cell line, CCL-125, the AAEL006019 channel demonstrated cytoplasmic expression on vesicular-like organelles. Electrophysiologic analysis revealed that the channel mediates small inward currents that are enhanced by synthetic mimics of viral-derived ssRNA, R848 and ORN02, but not the dsRNA mimic, poly I:C. R848 treatment of CCL-125 cells that express high levels of the channels led to increased expression of RelA and Ago2, two mediators of insect innate immunity. These results suggest that the AAEL006019 channel acts as an intracellular pathogen sensor for ssRNA molecular patterns. PMID:26086103

  10. Application of FTA technology for sampling, recovery and molecular characterization of viral pathogens and virus-derived transgenes from plant tissues

    PubMed Central

    Ndunguru, Joseph; Taylor, Nigel J; Yadav, Jitender; Aly, Haytham; Legg, James P; Aveling, Terry; Thompson, Graham; Fauquet, Claude M

    2005-01-01

    Background Plant viral diseases present major constraints to crop production. Effective sampling of the viruses infecting plants is required to facilitate their molecular study and is essential for the development of crop protection and improvement programs. Retaining integrity of viral pathogens within sampled plant tissues is often a limiting factor in this process, most especially when sample sizes are large and when operating in developing counties and regions remote from laboratory facilities. FTA is a paper-based system designed to fix and store nucleic acids directly from fresh tissues pressed into the treated paper. We report here the use of FTA as an effective technology for sampling and retrieval of DNA and RNA viruses from plant tissues and their subsequent molecular analysis. Results DNA and RNA viruses were successfully recovered from leaf tissues of maize, cassava, tomato and tobacco pressed into FTA® Classic Cards. Viral nucleic acids eluted from FTA cards were found to be suitable for diagnostic molecular analysis by PCR-based techniques and restriction analysis, and for cloning and nucleotide sequencing in a manner equivalent to that offered by tradition isolation methods. Efficacy of the technology was demonstrated both from sampled greenhouse-grown plants and from leaf presses taken from crop plants growing in farmer's fields in East Africa. In addition, FTA technology was shown to be suitable for recovery of viral-derived transgene sequences integrated into the plant genome. Conclusion Results demonstrate that FTA is a practical, economical and sensitive method for sampling, storage and retrieval of viral pathogens and plant genomic sequences, when working under controlled conditions and in the field. Application of this technology has the potential to significantly increase ability to bring modern analytical techniques to bear on the viral pathogens infecting crop plants. PMID:15904535

  11. Purification and characterization of a viral chitinase active against plant pathogens and herbivores from transgenic tobacco.

    PubMed

    Di Maro, Antimo; Terracciano, Irma; Sticco, Lucia; Fiandra, Luisa; Ruocco, Michelina; Corrado, Giandomenico; Parente, Augusto; Rao, Rosa

    2010-05-01

    The Autographa californica nucleopolyhedrovirus chitinase A (AcMNPV ChiA) is a chitinolytic enzyme with fungicidal and insecticidal properties. Its expression in transgenic plants enhances resistance against pests and fungal pathogens. We exploited tobacco for the production of a biologically active recombinant AcMNPV ChiA (rChiA), as such species is an alternative to traditional biological systems for large-scale enzyme production. The protein was purified from leaves using ammonium sulfate precipitation followed by anion exchange and gel-filtration chromatography. Transgenic plants produced an estimated 14 mg kg(-1) fresh leaf weight, which represents 0.2% of total soluble proteins. The yield of the purification was about 14% (2 mg kg(-1) fresh leaf weight). The comparison between the biochemical and kinetic properties of the rChiA with those of a commercial Serratia marcescens chitinase A indicated that the rChiA was thermostable and more resistant at basic pH, two positive features for agricultural and industrial applications. Finally, we showed that the purified rChiA enhanced the permeability of the peritrophic membrane of larvae of two Lepidoptera (Bombyx mori and Heliothis virescens) and inhibited spore germination and growth of the phytopatogenic fungus Alternaria alternata. The data indicated that tobacco represents a suitable platform for the production of rChiA, an enzyme with interesting features for future applications as "eco-friendly" control agent in agriculture. PMID:20302895

  12. 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.

  13. Epidemiology of viral pathogens of free-ranging dogs and Indian foxes in a human-dominated landscape in central India.

    PubMed

    Belsare, A V; Vanak, A T; Gompper, M E

    2014-08-01

    There is an increasing concern that free-ranging domestic dog (Canis familiaris) populations may serve as reservoirs of pathogens which may be transmitted to wildlife. We documented the prevalence of antibodies to three viral pathogens, canine parvovirus (CPV), canine distemper virus (CDV) and canine adenovirus (CAV), in free-ranging dog and sympatric Indian fox (Vulpes bengalensis) populations in and around the Great Indian Bustard Wildlife Sanctuary, in Maharashtra, central India. A total of 219 dogs and 33 foxes were sampled during the study period. Ninety-three percentage of dogs and 87% of foxes were exposed to one or more of the three pathogens. Exposure rates in dogs were high: >88% for CPV, >72% for CDV and 71% for CAV. A large proportion of adult dogs had antibodies against these pathogens due to seroconversion following earlier natural infection. The high prevalence of exposure to these pathogens across the sampling sessions, significantly higher exposure rates of adults compared with juveniles, and seroconversion in some unvaccinated dogs documented during the study period suggests that these pathogens are enzootic. The prevalence of exposure to CPV, CDV and CAV in foxes was 48%, 18% and 52%, respectively. Further, a high rate of mortality was documented in foxes with serologic evidence of ongoing CDV infection. Dogs could be playing a role in the maintenance and transmission of these pathogens in the fox population, but our findings show that most dogs in the population are immune to these pathogens by virtue of earlier natural infection, and therefore, these individuals make little current or future contribution to viral maintenance. Vaccination of this cohort will neither greatly improve their collective immune status nor contribute to herd immunity. Our findings have potentially important implications for dog disease control programmes that propose using canine vaccination as a tool for conservation management of wild carnivore populations. PMID:25135467

  14. Viral infection

    PubMed Central

    Puigdomènech, Isabel; de Armas-Rillo, Laura; Machado, José-David

    2011-01-01

    Viruses have developed different survival strategies in host cells by crossing cell-membrane compartments, during different steps of their viral life cycle. In fact, the non-regenerative viral membrane of enveloped viruses needs to encounter the dynamic cell-host membrane, during early steps of the infection process, in which both membranes fuse, either at cell-surface or in an endocytic compartment, to promote viral entry and infection. Once inside the cell, many viruses accomplish their replication process through exploiting or modulating membrane traffic, and generating specialized compartments to assure viral replication, viral budding and spreading, which also serve to evade the immune responses against the pathogen. In this review, we have attempted to present some data that highlight the importance of membrane dynamics during viral entry and replicative processes, in order to understand how viruses use and move through different complex and dynamic cell-membrane structures and how they use them to persist. PMID:21966556

  15. NS Reassortment of an H7-Type Highly Pathogenic Avian Influenza Virus Affects Its Propagation by Altering the Regulation of Viral RNA Production and Antiviral Host Response? †

    PubMed Central

    Wang, Zhongfang; Robb, Nicole C.; Lenz, Eva; Wolff, Thorsten; Fodor, Ervin; Pleschka, Stephan

    2010-01-01

    Highly pathogenic avian influenza viruses (HPAIV) with reassorted NS segments from H5- and H7-type avian virus strains placed in the genetic background of the A/FPV/Rostock/34 HPAIV (FPV; H7N1) were generated by reverse genetics. Virological characterizations demonstrated that the growth kinetics of the reassortant viruses differed from that of wild-type (wt) FPV and depended on whether cells were of mammalian or avian origin. Surprisingly, molecular analysis revealed that the different reassortant NS segments were not only responsible for alterations in the antiviral host response but also affected viral genome replication and transcription as well as nuclear ribonucleoprotein (RNP) export. RNP reconstitution experiments demonstrated that the effects on accumulation levels of viral RNA species were dependent on the specific NS segment as well as on the genetic background of the RNA-dependent RNA polymerase (RdRp). Beta interferon (IFN-?) expression and the induction of apoptosis were found to be inversely correlated with the magnitude of viral growth, while the NS allele, virus subtype, and nonstructural protein NS1 expression levels showed no correlation. Thus, these results demonstrate that the origin of the NS segment can have a dramatic effect on the replication efficiency and host range of HPAIV. Overall, our data suggest that the propagation of NS reassortant influenza viruses is affected at multiple steps of the viral life cycle as a result of the different effects of the NS1 protein on multiple viral and host functions. PMID:20739516

  16. 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

  17. Differences in highly pathogenic avian influenza viral pathogenesis and associated early inflammatory response in chickens and ducks.

    PubMed

    Cornelissen, J B W J; Vervelde, L; Post, J; Rebel, J M J

    2013-08-01

    We studied the immunological responses in the lung, brain and spleen of ducks and chickens within the first 7 days after infection with H7N1 highly pathogenic avian influenza (HPAI). Infection with HPAI caused significant morbidity and mortality in chickens, while in ducks the infection was asymptomatic. The HPAI viral mRNA load was higher in all investigated tissues of chickens compared with duck tissues. In the lung, brain and spleen of HPAI-infected chickens, a high, but delayed, pro-inflammatory response of IL-6 and IL-1? mRNA was induced, including up-regulation of IFN-?, IFN-?, TLR3 and MDA-5 mRNA from 1 day post infection (p.i.). Whereas in ducks already at 8 h p.i., a quicker but lower response was found for IL-6, IL-1? and iNOS mRNA followed by a delayed activation of TLR7, RIG-I, MDA5 and IFN-? mRNA response. Virus-infected areas in the lung of chickens co-localized with KUL-01? (macrophages, dendritic cells), CD4?, and CD8?? cells, during the first day after infection. However, only KUL-01? cells co-localized with the virus after 1 day p.i. In ducks, CVI-ChNL-68.1? (macrophage-like cells), CD4? and CD8?? cells and apoptosis co-localized with the virus within 8 h p.i. Apoptosis was detected in the brain and lung of HPAI-infected chickens after 2 days p.i. and apoptotic cells co-localized with virus-infected areas. In conclusion, excessive delayed cytokine inflammatory responses but inadequate cellular immune responses may contribute to pathogenesis in chickens, while ducks initiate a fast lower cytokine response followed by the activation of major pattern recognition receptors (TLR7, RIG-I, MDA5) and a persistent cellular response. PMID:23782222

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

    E-print Network

    Gray, Matthew

    . Yin* and W. M. Lai* *College of Veterinary Medicine and Key Laboratory of Animal Disease and Human of amphibians caused by ranaviruses has been reported in the Americas, Europe and Asia (Ariel et al., 2009; Gray

  19. Characterization of a ranavirus isolated from the Chinese giant salamander (Andrias davidianus, Blanchard, 1871) in China

    E-print Network

    Gray, Matthew

    Characterization of a ranavirus isolated from the Chinese giant salamander (Andrias davidianus December 2012 Available online 7 January 2013 Keywords: Characteristics Chinese giant salamander-offs of farmed Chinese giant salamanders (Andrias davidianus) in Leshan, Sichuan Province, China. The farmed

  20. 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

  1. Effects of ranavirus infection of red-eared sliders (Trachemys scripta elegans) on plasma proteins.

    PubMed

    Moore, A Russell; Allender, Matthew C; MacNeill, Amy L

    2014-06-01

    Ranavirus is an emerging disease that infects fish, amphibians, and reptiles. Ranavirus induces an inflammatory response leading to death in many susceptible species. Red-eared sliders (RES; Trachemys scripta elegans) are vulnerable to ranavirus infection and are economically significant chelonians kept in the pet trade and utilized in research. Early identification of RES with inflammatory diseases would allow for isolation of affected individuals and subsequent disease investigation, including molecular testing for ranavirus. Validation of an inexpensive, clinically relevant, and reproducible diagnostic test that detects inflammation in turtles is needed. Although commonly used, plasma protein electrophoresis to detect an inflammatory acute-phase protein response has not been evaluated in a controlled environment in turtles with experimentally induced inflammatory disease. The objective of this study was to measure plasma protein fractions by electrophoresis to determine if an acute-phase protein response occurs in RES during infection with a frog virus 3-like ranavirus (FV3-like virus) isolated from a chelonian. A Bradford assay and agarose gel electrophoresis (AGE) were performed using plasma collected during a study of the effect of temperature on the pathogenesis of ranavirus in RES. In RES at the time of viremia, total albumin (ALB(mg/ml)) and albumin to globulin ratio were significantly lower and beta-globulin percentage was significantly higher in RES exposed to ranavirus (n = 4) as compared to matched, uninfected RES (n = 8). In the last sample collected prior to death, total protein (TP(mg/ml)), ALB(mg/ml), alpha-globulin percentage, and total alpha-globulin (alpha(mg/ml)) were significantly lower in RES exposed to ranavirus (n = 4) than control individuals (n = 8). In summary, FV3-like virus induces a decrease in plasma albumin concentration at the onset ofviremia and decreases in TP(mg/ml, ALB(mg/ml), and alpha(mg/ml) concentrations prior to death in RES as measured by AGE. PMID:25000690

  2. 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

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

    PubMed

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

    2014-01-01

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

  4. 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.

  5. 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

  6. 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

  7. Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239

    PubMed Central

    Wilson, Nancy A.; Reed, Jason; Napoe, Gnankang S.; Piaskowski, Shari; Szymanski, Andy; Furlott, Jessica; Gonzalez, Edna J.; Yant, Levi J.; Maness, Nicholas J.; May, Gemma E.; Soma, Taeko; Reynolds, Matthew R.; Rakasz, Eva; Rudersdorf, Richard; McDermott, Adrian B.; O'Connor, David H.; Friedrich, Thomas C.; Allison, David B.; Patki, Amit; Picker, Louis J.; Burton, Dennis R.; Lin, Jing; Huang, Lingyi; Patel, Deepa; Heindecker, Gwendolyn; Fan, Jiang; Citron, Michael; Horton, Melanie; Wang, Fubao; Liang, Xiaoping; Shiver, John W.; Casimiro, Danilo R.; Watkins, David I.

    2006-01-01

    The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be to reduce the viral set point and preserve memory CD4 lymphocytes. Here we investigated whether vaccine-induced cellular immunity in the absence of any Env-specific antibodies can control viral replication following multiple low-dose challenges with the highly pathogenic SIVmac239 isolate. Eight Mamu-A*01-positive Indian rhesus macaques were vaccinated with simian immunodeficiency virus (SIV) gag, tat, rev, and nef using a DNA prime-adenovirus boost strategy. Peak viremia (P = 0.007) and the chronic phase set point (P = 0.0192) were significantly decreased in the vaccinated cohort, out to 1 year postinfection. Loss of CD4+ memory populations was also ameliorated in vaccinated animals. Interestingly, only one of the eight vaccinees developed Env-specific neutralizing antibodies after infection. The control observed was significantly improved over that observed in animals vaccinated with SIV gag only. Vaccine-induced cellular immune responses can, therefore, exert a measure of control over replication of the AIDS virus in the complete absence of neutralizing antibody and give us hope that a vaccine designed to induce cellular immune responses might control viral replication. PMID:16731926

  8. Prevalence of antibodies to selected viral pathogens in wild boars (Sus scrofa) in Croatia in 2005-06 and 2009-10.

    PubMed

    Roic, Besi; Jemersic, Lorena; Terzic, Svjetlana; Keros, Tomislav; Balatinec, Jelena; Florijancic, Tihomir

    2012-01-01

    We determined prevalence of antibody to selected viral pathogens important for domestic pigs and livestock in 556 wild boar (Sus scrofa) sera collected during 2005-06 and 2009-10 in four counties in Croatia. These counties account for an important part of the Croatian commercial pig production and have a high density of wild boars. Samples were tested for antibodies to porcine parvovirus (PPV), Aujeszky's disease virus (ADV), porcine circovirus type 2 (PCV2), swine influenza virus, porcine respiratory and reproductive syndrome virus (PRRSV), porcine respiratory coronavirus (PRCV), transmissible gastroenteritis virus, and swine vesicular disease virus (SVDV). Antibodies to all of the infectious pathogens except SVDV were detected. There was a statistically significant difference in prevalence between the two periods for PPV, ADV, PCV2, PRRSV, and PRCV, with a higher prevalence of PPV and ADV in the 2009-10 period (P<0.05). During the same period, the prevalence of PCV2, PRRSV, and PRCV was lower (P<0.05). Our results provide information on the current disease exposure and health status of wild boars in Croatia and suggest that wild boars may act as a reservoir for several pathogens and a source of infection for domestic pigs and other livestock as well as humans, especially for ADV. PMID:22247381

  9. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 (CAST) has re...

  11. The Protein Kinase Double-Stranded RNA-Dependent (PKR) Enhances Protection against Disease Cause by a Non-Viral Pathogen

    PubMed Central

    White, Christine L.; Patel, Krupen; Lamb, Bruce; Sen, Ganes C.; Subauste, Carlos S.

    2013-01-01

    PKR is well characterized for its function in antiviral immunity. Using Toxoplasma gondii, we examined if PKR promotes resistance to disease caused by a non-viral pathogen. PKR?/? mice infected with T. gondii exhibited higher parasite load and worsened histopathology in the eye and brain compared to wild-type controls. Susceptibility to toxoplasmosis was not due to defective expression of IFN-?, TNF-?, NOS2 or IL-6 in the retina and brain, differences in IL-10 expression in these organs or to impaired induction of T. gondii-reactive T cells. While macrophages/microglia with defective PKR signaling exhibited unimpaired anti-T. gondii activity in response to IFN-?/TNF-?, these cells were unable to kill the parasite in response to CD40 stimulation. The TRAF6 binding site of CD40, but not the TRAF2,3 binding sites, was required for PKR phosphorylation in response to CD40 ligation in macrophages. TRAF6 co-immunoprecipitated with PKR upon CD40 ligation. TRAF6-PKR interaction appeared to be indirect, since TRAF6 co-immunoprecipitated with TRAF2 and TRAF2 co-immunoprecipitated with PKR, and deficiency of TRAF2 inhibited TRAF6-PKR co-immunoprecipitation as well as PKR phosphorylation induced by CD40 ligation. PKR was required for stimulation of autophagy, accumulation the autophagy molecule LC3 around the parasite, vacuole-lysosomal fusion and killing of T. gondii in CD40-activated macrophages and microglia. Thus, our findings identified PKR as a mediator of anti-microbial activity and promoter of protection against disease caused by a non-viral pathogen, revealed that PKR is activated by CD40 via TRAF6 and TRAF2, and positioned PKR as a link between CD40-TRAF signaling and stimulation of the autophagy pathway. PMID:23990781

  12. 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.

  13. 2011 International Ranavirus Symposium Rachel E. Marschang1, PD DMV, DECZM (Herpetology),

    E-print Network

    Gray, Matthew

    - gens in conservation and ectothermic vertebrate medicine. Although more research is now being carried). An overview of the program, as well as future research directions and slides and videos of most presenta, they are now known to cause die-offs among various classes of ectothermic vertebrates. The role of ranaviruses

  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. One time intranasal vaccination with a modified vaccinia Tiantan strain MVTT(ZCI) protects animals against pathogenic viral challenge.

    PubMed

    Yu, Wenbo; Fang, Qing; Zhu, Weijun; Wang, Haibo; Tien, Po; Zhang, Linqi; Chen, Zhiwei

    2010-02-25

    To combat variola virus in bioterrorist attacks, it is desirable to develop a noninvasive vaccine. Based on the vaccinia Tiantan (VTT) strain, which was historically used to eradicate the smallpox in China, we generated a modified VTT (MVTT(ZCI)) by removing the hemagglutinin gene and an 11,944bp genomic region from HindIII fragment C2L to F3L. MVTT(ZCI) was characterized for its host cell range in vitro and preclinical safety and efficacy profiles in mice. Despite replication-competency in some cell lines, unlike VTT, MVTT(ZCI) did not cause death after intracranial injection or body weight loss after intranasal inoculation. MVTT(ZCI) did not replicate in mouse brain and was safe in immunodeficient mice. MVTT(ZCI) induced neutralizing antibodies via the intranasal route of immunization. One time intranasal immunization protected animals from the challenge of the pathogenic vaccinia WR strain. This study established proof-of-concept that the attenuated replicating MVTT(ZCI) may serve as a safe noninvasive smallpox vaccine candidate. PMID:20045097

  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. A member of the cathelicidin family of antimicrobial peptides is produced in the upper airway of the chinchilla and its mRNA expression is altered by common viral and bacterial co-pathogens of otitis media

    Microsoft Academic Search

    Glen McGillivary; William C. Ray; Charles L. Bevins; Robert S. Munson Jr.; Lauren O. Bakaletz

    2007-01-01

    Cationic antimicrobial peptides (AMPs), a component of the innate immune system, play a major role in defense of mucosal surfaces against a wide spectrum of microorganisms such as viral and bacterial co-pathogens of the polymicrobial disease otitis media (OM). To further understand the role of AMPs in OM, we cloned a cDNA encoding a cathelicidin homolog (cCRAMP) from upper respiratory

  18. Viral apoptotic mimicry.

    PubMed

    Amara, Ali; Mercer, Jason

    2015-08-01

    As opportunistic pathogens, viruses have evolved many elegant strategies to manipulate host cells for infectious entry and replication. Viral apoptotic mimicry, defined by the exposure of phosphatidylserine - a marker for apoptosis - on the pathogen surface, is emerging as a common theme used by enveloped viruses to promote infection. Focusing on the four best described examples (vaccinia virus, dengue virus, Ebola virus and pseudotyped lentivirus), we summarize our current understanding of apoptotic mimicry as a mechanism for virus entry, binding and immune evasion. We also describe recent examples of non-enveloped viruses that use this mimicry strategy, and discuss future directions and how viral apoptotic mimicry could be targeted therapeutically. PMID:26052667

  19. 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

  20. SEROLOGIC SURVEY FOR SELECTED VIRAL PATHOGENS IN FREE RANGING ENDANGERED EUROPEAN MINK (MUSTELA LUTREOLA) AND OTHER MUSTELIDS FROM SOUTH-WESTERN FRANCE

    Microsoft Academic Search

    Joost Philippa; Christine Fournier-Chambrillon; Pascal Fournier; Willem Schaftenaar; Marco van de Bildt; Rob van Herweijnen; Thijs Kuiken; Marie Liabeuf; Sebastien Ditcharry; Laurent Joubert

    2008-01-01

    To investigate the possible role of selected pathogens in the decline of endangered European mink (Mustela lutreola) populations and the potential for these pathogens to affect mink survival, a serologic survey was conducted using serum samples collected from March 1996 to March 2003 in eight departments of south-western France. In total, 481 free-ranging individuals of five mustelid species (including the

  1. 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.

  2. First case of ranavirus and associated morbidity and mortality in an eastern mud turtle Kinosternon subrubrum in South Carolina.

    PubMed

    Winzeler, Megan E; Hamilton, Matthew T; Tuberville, Tracey D; Lance, Stacey L

    2015-05-11

    Ranaviruses are double-stranded DNA viruses that infect amphibians, fish, and reptiles, causing global epidemics in some amphibian populations. It is important to identify new species that may be susceptible to the disease, particularly if they reside in the same habitat as other at-risk species. On the Savannah River Site (SRS) in Aiken, South Carolina, USA, ranaviruses are present in several amphibian populations, but information is lacking on the presence, prevalence, and morbidity of the virus in reptile species. An eastern mud turtle Kinosternon subrubrum captured on the SRS in April 2014 exhibited clinical signs of a ranaviral infection, including oral plaque and conjunctivitis. Quantitative PCR analyses of DNA from liver tissue, ocular, oral, nasal, and cloacal swabs were all positive for ranavirus, and sequencing of the template confirmed infection with a FV3-like ranavirus. Histopathologic examination of postmortem tissue samples revealed ulceration of the oral and tracheal mucosa, intracytoplasmic epithelial inclusions in the oral mucosa and tongue sections, individualized and clusters of melanomacrophages in the liver, and bacterial rods located in the liver, kidney, heart, stomach, and small intestine. This is the first report of morbidity and mortality of a mud turtle with a systemic ranaviral infection. PMID:25958808

  3. 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

  4. 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

  5. Pharyngitis - viral

    MedlinePLUS

    ... pharyngitis. Pharyngitis may occur as part of a viral infection that also involves other organs, such as the ... when a sore throat is due to a viral infection. The antibiotics will not help. Using them to ...

  6. 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;

  7. 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

  8. Common childhood viral infections.

    PubMed

    Alter, Sherman J; Bennett, Jeffrey S; Koranyi, Katylin; Kreppel, Andrew; Simon, Ryan

    2015-02-01

    Infections caused by viruses are universal during childhood and adolescence. Clinicians will regularly care for children and adolescents who present with infections caused by a wide number of viral pathogens. These infections have varied presentations. Many infections may have clinical presentations that are specific to the infecting virus but present differently, based on the age and immunocompetence of the patient. Some children are directly impacted early in their lives when maternal disease results in an in utero infection (cytomegalovirus, rubella virus, or parvovirus B19). Other viruses may infect children in a predictable pattern as they grow older (rhinovirus or influenza virus). Fortunately, many viral infections frequently encountered in the past are no longer extant due to widespread immunization efforts. Recognition of these vaccine-preventable infections is important because outbreaks of some of these diseases (mumps or measles) continue to occur in the United States. Vigilance in vaccine programs against these viral agents can prevent their re-emergence. In addition, an increasing number of viral infections (herpes simplex virus, influenza virus, varicella zoster virus, or cytomegalovirus) can now be successfully treated with antiviral medications. Most viral infections in children result in self-limited illness and are treated symptomatically and infected children experience full recovery. This review will address the epidemiology, clinical presentation, diagnosis, treatment, and prevention of viral infections commonly encountered by the clinician. PMID:25703483

  9. Infection studies with two highly pathogenic avian influenza strains (Vietnamese and Indonesian) in Pekin ducks (Anas platyrhynchos), with particular reference to clinical disease, tissue tropism and viral shedding

    Microsoft Academic Search

    John Bingham; Diane J. Green; Sue Lowther; Jessica Klippel; Simon Burggraaf; Danielle E. Anderson; Hendra Wibawa; Dong Manh Hoa; Ngo Thanh Long; Pham Phong Vu; Deborah J. Middleton; Peter W. Daniels

    2009-01-01

    Pekin ducks were infected by the mucosal route (oral, nasal, ocular) with one of two strains of Eurasian lineage H5N1 highly pathogenic avian influenza virus: A\\/Muscovy duck\\/Vietnam\\/453\\/2004 and A\\/duck\\/Indramayu\\/BBVW\\/109\\/2006 (from Indonesia). Ducks were killed humanely on days 1, 2, 3, 5 and 7 after challenge, or whenever morbidity was severe enough to justify euthanasia. Morbidity was recorded by observation of

  10. 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

  11. Serologic survey for selected viral pathogens in free-ranging endangered European mink (Mustela lutreola) and other mustelids from south-western France.

    PubMed

    Philippa, Joost; Fournier-Chambrillon, Christine; Fournier, Pascal; Schaftenaar, Willem; van de Bildt, Marco; van Herweijnen, Rob; Kuiken, Thijs; Liabeuf, Marie; Ditcharry, Sébastien; Joubert, Laurent; Bégnier, Michel; Osterhaus, Ab

    2008-10-01

    To investigate the possible role of selected pathogens in the decline of endangered European mink (Mustela lutreola) populations and the potential for these pathogens to affect mink survival, a serologic survey was conducted using serum samples collected from March 1996 to March 2003 in eight departments of south-western France. In total, 481 free-ranging individuals of five mustelid species (including the European mink) were tested. Sympatric mustelids can serve as sentinels to determine the presence of antibodies to viruses in the study area that could potentially infect mink. Antibodies to Canine distemper virus (CDV) were detected in all species; 9% of 127 European mink, 20% of 210 polecats (Mustela putorius), 5% of 112 American mink (Mustela vison), 33% of 21 stone marten (Martes foina) and 5% of 20 pine marten (Martes martes). Antibody prevalence was significantly higher in stone marten and polecats, possibly because their ranges overlap more closely with that of domestic species than that of the other species tested. Antibodies to Canine adenovirus were detected in all species but the pine marten; antibody prevalence estimates ranging from 2% to 10%. Antibodies to canine parainfluenza virus were detected in 1% of European mink, 1% of American mink and 5% of tested polecats but were not detected in Martes species. Antibodies to Rabies virus (RV) were detected in three animals, possibly because of interspecies transmission of bat lyssaviruses as the sampling area is considered to be free of RV, or to a lack of test specificity, as antibody titers were low. The high antibody prevalence to potentially lethal CDV suggests that this pathogen could have significant effects on the free-ranging populations and has implications for the conservation efforts for the endangered European mink. PMID:18957635

  12. A novel cytotoxic sequence contributes to influenza A viral protein PB1-F2 pathogenicity and predisposition to secondary bacterial infection.

    PubMed

    Alymova, Irina V; 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

  13. 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

  14. The pathogenicity determinant of Citrus tristeza virus causing the seedling yellows syndrome maps at the 3'-terminal region of the viral genome.

    PubMed

    Albiach-Marti, Maria R; Robertson, Cecile; Gowda, Siddarame; Tatineni, Satyanarayana; Belliure, Belén; Garnsey, Stephen M; Folimonova, Svetlana Y; Moreno, Pedro; Dawson, William O

    2010-01-01

    Citrus tristeza virus (CTV) (genus Closterovirus, family Closteroviridae) causes some of the more important viral diseases of citrus worldwide. The ability to map disease-inducing determinants of CTV is needed to develop better diagnostic and disease control procedures. A distinctive phenotype of some isolates of CTV is the ability to induce seedling yellows (SY) in sour orange, lemon and grapefruit seedlings. In Florida, the decline isolate of CTV, T36, induces SY, whereas a widely distributed mild isolate, T30, does not. To delimit the viral sequences associated with the SY syndrome, we created a number of T36/T30 hybrids by substituting T30 sequences into different regions of the 3' half of the genome of an infectious cDNA of T36. Eleven T36/T30 hybrids replicated in Nicotiana benthamiana protoplasts. Five of these hybrids formed viable virions that were mechanically transmitted to Citrus macrophylla, a permissive host for CTV. All induced systemic infections, similar to that of the parental T36 clone. Tissues from these C. macrophylla source plants were then used to graft inoculate sour orange and grapefruit seedlings. Inoculation with three of the T30/T36 hybrid constructs induced SY symptoms identical to those of T36; however, two hybrids with T30 substitutions in the p23-3' nontranslated region (NTR) (nucleotides 18 394-19 296) failed to induce SY. Sour orange seedlings infected with a recombinant non-SY p23-3' NTR hybrid also remained symptomless when challenged with the parental virus (T36), demonstrating the potential feasibility of using engineered constructs of CTV to mitigate disease. PMID:20078776

  15. Viral meningitis and encephalitis: traditional and emerging viral agents.

    PubMed

    Romero, José R; Newland, Jason G

    2003-04-01

    In the United States, the annual number of central nervous system (CNS) infections that occur as a result of viral agents far exceeds that of infections caused by bacteria, yeast, molds, and protozoa combined. The recent incursion of West Nile virus (WNV) into North America has led to a dramatic change in the incidence and epidemiology of summer-associated viral CNS disease. As a result of increased testing for WNV, lesser known viral causes of CNS infection have been identified. Even the epidemiology of such traditional viral neuropathogens as rabies has changed in recent years. This review provides an overview of viruses traditionally associated with meningitis and encephalitis (enteroviruses, La Crosse virus, St. Louis encephalitis virus, eastern and western equine viruses, varicella-zoster virus), as well as several of the less common (Powassan virus, lymphocytic choriomeningitis virus, Colorado tick fever virus, rabies virus, influenza viruses, etc.) and emerging (West Nile virus) viral pathogens. PMID:12881794

  16. Identification of a novel NPR1-like gene from Nicotiana glutinosa and its role in resistance to fungal, bacterial and viral pathogens.

    PubMed

    Zhang, Y; Shi, J; Liu, J-Y; Zhang, Y; Zhang, J-D; Guo, X-Q

    2010-01-01

    The NPR1 or NPR1-like genes play a pivotal role in systemic acquired resistance in plants. Here, we isolated and identified a novel tobacco (Nicotiana glutinosa) NPR1-like gene (designated as NgNPR3). The full-length cDNA is 2049 bp in length with a 1767 bp open reading frame which encodes a 588 amino acids protein with an estimated molecular mass of 66 kDa and a calculated pI of 7.14. Homology analysis suggested that the NgNPR3 protein shares significant similarity to AtNPR3 of Arabidopsis. Transient expression assay of NgNPR3-GFP fusion gene in onion epidermal cells revealed that the NgNPR3 protein was localized to the cytoplasm and moved into the nucleus after redox change. RT-PCR results indicated that NgNPR3 was up-regulated after treatment with SA, INA, H(2)O(2,) and MeJA, which play important roles in various resistance responses in tobacco. Transcriptional level of NgNPR3 was also up-regulated after inoculation with Rhizoctonia solani, Phytophthora parasitica, Alternaria alternata, Pseudomonas solanacearum, and potato virus Y (PVY), respectively. When NgNPR3 was overexpressed in N. tabacum cv. Samsun plants, the transgenic plants showed enhanced resistance to the pathogens A. alternate, P. solanacearum and PVY. Furthermore, NgNPR3-mediated disease resistance is dosage-dependent. Our results suggest that NgNPR3 could be a putative NPR1-like gene, and might play an important role in resistance to a broad range of pathogens in tobacco. PMID:20653885

  17. 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

  18. IFITM Proteins Restrict Viral Membrane Hemifusion

    E-print Network

    2013-01-01

    an intermediate of fusion, referred to as a cold arrestedcold arrested state (CAS), PLOS Pathogens | www.plospathogens.org January 2013 | Volume 9 | Issue 1 | e1003124 Restriction of Viral Membrane Fusion

  19. Viral Infection in Renal Transplant Recipients

    PubMed Central

    Cukuranovic, Jovana; Ugrenovic, Sladjana; Jovanovic, Ivan; Visnjic, Milan; Stefanovic, Vladisav

    2012-01-01

    Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens. PMID:22654630

  20. 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

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

    PubMed Central

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

    2013-01-01

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

  2. 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...

  3. 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.

  4. 6 Immunopathogenesis of viral hepatitis

    Microsoft Academic Search

    Barbara Rehermann

    1996-01-01

    More than 500 million people world-wide suffer from viral hepatitis which can be caused by a variety of distinct infectious agents. The spectrum of disease, which ranges from acute self-limited hepatitis to liver cirrhosis, not only reflects the different biological properties and pathogenicity of the hepatitis viruses, but is also the result of the specific interaction between each virus and

  5. 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

  6. Present and Future Projections of Habitat Suitability of the Asian Tiger Mosquito, a Vector of Viral Pathogens, from Global Climate Simulations.

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

    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 (GCM) 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 21st 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 about 2.4 billion individuals in a land area of nearly 20 million square kilometres 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.

  7. 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

  8. Viral encephalitis in travellers.

    PubMed

    Aryee, Anna; Thwaites, Guy

    2015-02-01

    Viral infections are the commonest cause of encephalitis, and the purpose of this article is to inform UK clinicians of the presentation, diagnosis and management of viral encephalitis in travellers returning to the UK. The classical presentation is as a triad of fever, headache and altered mental state. There may be other findings either on examination or on imaging which, together with a travel history, may give clues as to the aetiology. It is important to note that in high- and middle-income countries the commonest cause of viral encephalitis is herpes simplex. This, coupled with the fact that untreated herpes simplex encephalitis (HSE) has a mortality of over 70%, means that aciclovir should always be included in the treatment of patients with suspected encephalitis, regardless of their history of travel. In the UK, the Rare and Imported Pathogens Laboratory (RIPL) at Public Health England can perform specific polymerase chain reaction (PCR) analyses on blood and CSF samples for many imported causes of viral encephalitis. PMID:25650207

  9. A viral deubiquitylating enzyme targets viral RNA-dependent RNA polymerase and affects viral infectivity

    PubMed Central

    Chenon, Mélanie; Camborde, Laurent; Cheminant, Soizic; Jupin, Isabelle

    2012-01-01

    Selective protein degradation via the ubiquitin-proteasome system (UPS) plays an essential role in many major cellular processes, including host–pathogen interactions. We previously reported that the tightly regulated viral RNA-dependent RNA polymerase (RdRp) of the positive-strand RNA virus Turnip yellow mosaic virus (TYMV) is degraded by the UPS in infected cells, a process that affects viral infectivity. Here, we show that the TYMV 98K replication protein can counteract this degradation process thanks to its proteinase domain. In-vitro assays revealed that the recombinant proteinase domain is a functional ovarian tumour (OTU)-like deubiquitylating enzyme (DUB), as is the 98K produced during viral infection. We also demonstrate that 98K mediates in-vivo deubiquitylation of TYMV RdRp protein—its binding partner within replication complexes—leading to its stabilization. Finally, we show that this DUB activity contributes to viral infectivity in plant cells. The identification of viral RdRp as a specific substrate of the viral DUB enzyme thus reveals the intricate interplay between ubiquitylation, deubiquitylation and the interaction between viral proteins in controlling levels of RdRp and viral infectivity. PMID:22117220

  10. Complete genome sequence of a common midwife toad virus-like ranavirus associated with mass mortalities in wild amphibians in the Netherlands.

    PubMed

    van Beurden, Steven J; Hughes, Joseph; Saucedo, Bernardo; Rijks, Jolianne; Kik, Marja; Haenen, Olga L M; Engelsma, Marc Y; Gröne, Andrea; Verheije, M Helene; Wilkie, Gavin

    2014-01-01

    A ranavirus associated with mass mortalities in wild water frogs (Pelophylax spp.) and other amphibians in the Netherlands since 2010 was isolated, and its complete genome sequence was determined. The virus has a genome of 107,772 bp and shows 96.5% sequence identity with the common midwife toad virus from Spain. PMID:25540340

  11. Long-term study of an infection with ranaviruses in a group of edible frogs (Pelophylax kl. esculentus) and partial characterization of

    E-print Network

    Gray, Matthew

    of a ranavirus from Lithobates pipiens (formerly Rana pipiens) in 1965 (Granoff et al., 1965), an increasing was detected repeatedly, but a new rana- virus was isolated in association with the second mass-mortality event to the Rana esculenta virus (REV-like) clade in the phylogenetic analysis. Furthermore, a quiescent infection

  12. Pathogen biology Meeting report

    E-print Network

    Gray, Matthew

    community had not convened specifically to discuss the current state of knowledge on rana- viruses. Thus, 23. In 1965, the first ranaviruses were isolated from northern leopard frogs (Lithobates pipiens) by Allan identified as rana- viruses, were associated with mortality events in ecologically and economically important

  13. 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...

  14. 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

  15. Effect of ultraviolet germicidal irradiation on viral aerosols.

    PubMed

    Walker, Christopher M; Ko, Gwangpyo

    2007-08-01

    Ultraviolet (UV) germicidal air disinfection is an engineering method used to control the airborne transmission of pathogenic microorganisms in high-risk settings. Despite the recent emergence of respiratory viral pathogens such as SARS and avian influenza viruses, UV disinfection of pathogenic viral aerosols has not been examined. Hence, we characterized the UV disinfection of viral aerosols using the bacteriophage MS2, adenovirus, and coronavirus. Our objectives were to characterize the effect of nebulization and air sampling on the survival of important viral pathogens, quantitatively characterize and estimate the UV susceptibility of pathogenic viral aerosols, and evaluate the effect of relative humidity (RH) on the susceptibility of viral aerosols, to 254 nm UV-C. The viruses were aerosolized into an experimental chamber using a six-jet Collison nebulizer, exposed to 254 nm UV, and sampled using an AGI-30 liquid impinger. Both the MS2 and adenovirus aerosols were very resistant to UV air disinfection, with a reduction of less than 1 logarithm in viable viral aerosols at a UV dose of 2608 microW s/cm2. The susceptibility of coronavirus aerosols was 7-10 times that of the MS2 and adenovirus aerosols. Unlike bacterial aerosols, there was no significant protective effect of high RH on UV susceptibility of the tested viral aerosols. We confirmed that the UV disinfection rate differs greatly between viral aerosols and viruses suspended in liquid. PMID:17822117

  16. 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

  17. DC-SIGN: escape mechanism for pathogens

    Microsoft Academic Search

    Teunis B. H. Geijtenbeek; Yvette van Kooyk

    2003-01-01

    Dendritic cells (DCs) are crucial in the defence against pathogens. Invading pathogens are recognized by Toll-like receptors (TLRs) and receptors such as C-type lectins expressed on the surface of DCs. However, it is becoming evident that some pathogens, including viruses, such as HIV-1, and non-viral pathogens, such as Mycobacterium tuberculosis, subvert DC functions to escape immune surveillance by targeting the

  18. 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

  19. Endosomal vesicles as vehicles for viral genomes.

    PubMed

    Nour, Adel M; Modis, Yorgo

    2014-08-01

    The endocytic pathway is the principal cell entry pathway for large cargos and pathogens. Among the wide variety of specialized lipid structures within endosomes, the intraluminal vesicles (ILVs) formed in early endosomes (EEs) and transferred to late endosomal compartments are emerging as critical effectors of viral infection and immune recognition. Various viruses deliver their genomes into these ILVs, which serve as vehicles to transport the genome to the nuclear periphery for replication. When secreted as exosomes, ILVs containing viral genomes can infect permissive cells or activate immune responses in myeloid cells. We therefore propose that endosomal ILVs and exosomes are key effectors of viral pathogenesis. PMID:24746011

  20. MARINE MAMMAL DISEASES: PATHOGENS AND PROCESSES

    EPA Science Inventory

    The purpose of this chapter is to provide a concise overview of the pathogens and processes that alter the health of marine mammals. Viral disease is the most common etiology of significant mortality events in marine mammals. Discussion of viral disease focuses on effects in the ...

  1. 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.

  2. Preferential Amplification of Pathogenic Sequences.

    PubMed

    Ge, Fang; Parker, Jayme; Chul Choi, Sang; Layer, Mark; Ross, Katherine; Jilly, Bernard; Chen, Jack

    2015-01-01

    The application of next generation sequencing (NGS) technology in the diagnosis of human pathogens is hindered by the fact that pathogenic sequences, especially viral, are often scarce in human clinical specimens. This known disproportion leads to the requirement of subsequent deep sequencing and extensive bioinformatics analysis. Here we report a method we called "Preferential Amplification of Pathogenic Sequences (PATHseq)" that can be used to greatly enrich pathogenic sequences. Using a computer program, we developed 8-, 9-, and 10-mer oligonucleotides called "non-human primers" that do not match the most abundant human transcripts, but instead selectively match transcripts of human pathogens. Instead of using random primers in the construction of cDNA libraries, the PATHseq method recruits these short non-human primers, which in turn, preferentially amplifies non-human, presumably pathogenic sequences. Using this method, we were able to enrich pathogenic sequences up to 200-fold in the final sequencing library. This method does not require prior knowledge of the pathogen or assumption of the infection; therefore, it provides a fast and sequence-independent approach for detection and identification of human viruses and other pathogens. The PATHseq method, coupled with NGS technology, can be broadly used in identification of known human pathogens and discovery of new pathogens. PMID:26067233

  3. Preferential Amplification of Pathogenic Sequences

    PubMed Central

    Ge, Fang; Parker, Jayme; Chul Choi, Sang; Layer, Mark; Ross, Katherine; Jilly, Bernard; Chen, Jack

    2015-01-01

    The application of next generation sequencing (NGS) technology in the diagnosis of human pathogens is hindered by the fact that pathogenic sequences, especially viral, are often scarce in human clinical specimens. This known disproportion leads to the requirement of subsequent deep sequencing and extensive bioinformatics analysis. Here we report a method we called “Preferential Amplification of Pathogenic Sequences (PATHseq)” that can be used to greatly enrich pathogenic sequences. Using a computer program, we developed 8-, 9-, and 10-mer oligonucleotides called “non-human primers” that do not match the most abundant human transcripts, but instead selectively match transcripts of human pathogens. Instead of using random primers in the construction of cDNA libraries, the PATHseq method recruits these short non-human primers, which in turn, preferentially amplifies non-human, presumably pathogenic sequences. Using this method, we were able to enrich pathogenic sequences up to 200-fold in the final sequencing library. This method does not require prior knowledge of the pathogen or assumption of the infection; therefore, it provides a fast and sequence-independent approach for detection and identification of human viruses and other pathogens. The PATHseq method, coupled with NGS technology, can be broadly used in identification of known human pathogens and discovery of new pathogens. PMID:26067233

  4. Review article Emerging viral diseases of fish and shrimp

    E-print Network

    Paris-Sud XI, Université de

    Review article Emerging viral diseases of fish and shrimp Peter J. WALKER 1*, James R. WINTON 2 1 and characteristics of aquaculture, the major viral pathogens of fish and shrimp and their impacts, and the particular the challenges presented by climate change. disease emergence / shrimp / fish / virus Table of contents 1

  5. 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

  6. Viral subversion of nucleocytoplasmic trafficking.

    PubMed

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

    2014-02-01

    Trafficking of proteins and RNA into and out of the nucleus occurs through the nuclear pore complex (NPC). Because of 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, whereas 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. As 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. 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

  7. PAK in pathogen-host interactions.

    PubMed

    Semblat, Jean-Philippe; Doerig, Christian

    2012-04-01

    Eukaryotic, prokaryotic and viral pathogens are known to interfere with signaling pathways of their host to promote their own survival and proliferation. Here, we present selected examples of modulation of PAK activity in human cells by both intracellular and extracellular pathogens, focusing on one eukaryotic pathogen, the human malaria parasite Plasmodium falciparum, two Gram-negative bacteria (Helicobacter pylori and Pseudomonas aeruginosa), and two viruses belonging to distinct groups, the lentivirus HIV and the orthomyxovirus Influenza virus A. PMID:23125952

  8. Modulation of PKR activity in cells infected by bovine viral diarrhea virus

    Microsoft Academic Search

    Laura H. V. G. Gil; Alberto L. van Olphen; Suresh K. Mittal; Ruben O. Donis

    2006-01-01

    Bovine viral diarrhea virus is an important animal pathogen. The cytopathic and noncytopathic biotypes of the virus are associated with distinct pathologic entities. A striking difference between the two biotypes is viral RNA accumulation in infected cells. Viral dsRNA is thought to activate protein kinase PKR; an important mediator of innate immunity. In this study, we investigated PKR activation and

  9. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. Mutations in the Highly Conserved SLQYLA Motif of Vif in a Simian-Human Immunodeficiency Virus Result in a Less Pathogenic Virus and is Associated with G-to-A Mutations in the Viral Genome

    PubMed Central

    Schmitt, Kimberly; Hill, M. Sarah; Ruiz, Autumn; Culley, Nathan; Pinson, David M.; Wong, Scott W.

    2014-01-01

    The simian-human immunodeficiency virus (SHIV)/macaque model for human immunodeficiency virus type 1 has become a useful tool to assess the role of accessory genes in lentiviral pathogenesis. In this study, we introduced two amino acid changes in the highly conserved SLQYLA domain (to AAQYLA) of the SIV Vif protein. The resulting virus, SHIVVifAAQYLA, was used to infect three macaques, which were followed for over six months. Plasma viral loads and circulating CD4+ T cell levels were assessed during the course of infection. The three macaques inoculated with SHIVVifAAQYLA did not develop significant CD4+ T cell loss over the course of their infection, had plasma viral RNA loads that were over 100-fold lower than macaques inoculated with parental SHIVKU-1bMC33, and developed no histological lesions in lymphoid tissues. DNA and RT-PCR analysis revealed that only a select number of tissues were infected with this virus. Sequence analysis indicates that the site-directed changes were stable during the first three weeks after inoculation but thereafter the S147A amino acid substitution changed to a threonine in two of three macaques. The L148A substitution remained stable in the vif amplified from the PBMC of all three macaques. Sequence analysis of vif, vpu, env and nef genes revealed G-to-A mutations in the genes amplified from macaques inoculated with SHIVVifAAQYLA, which were higher than in a macaque inoculated with parental SHIVKU-1bMC33. We found that the majority (>85%) of the G-to-A mutations were in the context of 5?-TC (minus strand) and not 5?-CC, suggestive that one or more of the rhesus APOBEC3 proteins may be responsible for the observed mutational patterns with rhesus APOBEC3G for a minority of the mutations since its GG-to-AG mutational pattern was infrequently detected. Finally, macaques inoculated with SHIVVifAAQYLA developed immunoprecipitating antibody responses against the virus. The results from this study provide the first in vivo evidence of the importance of the SLQYLA domain in viral pathogenesis and show that targeted mutations in vif can lead to a persistent infection with G-to-A changes accumulating in the viral genome. PMID:19027134

  12. 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...

  13. 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...

  14. 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...

  15. Dendritic cells in viral infections.

    PubMed

    Belz, Gabrielle; Mount, Adele; Masson, Frederick

    2009-01-01

    Antigen presenting cells (APCs) are recognized as key initiators of adaptive immunity, particularly to pathogens, by eliciting a rapid and potent immune attack on infected cells. Amongst APCs, dendritic cells (DCs) are specially equipped to initiate and regulate immune responses in a manner that depends on signals they receive from microbes and their cellular environment. To achieve this, they are equipped with highly efficient mechanisms that allow them to detect pathogens, to capture, process and present antigens, and to activate and guide the differentiation of T cells into effector and memory cells. DCs can no longer be considered as a homogeneous cell type performing a single function, but are heterogeneous both in phenotype, function and dependence on inflammatory stimuli for their formation and responsiveness. Recent studies of DC subtypes have highlighted the contrasting roles of different professional APCs in activating divergent arms of the immune response towards pathogens. In this review, we discuss the progress that has been made in dissecting the attributes of different DC subsets that migrate into, or reside permanently, within lymphoid tissues and their putative roles in the induction of the anti-viral immune response. PMID:19031021

  16. A proteomics perspective on viral DNA sensors in host defense and viral immune evasion mechanisms.

    PubMed

    Crow, Marni S; Javitt, Aaron; Cristea, Ileana M

    2015-06-01

    The sensing of viral DNA is an essential step of cellular immune response to infections with DNA viruses. These human pathogens are spread worldwide, triggering a wide range of virus-induced diseases, and are associated with high levels of morbidity and mortality. Despite similarities between DNA molecules, mammalian cells have the remarkable ability to distinguish viral DNA from their own DNA. This detection is carried out by specialized antiviral proteins, called DNA sensors. These sensors bind to foreign DNA to activate downstream immune signaling pathways and alert neighboring cells by eliciting the expression of antiviral cytokines. The sensing of viral DNA was shown to occur both in the cytoplasm and in the nucleus of infected cells, disproving the notion that sensing occurred by simple spatial separation of viral and host DNA. A number of omic approaches, in particular, mass-spectrometry-based proteomic methods, have significantly contributed to the constantly evolving field of viral DNA sensing. Here, we review the impact of omic methods on the identification of viral DNA sensors, as well as on the characterization of mechanisms involved in host defense or viral immune evasion. PMID:25728651

  17. Pathogenicity of frog virus 3-like virus in red-eared slider turtles (Trachemys scripta elegans) at two environmental temperatures.

    PubMed

    Allender, M C; Mitchell, M A; Torres, T; Sekowska, J; Driskell, E A

    2013-01-01

    Ranaviral disease has affected several species of reptiles, but disease progression and mortality in relation to environmental temperature has yet to be determined. In this study, two separate trials challenged adult female red-eared slider turtles (Trachemys scripta elegans) with a ranavirus (frog virus 3-like virus; FV3) isolate at environmental temperatures of 22 °C (n = 4) and 28 °C (n = 4). The mortality rates in the turtles in the 22 °C and 28 °C trials were 100% and 50%, respectively. Median survival time for turtles exposed to FV3 at 22 °C was 24 days, while it was 30 days in the group kept at 28 °C. Consistent microscopical lesions were observed only in the group inoculated at 22 °C and included fibrinoid necrosis of vessels in the spleen, vascular and sinusoidal thrombi in the liver, necrotizing myositis and a mild heterophilic interstitial pneumonia. Quantitative polymerase chain reaction, targeting a conserved portion of the major capsid protein, was able to detect virus copies in whole blood, oral and cloacal swabs, tongue, skeletal muscle, lung, heart, liver, spleen, ovary and kidney. Viral copy number in ante-mortem clinical samples was non-significantly highest in whole blood, while kidney had the highest viral copy number in post-mortem samples. All samples had higher virus copy number in turtles exposed to FV3 at 22 °C compared with 28 °C. This study determined that environmental temperature affects the survival and disease progression in ranavirus-infected red-eared slider turtles, which will aid in managing animals in a clinical or free-ranging setting. PMID:23582975

  18. Neuroepidemiology and the epidemiology of viral infections of the nervous system.

    PubMed

    Sejvar, James

    2014-01-01

    The field of neurovirology will undoubtedly experience evolution and change in the years to come. The epidemiology of viral CNS diseases continues to change, and as our understanding of the pathogenesis and pathophysiology associated with viral agents grows, so does our understanding of the behavior of these pathogens among populations. The appearance of viral pathogens in newsettings, new or unrecognized modes of transmission,and the emergence of previously unrecognized pathogens will continue to challenge our laboratory diagnostic and epidemiologic capabilities. However, each lesson that is learned from this evolving epidemiology will hopefully result in improved surveillance, diagnostic,and treatment and prevention capabilities. PMID:25015481

  19. 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

  20. 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

  1. Pathogenic Simian Immunodeficiency Virus Infection Is Associated

    E-print Network

    Wang, David

    -level tax- onomy of enteric bacteria was detected. Thus, enteric viral infections may contribute to AIDS enPathogenic Simian Immunodeficiency Virus Infection Is Associated with Expansion of the Enteric candidate etiologies for AIDS enteropathy, we used next-generation sequencing to define the enteric virome

  2. Prevalence of selected pathogens in western pond turtles and sympatric introduced red-eared sliders in California, USA.

    PubMed

    Silbernagel, C; Clifford, D L; Bettaso, J; Worth, S; Foley, J

    2013-11-25

    Pathogen introduction by invasive species has been speculated to be a cause of declining western pond turtle Emys marmorata populations in California, USA. This study determined the prevalence of Ranavirus spp., Herpesvirus spp., Mycoplasma spp. (via polymerase chain reaction of blood and nasal flush contents), and Salmonella spp. infection (via fecal culture) in native E. marmorata and invasive red-eared sliders Trachemys scripta elegans and compared infection prevalence in E. marmorata populations sympatric with T. scripta elegans to E. marmorata populations that were not sympatric by sampling 145 E. marmorata and 33 T. scripta elegans at 10 study sites throughout California. Mycoplasma spp. were detected in both species: prevalence in E. marmorata was 7.8% in the northern, 9.8% in the central, and 23.3% in the southern California regions. In T. scripta elegans, Mycoplasma spp. were not detected in the northern California region but were detected at 4.5 and 14.3% in the central and southern regions, respectively. All turtles tested negative for Herpesvirus spp. and Ranavirus spp. Enteric bacteria but not Salmonella spp. were isolated from feces. E. marmorata populations that were sympatric with T. scripta elegans did not have increased risk of Mycoplasma spp. infection. For E. marmorata, there was a significant association between Mycoplasma spp. infection and lower body weight and being located in the southern California region. This study is the first of its kind to document pathogen prevalence in native E. marmorata habitats and those sympatric with T. scripta elegans in California. PMID:24270022

  3. 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.

  4. Pathogen intelligence

    PubMed Central

    Steinert, Michael

    2014-01-01

    Different species inhabit different sensory worlds and thus have evolved diverse means of processing information, learning and memory. In the escalated arms race with host defense, each pathogenic bacterium not only has evolved its individual cellular sensing and behavior, but also collective sensing, interbacterial communication, distributed information processing, joint decision making, dissociative behavior, and the phenotypic and genotypic heterogeneity necessary for epidemiologic success. Moreover, pathogenic populations take advantage of dormancy strategies and rapid evolutionary speed, which allow them to save co-generated intelligent traits in a collective genomic memory. This review discusses how these mechanisms add further levels of complexity to bacterial pathogenicity and transmission, and how mining for these mechanisms could help to develop new anti-infective strategies. PMID:24551600

  5. Pathogen intelligence.

    PubMed

    Steinert, Michael

    2014-01-01

    Different species inhabit different sensory worlds and thus have evolved diverse means of processing information, learning and memory. In the escalated arms race with host defense, each pathogenic bacterium not only has evolved its individual cellular sensing and behavior, but also collective sensing, interbacterial communication, distributed information processing, joint decision making, dissociative behavior, and the phenotypic and genotypic heterogeneity necessary for epidemiologic success. Moreover, pathogenic populations take advantage of dormancy strategies and rapid evolutionary speed, which allow them to save co-generated intelligent traits in a collective genomic memory. This review discusses how these mechanisms add further levels of complexity to bacterial pathogenicity and transmission, and how mining for these mechanisms could help to develop new anti-infective strategies. PMID:24551600

  6. Controls on pathogen species richness in plants introduced and native ranges: roles of residence time, range size and host traits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction of hosts to new geographic regions allows them to escape many pathogens, raising two questions. How quickly do introduced hosts accumulate pathogens? Do the same factors control pathogen accumulation as in the native range? We analyzed fungal and viral pathogen species richness on 124 p...

  7. GENE EXPRESSION CHANGES IN MDBK CELLS INFECTED WITH GENOTYPE 2 BOVINE VIRAL DIARRHOEA VIRUS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea viruses (BVDV) are ubiquitous viral pathogens of cattle. These viruses exist as one of two biotypes, cytopathic and noncytopathic, based on the ability to induce cytopathic effect in cell culture. The noncytopathic biotypes are able to establish nonapparent, persistent infect...

  8. Hypothesis for heritable, anti-viral immunity in crustaceans and insects

    Microsoft Academic Search

    Timothy W Flegel; Klong Luang

    2009-01-01

    BACKGROUND: It is known that crustaceans and insects can persistently carry one or more viral pathogens at low levels, without signs of disease. They may transmit them to their offspring or to naïve individuals, often with lethal consequences. The underlying molecular mechanisms have not been elucidated, but the process has been called viral accommodation. Since tolerance to one virus does

  9. Rapid detection of bovine viral diarrhea virus as surrogate of bioterrorism agents

    Microsoft Academic Search

    Zarini Muhammad-Tahir; Evangelyn C. Alocilja; Daniel L. Grooms

    2005-01-01

    Bovine viral diarrhea virus (BVDV) is a major pathogen of cattle that is chosen as a model for select agents associated with agricultural bioterrorism, such as foot and mouth disease virus. Bovine viral diarrhea virus causes early embryonic death, abortion, respiratory problems, and immune system dysfunction in cattle throughout the world. Due to the insidious nature and economic loses from

  10. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG).

    PubMed

    Chen, Robert T; Carbery, Baevin; Mac, Lisa; Berns, Kenneth I; Chapman, Louisa; Condit, Richard C; Excler, Jean-Louis; Gurwith, Marc; Hendry, Michael; Khan, Arifa S; Khuri-Bulos, Najwa; Klug, Bettina; Robertson, James S; Seligman, Stephen J; Sheets, Rebecca; Williamson, Anna-Lise

    2015-01-01

    Recombinant viral vectors provide an effective means for heterologous antigen expression in vivo and thus represent promising platforms for developing novel vaccines against human pathogens from Ebola to tuberculosis. An increasing number of candidate viral vector vaccines are entering human clinical trials. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to improve our ability to anticipate potential safety issues and meaningfully assess or interpret safety data, thereby facilitating greater public acceptance when licensed. PMID:25305565

  11. Viral Hepatitis Transmission in Ambulatory Health Care Settings

    Microsoft Academic Search

    I. T. Williams; J. F. Perz; B. P. Bell

    2004-01-01

    In the United States, transmission of viral hepatitis from health care-related exposures is uncommon and primarily recognized in the context of outbreaks. Transmission is typically associated with unsafe injection practices, as exemplified by several recent outbreaks that occurred in ambulatory health care settings. To prevent transmission of bloodborne pathogens, health care workers must adhere to standard precautions and follow fundamental

  12. AndreGratia: A Forerunner in Microbial and Viral Genetics

    Microsoft Academic Search

    James F. Crow; William F. Dove; Jean-Pierre Gratia

    riophages in connection with the study of viruses and cell biology; and (e) unknown aspects of lysogeny and When people spoke of microbes in the early 1900s, colicinogeny described long ago and possibly connected they were thinking almost exclusively of bacterial (and with new findings on imprinting in bacteria. viral) pathogens affecting humans. Of course, Antonie Microbiology has undeniably played

  13. Genomics-Bioinformatics Day on "Pathogens, Molecular Evolution and Bionformatics" October Thursday 9th 2003

    E-print Network

    Goldschmidt, Christina

    Genomics-Bioinformatics Day on "Pathogens, Molecular Evolution and Bionformatics" October Thursday continue this with a day arranged by Jotun Hein and Eddie Holmes with the focus on Pathogens, Molecular Problems for Microbial Pathogens" Hein: "Models of viral evolution involving multiple constraints" Drummond

  14. 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

  15. Haemorrhagic Fevers, Viral

    MedlinePLUS

    ... haemorrhagic fevers), Filoviridae (Ebola and Marburg) and Flaviviridae (yellow fever, dengue, Omsk haemorrhagic fever, Kyasanur forest disease). Ebola ... topics Dengue Disease outbreaks Infectious diseases Tropical diseases Yellow fever You are here: Health topics Haemorrhagic fevers, Viral ...

  16. Immigration and viral hepatitis.

    PubMed

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J; Janssen, Harry L A

    2015-08-01

    WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500million, with an annual mortality rate of up to 1.3million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants. PMID:25962882

  17. Broad-spectrum antivirals against viral fusion.

    PubMed

    Vigant, Frederic; Santos, Nuno C; Lee, Benhur

    2015-07-01

    Effective antivirals have been developed against specific viruses, such as HIV, Hepatitis C virus and influenza virus. This 'one bug-one drug' approach to antiviral drug development can be successful, but it may be inadequate for responding to an increasing diversity of viruses that cause significant diseases in humans. The majority of viral pathogens that cause emerging and re-emerging infectious diseases are membrane-enveloped viruses, which require the fusion of viral and cell membranes for virus entry. Therefore, antivirals that target the membrane fusion process represent new paradigms for broad-spectrum antiviral discovery. In this Review, we discuss the mechanisms responsible for the fusion between virus and cell membranes and explore how broad-spectrum antivirals target this process to prevent virus entry. PMID:26075364

  18. The Structure of HLA-B8 Complexed to an Immunodominant Viral Determinant: Peptide-Induced Conformational Changes and a Mode of MHC Class I Dimerization1

    Microsoft Academic Search

    Lars Kjer-Nielsen; Craig S. Clements; Andrew G. Brooks; Anthony W. Purcell; Marcos R. Fontes; James McCluskey; Jamie Rossjohn

    EBV is a ubiquitous human pathogen that chronically infects up to 90% of the population. Persistent viral infection is charac- terized by latency and periods of viral replication that are kept in check by a strong antiviral CTL response. Despite the size of the EBV genome, CTL immunity focuses on only a few viral determinants but expands a large primary

  19. Characterization of the Viral Microbiome in Patients with Severe Lower Respiratory Tract Infections, Using Metagenomic Sequencing

    Microsoft Academic Search

    Fredrik Lysholm; Anna Wetterbom; Cecilia Lindau; Hamid Darban; Annelie Bjerkner; Kristina Fahlander; A. Michael Lindberg; Bengt Persson; Tobias Allander; Björn Andersson

    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

  20. The effects of bovine viral diarrhoea virus on cattle reproduction in relation to disease control

    Microsoft Academic Search

    M. D Fray; D. J Paton; S Alenius

    2000-01-01

    Bovine viral diarrhoea virus (BVDV) is a major reproductive pathogen in cattle. Infection of the bull can lead to a fall in semen quality and the isolation of infectious virus in the ejaculate, while infection in the cow leads to poor conception rates, abortions and congenital defects. BVDV also reduces the animal's resistance to other respiratory and enteric pathogens. The

  1. [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

  2. 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

  3. 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

  4. 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.

  5. 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.

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

    E-print Network

    Chen, Wilfred

    to 25 nm. The reduction in the ionic strength of the pH buffer solutions (i.e., 10 mM PBS to 10 mM PB significantly reduced by the buffer change. The optimum sensor showed excellent sensitivity with a low and upper transducer, such a minute perturbation leads to depletion/accumulation of charge carriers within the bulk

  7. Comparison of innate immune responses to pathogenic and putative non-pathogenic hantaviruses in vitro.

    PubMed

    Shim, So Hee; Park, Man-Seong; Moon, Sungsil; Park, Kwang Sook; Song, Jin-Won; Song, Ki-Joon; Baek, Luck Ju

    2011-09-01

    Hantaviruses are human pathogens that cause hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. The mechanisms accounting for the differences in virulence between pathogenic and non-pathogenic hantaviruses are not well known. We have examined the pathogenesis of different hantavirus groups by comparing the innate immune responses induced in the host cell following infection by pathogenic (Sin Nombre, Hantaan, and Seoul virus) and putative non-pathogenic (Prospect Hill, Tula, and Thottapalayam virus) hantaviruses. Pathogenic hantaviruses were found to replicate more efficiently in interferon-competent A549 cells than putative non-pathogenic hantaviruses. The former also suppressed the expression of the interferon-? and myxovirus resistance protein genes, while the transcription level of both genes increased rapidly within 24 h post-infection in the latter. In addition, the induction level of interferon correlated with the activation level of interferon regulatory factor-3. Taken together, these results suggest that the observed differences are correlated with viral pathogenesis and further indicate that pathogenic and putative non-pathogenic hantaviruses differ in terms of early interferon induction via activation of the interferon regulatory factor-3 in infected host cells. PMID:21820021

  8. BOVINE VIRAL DIARRHEA VIRUSES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) is an umbrella term for two species of viruses, BVDV1 and BVDV2, within the Pestivirus genus of the Flavivirus family. BVDV viruses are further subclassified as cytopathic and noncytopathic based on their activity in cultured epithelial cells. Noncytopathic BVDV p...

  9. Chronic viral diseases.

    PubMed Central

    Berris, B

    1986-01-01

    Until 20 years ago the only chronic viral diseases known were those considered to be confined to the nervous system. As a result of recent advances in epidemiology, molecular biology and immunology, new viral diseases have been recognized and their clinical features and pathogenesis elucidated. Chronic disease may result from infection with the hepatitis B and D viruses and whatever agent or agents cause hepatitis non-A, non-B, the herpesviruses, Epstein-Barr virus, cytomegalovirus and human T-lymphotropic virus type III. These diseases have common features, including long-term or even lifetime asymptomatic carriage, viremia, with virus free in the plasma or attached to circulating mononuclear cells, presence of virus in body secretions, irreversible tissue injury in target organs and oncogenic potential. New information on these diseases is reviewed. Other chronic diseases for which the cause is currently unknown may eventually prove to be due to viral infection. In addition, vaccines may be developed for prophylaxis of some chronic viral diseases and associated malignant diseases. PMID:3022903

  10. FastStats: Viral Hepatitis

    MedlinePLUS

    ... States, 2014, table 37 [PDF - 9.8 MB] Mortality Number of deaths: 8,157 Deaths per 100, ... in Health Data Interactive Viral Hepatitis Related Links Mortality data Centers for Disease Control and Prevention: Viral ...

  11. Low Plasma Human Immunodeficiency Virus Type 2 Viral Load Is Independent of Proviral Load: Low Virus Production In Vivo

    Microsoft Academic Search

    STEPHEN J. POPPER; ABDOULAYE DIENG SARR; AISSATOU GUEYE-NDIAYE; SOULEYMANE MBOUP; MYRON E. ESSEX; PHYLLIS J. KANKI

    2000-01-01

    Levels of virus in the plasma are closely related to the pathogenicity of human immunodeficiency virus type 1 (HIV-1). HIV-2 is much less pathogenic than HIV-1, and infection with HIV-2 leads to significantly lower plasma viral load. To identify the source of this difference, we measured both viral RNA and proviral DNA in matched samples from 34 HIV-2-infected individuals. Nearly

  12. Viral infection: Moving through complex and dynamic cell-membrane structures.

    PubMed

    Barroso-González, Jonathan; García-Expósito, Laura; Puigdomènech, Isabel; de Armas-Rillo, Laura; Machado, José-David; Blanco, Julià; Valenzuela-Fernández, Agustín

    2011-07-01

    Viruses have developed different survival strategies in host cells by crossing cell-membrane compartments, during different steps of their viral life cycle. In fact, the non-regenerative viral membrane of enveloped viruses needs to encounter the dynamic cell-host membrane, during early steps of the infection process, in which both membranes fuse, either at cell-surface or in an endocytic compartment, to promote viral entry and infection. Once inside the cell, many viruses accomplish their replication process through exploiting or modulating membrane traffic, and generating specialized compartments to assure viral replication, viral budding and spreading, which also serve to evade the immune responses against the pathogen. In this review, we have attempted to present some data that highlight the importance of membrane dynamics during viral entry and replicative processes, in order to understand how viruses use and move through different complex and dynamic cell-membrane structures and how they use them to persist. PMID:21966556

  13. 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

  14. A REVIEW OF PATHOGENS OF AGRICULTURAL AND HUMAN HEALTH INTEREST FOUND IN CANADA GEESE

    Microsoft Academic Search

    Larry Clark

    2003-01-01

    The roles that waterfowl in general, and Canada geese in particular, have in the dissemination and transmission of viral and bacterial diseases of human or agricultural importance are covered in this review. In addition to the biological information about the etiology of the disease, economic impacts and zoonotic potential of viral and bacterial pathogens are considered. In most cases existing

  15. Viral infections of the newborn.

    PubMed

    Strodtbeck, F

    1995-09-01

    Viral infections of the newborn result in significant morbidity and mortality each year. The fetus and newborn are particularly vulnerable to viral infection. The range of expression may vary from no clinical disease to devastating illness and infection occurring before, during, or after birth. Nursing management is determined by the specific viral infection, the severity of the illness, and the unique conditions of the newborn and his/her family. Promising new therapies are on the horizon that may lessen the severity of viral disease. Until such time, the major thrusts of management of neonatal viral disease are prevention of infection and supportive care for the acutely ill newborn. PMID:7500196

  16. 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

  17. 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

  18. Viral Hepatitis D

    Microsoft Academic Search

    John M. Taylor

    \\u000a Viral hepatitis D, also known as hepatitis delta virus (HDV), was first discovered by Mario Rizzetto in 1977, in a study of\\u000a Italian patients infected with hepatitis B virus (HBV), who seemed to have a more damaging liver disease. For more information\\u000a on HBV, please see Chap. 37. In liver biopsies from such patients, a serum antibody detected a novel

  19. IRGM in autophagy and viral infections

    PubMed Central

    Petkova, Denitsa S.; Viret, Christophe; Faure, Mathias

    2013-01-01

    Autophagy is a cell autonomous process allowing each individual cell to fight intracellular pathogens. Autophagy can destroy pathogens within the cytosol, and can elicit innate and adaptive immune responses against microorganisms. Nevertheless, numerous pathogens have developed molecular strategies enabling them to avoid or even exploit autophagy for their own benefit. IRGM (immunity-related GTPase family M) is a human protein recently highlighted for its contribution to autophagy upon infections. The physical association of IRGM with mitochondria and different autophagy-regulating proteins, ATG5, ATG10, SH3GLB1, and LC3, contribute to explain how IRGM could regulate autophagy. Whereas IRGM is involved in autophagy-mediated immunity against bacteria, certain viruses seem to have developed strategies to manipulate autophagy through the selective targeting of this protein. Furthermore, irgm variants are linked to infection-associated human pathologies such as the inflammatory Crohn’s disease. Here, we discuss how IRGM might contribute to human autophagy upon viral infection, and why its targeting might be beneficial to virus replication. PMID:23335927

  20. Informing the front line about common respiratory viral epidemics.

    PubMed

    Gesteland, Per H; Samore, Matthew H; Pavia, Andrew T; Srivastava, Rajendu; Korgenski, Kent; Gerber, Kristine; Daly, Judy A; Mundorff, Michael B; Rolfs, Robert T; James, Brent C; Byington, Carrie L

    2007-01-01

    The nature of clinical medicine is to focus on individuals rather than the populations from which they originate. This orientation can be problematic in the context of acute healthcare delivery during routine winter outbreaks of viral respiratory disease where an individuals likelihood of viral infection depends on knowledge of local disease incidence. The level of interest in and perceived utility of community and regional infection data for front line clinicians providing acute care is unclear. Based on input from clinicians, we developed an automated analysis and reporting system that delivers pathogen-specific epidemic curves derived from a viral panel that tests for influenza, RSV, adenovirus, parainfluenza and human metapneumovirus. Surveillance summaries were actively e-mailed to clinicians practicing in emergency, urgent and primary care settings and posted on a web site for passive consumption. We demonstrated the feasibility and sustainability of a system that provides both timely and clinically useful surveillance information. PMID:18693841

  1. Coagulation, protease-activated receptors, and viral myocarditis.

    PubMed

    Antoniak, Silvio; Mackman, Nigel

    2014-03-01

    The coagulation protease cascade plays an essential role in hemostasis. In addition, a clot contributes to host defense by limiting the spread of pathogens. Coagulation proteases induce intracellular signaling by cleavage of cell surface receptors called protease-activated receptors (PARs). These receptors allow cells to sense changes in the extracellular environment, such as infection. Viruses activate the coagulation cascade by inducing tissue factor expression and by disrupting the endothelium. Virus infection of the heart can cause myocarditis, cardiac remodeling, and heart failure. A recent study using a mouse model have shown that tissue factor, thrombin, and PAR-1 signaling all positively regulate the innate immune during viral myocarditis. In contrast, PAR-2 signaling was found to inhibit interferon-? expression and the innate immune response. These observations suggest that anticoagulants may impair the innate immune response to viral infection and that inhibition of PAR-2 may be a new strategy to reduce viral myocarditis. PMID:24203054

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

    PubMed

    George, Dylan B; Webb, Colleen T; Farnsworth, Matthew L; O'Shea, Thomas J; Bowen, Richard A; Smith, David L; Stanley, Thomas R; Ellison, Laura E; Rupprecht, Charles E

    2011-06-21

    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. PMID:21646516

  3. 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...

  4. Fluorescent primer-based in vitro transcription system of viral RNA-dependent RNA polymerases.

    PubMed

    Wang, Qiang; Weng, Leiyun; Jiang, Hongbing; Zhang, Shijian; Toyoda, Tetsuya

    2013-02-15

    Viral infection is a leading cause of disease and death. Although vaccines are the most effective method of controlling viral infections, antiviral drugs are also important. Here, we established an in vitro transcription system by using fluorescein isothiocyanate-conjugated primers for RNA polymerases of viruses that are important disease-causing human pathogens (influenza, hepatitis C, Japanese encephalitis viruses, and enterovirus 71). This technology will allow us to analyze RNA polymerase activity without using radioisotopes. PMID:23103398

  5. 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) ...

  6. 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 ...

  7. Systems for eliminating pathogens from exhaust air of animal houses

    Microsoft Academic Search

    A. J. A. Aarnink; W. J. M. Landman; R. W. Melse; Huynh Thi Thanh Thuy

    2005-01-01

    Recent outbreaks of highly infectious viral diseases like swine fever and avian influenza in The Netherlands have shown that despite extensive bio-security measures aiming at minimizing physical contacts between farms, disease spread could not be halted. Dust in exhaust air from swine and chicken houses may provide a favorable environment in which these viruses and other pathogenic microorganisms can survive

  8. Viral noncoding RNAs: more surprises.

    PubMed

    Tycowski, Kazimierz T; Guo, Yang Eric; Lee, Nara; Moss, Walter N; Vallery, Tenaya K; Xie, Mingyi; Steitz, Joan A

    2015-03-15

    Eukaryotic cells produce several classes of long and small noncoding RNA (ncRNA). Many DNA and RNA viruses synthesize their own ncRNAs. Like their host counterparts, viral ncRNAs associate with proteins that are essential for their stability, function, or both. Diverse biological roles--including the regulation of viral replication, viral persistence, host immune evasion, and cellular transformation--have been ascribed to viral ncRNAs. In this review, we focus on the multitude of functions played by ncRNAs produced by animal viruses. We also discuss their biogenesis and mechanisms of action. PMID:25792595

  9. Viral hepatitis in Bucharest.

    PubMed Central

    Paquet, C.; Babes, V. T.; Drucker, J.; Sénémaud, B.; Dobrescu, A.

    1993-01-01

    A seroprevalence survey of viral hepatitis was conducted in Bucharest, Romania, between April and July 1990 on a systematic sample of 1355 persons drawn from the general population and groups at higher risk of infection. Sera were tested for hepatitis A, B, and C (HAV, HBV and HCV, resp.) markers using an enzyme-linked immunosorbent assay (ELISA) method. The prevalences of HAV and HBV markers were high in all groups. A total of 47% of the adults from the general population and 39.8% of the children aged 0-16 years had at least one HBV marker. Of the pregnant women 7.8% were positive for hepatitis B surface antigen. Among infants (0-3 years of age) living in orphanages, the prevalence of at least one HBV marker was 54.6%. The findings also confirmed that HCV was circulating in Romania. The results are consistent with national surveillance data and confirm that viral hepatitis is a major public health problem in Romania. Preventive measures will have to include HBV immunization of infants, with an appropriately targeted immunization strategy being determined through further epidemiological studies. PMID:8313496

  10. Viral veterinary vaccines.

    PubMed

    Pastoret, P P; Falize, F

    1999-01-01

    The value of animal models for assessing the quality of veterinary viral vaccines is not to be despised, particularly since one has access to target animal models which are often more relevant than those in the laboratory, especially for challenge/protection studies. Immune protection involves complex immunological phenomena and processes. It is particularly true whenever cellular immunity plays a crucial role because it is still easier to measure antibody responses than cellular ones in vitro. Nevertheless the trend is to replace animal models by in vitro system whenever possible. The problem of the replacement of in vivo by in vitro models is further impeded in Europe by the necessity to comply with Pharmacopoeia monographs where the use of laboratory and/or target animals is often requested. Recent advances have been made with several inactivated viral vaccines such as equine influenza, where strain variability poses a special problem, or rabies, for which the use of inactivated instead of attenuated vaccines for vaccination of animals became compulsory in many countries. PMID:10566778

  11. 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

  12. Viral Diseases in Zebrafish: What Is Known and Unknown

    PubMed Central

    Crim, Marcus J.; Riley, Lela K.

    2013-01-01

    Naturally occurring viral infections have the potential to introduce confounding variability that leads to invalid and misinterpreted data. Whereas the viral diseases of research rodents are well characterized and closely monitored, no naturally occurring viral infections have been characterized for the laboratory zebrafish (Danio rerio), an increasingly important biomedical research model. Despite the ignorance about naturally occurring zebrafish viruses, zebrafish models are rapidly expanding in areas of biomedical research where the confounding effects of unknown infectious agents present a serious concern. In addition, many zebrafish research colonies remain linked to the ornamental (pet) zebrafish trade, which can contribute to the introduction of new pathogens into research colonies, whereas mice used for research are purpose bred, with no introduction of new mice from the pet industry. Identification, characterization, and monitoring of naturally occurring viruses in zebrafish are crucial to the improvement of zebrafish health, the reduction of unwanted variability, and the continued development of the zebrafish as a model organism. This article addresses the importance of identifying and characterizing the viral diseases of zebrafish as the scope of zebrafish models expands into new research areas and also briefly addresses zebrafish susceptibility to experimental viral infection and the utility of the zebrafish as an infection and immunology model. PMID:23382345

  13. 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

  14. NK Cell Subset Redistribution during the Course of Viral Infections

    PubMed Central

    Lugli, Enrico; Marcenaro, Emanuela; Mavilio, Domenico

    2014-01-01

    Natural killer (NK) cells are important effectors of innate immunity that play a critical role in the control of human viral infections. Indeed, given their capability to directly recognize virally infected cells without the need of specific antigen presentation, NK cells are on the first line of defense against these invading pathogens. By establishing cellular networks with a variety of cell types such as dendritic cells, NK cells can also amplify anti-viral adaptive immune responses. In turn, viruses evolved and developed several mechanisms to evade NK cell-mediated immune activity. It has been reported that certain viral diseases, including human immunodeficiency virus-1 as well as human cytomegalovirus infections, are associated with a pathologic redistribution of NK cell subsets in the peripheral blood. In particular, it has been observed the expansion of unconventional CD56neg NK cells, whose effector functions are significantly impaired as compared to that of conventional CD56pos NK cells. In this review, we address the impact of these two chronic viral infections on the functional and phenotypic perturbations of human NK cell compartment. PMID:25177322

  15. Viral infection of engrafted human islets leads to diabetes.

    PubMed

    Gallagher, Glen R; Brehm, Michael A; Finberg, Robert W; Barton, Bruce A; Shultz, Leonard D; Greiner, Dale L; Bortell, Rita; Wang, Jennifer P

    2015-04-01

    Type 1 diabetes (T1D) is characterized by the destruction of the insulin-producing ?-cells of pancreatic islets. Genetic and environmental factors both contribute to T1D development. Viral infection with enteroviruses is a suspected trigger for T1D, but a causal role remains unproven and controversial. Studies in animals are problematic because of species-specific differences in host cell susceptibility and immune responses to candidate viral pathogens such as coxsackievirus B (CVB). In order to resolve the controversial role of viruses in human T1D, we developed a viral infection model in immunodeficient mice bearing human islet grafts. Hyperglycemia was induced in mice by specific ablation of native ?-cells. Human islets, which are naturally susceptible to CVB infection, were transplanted to restore normoglycemia. Transplanted mice were infected with CVB4 and monitored for hyperglycemia. Forty-seven percent of CVB4-infected mice developed hyperglycemia. Human islet grafts from infected mice contained viral RNA, expressed viral protein, and had reduced insulin levels compared with grafts from uninfected mice. Human-specific gene expression profiles in grafts from infected mice revealed the induction of multiple interferon-stimulated genes. Thus, human islets can become severely dysfunctional with diminished insulin production after CVB infection of ?-cells, resulting in diabetes. PMID:25392246

  16. Viral meningitis and encephalitis: Traditional and emerging viral agents

    Microsoft Academic Search

    José R. Romero; Jason G. Newland

    2003-01-01

    In the United States, the annual number of central nervous system (CNS) infections that occur as a result of viral agents far exceeds that of infections caused by bacteria, yeast, molds, and protozoa combined. The recent incursion of West Nile virus (WNV) into North America has led to a dramatic change in the incidence and epidemiology of summer-associated viral CNS

  17. Staying Alive: Cell Death in Anti-Viral Immunity

    PubMed Central

    Upton, Jason W.; Chan, Francis Ka-Ming

    2014-01-01

    Programmed cell death is an integral part of host defense against invading intracellular pathogens. Apoptosis, programmed necrosis, and pyroptosis each serve to limit pathogen replication in infected cells, while simultaneously promoting the inflammatory and innate responses that shape effective long-term host immunity. The importance of carefully regulated cell death is evident in the spectrum of inflammatory and autoimmune disorders caused by defects in these pathways. Moreover, many viruses encode inhibitors of programmed cell death to subvert these host responses during infection, thereby facilitating their own replication and persistence. Thus, as both virus and cell vie for control of these pathways, the battle for survival has shaped a complex host-pathogen interaction. This review will discuss the multifaceted role programmed cell death plays in maintaining the immune system and its critical function in host defense, with a special emphasis on viral infections. PMID:24766891

  18. Deep Sequencing to Identify the Causes of Viral Encephalitis

    PubMed Central

    Chan, Benjamin K.; Wilson, Theodore; Fischer, Kael F.; Kriesel, John D.

    2014-01-01

    Deep sequencing allows for a rapid, accurate characterization of microbial DNA and RNA sequences in many types of samples. Deep sequencing (also called next generation sequencing or NGS) is being developed to assist with the diagnosis of a wide variety of infectious diseases. In this study, seven frozen brain samples from deceased subjects with recent encephalitis were investigated. RNA from each sample was extracted, randomly reverse transcribed and sequenced. The sequence analysis was performed in a blinded fashion and confirmed with pathogen-specific PCR. This analysis successfully identified measles virus sequences in two brain samples and herpes simplex virus type-1 sequences in three brain samples. No pathogen was identified in the other two brain specimens. These results were concordant with pathogen-specific PCR and partially concordant with prior neuropathological examinations, demonstrating that deep sequencing can accurately identify viral infections in frozen brain tissue. PMID:24699691

  19. 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

  20. The role of autophagy in intracellular pathogen nutrient acquisition

    PubMed Central

    Steele, Shaun; Brunton, Jason; Kawula, Thomas

    2015-01-01

    Following entry into host cells intracellular pathogens must simultaneously evade innate host defense mechanisms and acquire energy and anabolic substrates from the nutrient-limited intracellular environment. Most of the potential intracellular nutrient sources are stored within complex macromolecules that are not immediately accessible by intracellular pathogens. To obtain nutrients for proliferation, intracellular pathogens must compete with the host cell for newly-imported simple nutrients or degrade host nutrient storage structures into their constituent components (fatty acids, carbohydrates, and amino acids). It is becoming increasingly evident that intracellular pathogens have evolved a wide variety of strategies to accomplish this task. One recurrent microbial strategy is to exploit host degradative processes that break down host macromolecules into simple nutrients that the microbe can use. Herein we focus on how a subset of bacterial, viral, and eukaryotic pathogens leverage the host process of autophagy to acquire nutrients that support their growth within infected cells.

  1. 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

  2. Oral Manifestations of Viral Diseases

    Microsoft Academic Search

    Denis P. Lynch

    other chapters dealing with specific viruses. Second, the clinical oral manifestations of such infections are described, with an emphasis on the differential diagnosis of specific oral viral lesions. Third, the methods used in the diagno- sis of oral viral lesions are presented. Fourth, a summary of current therapeutic management strategies is presented, along with their relation- ship to long-term prognosis.

  3. 4 Viral serology and detection

    Microsoft Academic Search

    Shaun Greer; Graeme J. M. Alexander

    1995-01-01

    Viral detection is an important part of clinical hepatology. For many years practical clinical tests have been serological but recently newer molecular techniques have become available for virus detection, although these have yet to become routine and some, such as PCR of viral nucleic acid in blood or tissue are not yet consistently reliable. Serology remains the mainstay at present

  4. 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

  5. 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...

  6. 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

  7. 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. PMID:26038515

  8. The hepatitis C virus Core protein is a potent nucleic acid chaperone that directs dimerization of the viral (+) strand RNA in vitro

    Microsoft Academic Search

    Gael Cristofari; Roland Ivanyi-Nagy; Caroline Gabus; Steeve Boulant; Jean-Pierre Lavergne; Francois Penin; Jean-Luc Darlix

    2004-01-01

    The hepatitis C virus (HCV) is an important human pathogen causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV is an enveloped virus with a positive-sense, single-stranded RNA genome encoding a single polyprotein that is processed to generate viral proteins. Several hundred molecules of the structural Core protein are thought to coat the genome in the viral particle, as do

  9. Cellular visualization of macrophage pyroptosis and interleukin-1? release in a viral hemorrhagic infection in zebrafish larvae.

    PubMed

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

    2014-10-01

    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

  10. Sphingolipids in viral infection.

    PubMed

    Schneider-Schaulies, Jürgen; Schneider-Schaulies, Sibylle

    2015-06-01

    Viruses exploit membranes and their components such as sphingolipids in all steps of their life cycle including attachment and membrane fusion, intracellular transport, replication, protein sorting and budding. Examples for sphingolipid-dependent virus entry are found for: human immunodeficiency virus (HIV), which besides its protein receptors also interacts with glycosphingolipids (GSLs); rhinovirus, which promotes the formation of ceramide-enriched platforms and endocytosis; or measles virus (MV), which induces the surface expression of its own receptor CD150 via activation of sphingomyelinases (SMases). While SMase activation was implicated in Ebola virus (EBOV) attachment, the virus utilizes the cholesterol transporter Niemann-Pick C protein 1 (NPC1) as 'intracellular' entry receptor after uptake into endosomes. Differential activities of SMases also affect the intracellular milieu required for virus replication. Sindbis virus (SINV), for example, replicates better in cells lacking acid SMase (ASMase). Defined lipid compositions of viral assembly and budding sites influence virus release and infectivity, as found for hepatitis C virus (HCV) or HIV. And finally, viruses manipulate cellular signaling and the sphingolipid metabolism to their advantage, as for example influenza A virus (IAV), which activates sphingosine kinase 1 and the transcription factor NF-?B. PMID:25525752

  11. Bovine viral diarrhea virus infection alters global transcription profiles in bovine endothelial cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea viruses (BVDV) are significant pathogens of cattle worldwide. These viruses exist in both non-cytopathic and cytopathic biotypes. Non-cytopathic BVDV can establish persistent lifelong infections in cattle and are a frequent contaminant of biological reagents such as cell cultur...

  12. Differential effects of bovine viral diarrhoea virus on monocytes and dendritic cells

    Microsoft Academic Search

    E. J. Glew; B. V. Carr; L. S. Brackenbury; J. C. Hope; B. Charleston; C. J. Howard

    2003-01-01

    Various pathogens have been shown to infect antigen-presenting cells and affect their capacity to interact with and stimulate T-cell responses. We have used an antigenically identical pair of non- cytopathic (ncp) and cytopathic (cp) bovine viral diarrhoea virus (BVDV) isolates to determine how the two biotypes affect monocyte and dendritic cell (DC) function. We have shown that monocytes and DCs

  13. A Viral-Human Interactome Based on Structural Motif-Domain Interactions Captures the Human Infectome

    PubMed Central

    Guo, Xianwu; Rodríguez-Pérez, Mario A.

    2013-01-01

    Protein interactions between a pathogen and its host are fundamental in the establishment of the pathogen and underline the infection mechanism. In the present work, we developed a single predictive model for building a host-viral interactome based on the identification of structural descriptors from motif-domain interactions of protein complexes deposited in the Protein Data Bank (PDB). The structural descriptors were used for searching, in a database of protein sequences of human and five clinically important viruses; therefore, viral and human proteins sharing a descriptor were predicted as interacting proteins. The analysis of the host-viral interactome allowed to identify a set of new interactions that further explain molecular mechanism associated with viral infections and showed that it was able to capture human proteins already associated to viral infections (human infectome) and non-infectious diseases (human diseasome). The analysis of human proteins targeted by viral proteins in the context of a human interactome showed that their neighbors are enriched in proteins reported with differential expression under infection and disease conditions. It is expected that the findings of this work will contribute to the development of systems biology for infectious diseases, and help guide the rational identification and prioritization of novel drug targets. PMID:23951184

  14. 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.

  15. Gene therapy for viral hepatitis.

    PubMed

    Gonzalez-Aseguinolaza, Gloria; Crettaz, Julien; Ochoa, Laura; Otano, Itziar; Aldabe, Rafael; Paneda, Astrid

    2006-12-01

    Hepatitis B and C infections are two of the most prevalent viral diseases in the world. Existing therapies against chronic viral hepatitis are far from satisfactory due to low response rates, undesirable side effects and selection of resistant viral strains. Therefore, new therapeutic approaches are urgently needed. This review, after briefly summarising the in vitro and in vivo systems for the study of both diseases and the genetic vehicles commonly used for liver gene transfer, examines the existing status of gene therapy-based antiviral strategies that have been employed to prevent, eliminate or reduce viral infection. In particular, the authors focus on the results obtained in clinical trials and experimental clinically relevant animal models. PMID:17223736

  16. Neuroanatomy goes viral!

    PubMed Central

    Nassi, Jonathan J.; Cepko, Constance L.; Born, Richard T.; Beier, Kevin T.

    2015-01-01

    The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist’s toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic spread, and extending the range of species that can be studied.

  17. 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

  18. Current challenges in viral safety and extraneous agent testing.

    PubMed

    Mackay, David; Kriz, Nikolaus

    2010-05-01

    There are three principal elements related to viral safety in the context of immunological veterinary medicinal products: the presence of extraneous agents in either raw material used for production or in the finished product, residual pathogenicity of live viruses used as active ingredients, and incomplete inactivation of inactivated viruses used as active ingredients. Although the approach to controlling these areas of risk has not substantially changed in the recent past, a number of events, combined with advances in science and changes in the regulatory approach, make it timely to review the requirements in this area. This article reviews the major areas of change and progress with respect to the viral safety of immunological veterinary medicinal products and identifies current challenges from the perspectives of both industry and regulators. PMID:20338787

  19. Commentary on the Regulation of Viral Proteins in Autophagy Process

    PubMed Central

    Cheng, Ching-Yuan; Chi, Pei-I

    2014-01-01

    The ability to subvert intracellular antiviral defenses is necessary for virus to survive as its replication occurs only in the host cells. Viruses have to modulate cellular processes and antiviral mechanisms to their own advantage during the entire virus life cycle. Autophagy plays important roles in cell regulation. Its function is not only to catabolize aggregate proteins and damaged organelles for recycling but also to serve as innate immunity to remove intracellular pathogenic elements such as viruses. Nevertheless, some viruses have evolved to negatively regulate autophagy by inhibiting its formation. Even more, some viruses have employed autophagy to benefit their replication. To date, there are more and more growing evidences uncovering the functions of many viral proteins to regulate autophagy through different cellular pathways. In this review, we will discuss the relationship between viruses and autophagy and summarize the current knowledge on the functions of viral proteins contributing to affect autophagy process. PMID:24734254

  20. GeMInA, Genomic Metadata for Infectious Agents, a geospatial surveillance pathogen database

    PubMed Central

    Schriml, Lynn M.; Arze, Cesar; Nadendla, Suvarna; Ganapathy, Anu; Felix, Victor; Mahurkar, Anup; Phillippy, Katherine; Gussman, Aaron; Angiuoli, Sam; Ghedin, Elodie; White, Owen; Hall, Neil

    2010-01-01

    The Gemina system (http://gemina.igs.umaryland.edu) identifies, standardizes and integrates the outbreak metadata for the breadth of NIAID category A–C viral and bacterial pathogens, thereby providing an investigative and surveillance tool describing the Who [Host], What [Disease, Symptom], When [Date], Where [Location] and How [Pathogen, Environmental Source, Reservoir, Transmission Method] for each pathogen. The Gemina database will provide a greater understanding of the interactions of viral and bacterial pathogens with their hosts and infectious diseases through in-depth literature text-mining, integrated outbreak metadata, outbreak surveillance tools, extensive ontology development, metadata curation and representative genomic sequence identification and standards development. The Gemina web interface provides metadata selection and retrieval of a pathogen's; Infection Systems (Pathogen, Host, Disease, Transmission Method and Anatomy) and Incidents (Location and Date) along with a hosts Age and Gender. The Gemina system provides an integrated investigative and geospatial surveillance system connecting pathogens, pathogen products and disease anchored on the taxonomic ID of the pathogen and host to identify the breadth of hosts and diseases known for these pathogens, to identify the extent of outbreak locations, and to identify unique genomic regions with the DNA Signature Insignia Detection Tool. PMID:19850722

  1. Systems Integration of Biodefense Omics Data for Analysis of Pathogen-Host Interactions and Identification of Potential Targets

    Microsoft Academic Search

    Peter B. McGarvey; Hongzhan Huang; Raja Mazumder; Jian Zhang; Yongxing Chen; Chengdong Zhang; Stephen Cammer; Rebecca Will; Margie Odle; Bruno Sobral; Margaret Moore; Cathy H. Wu; Jörg Hoheisel

    2009-01-01

    The NIAID (National Institute for Allergy and Infectious Diseases) Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents.

  2. 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

  3. Viral infections and bovine mastitis: a review.

    PubMed

    Wellenberg, G J; van der Poel, W H M; Van Oirschot, J T

    2002-08-01

    This review deals with the role of viruses in the aetiology of bovine mastitis. Bovine herpesvirus 1, bovine herpesvirus 4, foot-and-mouth disease virus, and parainfluenza 3 virus have been isolated from milk from cows with clinical mastitis. Intramammary inoculations of bovine herpesvirus 1 or parainfluenza 3 virus-induced clinical mastitis, while an intramammary inoculation of foot-and-mouth disease virus resulted in necrosis of the mammary gland. Subclinical mastitis has been induced after a simultaneous intramammary and intranasal inoculation of lactating cows with bovine herpesvirus 4. Bovine leukaemia virus has been detected in mammary tissue of cows with subclinical mastitis, but whether this virus was able to induce bovine mastitis has not been reported. Bovine herpesvirus 2, vaccinia, cowpox, pseudocowpox, vesicular stomatitis, foot-and-mouth disease viruses, and bovine papillomaviruses can play an indirect role in the aetiology of bovine mastitis. These viruses can induce teat lesions, for instance in the ductus papillaris, which result in a reduction of the natural defence mechanisms of the udder and indirectly in bovine mastitis due to bacterial pathogens. Bovine herpesvirus 1, bovine viral diarrhoea virus, bovine immunodeficiency virus, and bovine leukaemia virus infections may play an indirect role in bovine mastitis, due to their immunosuppressive properties. But, more research is warranted to underline their indirect role in bovine mastitis. We conclude that viral infections can play a direct or indirect role in the aetiology of bovine mastitis; therefore, their importance in the aetiology of bovine mastitis and their economical impact needs further attention. PMID:12119136

  4. Structure, function and physiological consequences of virally encoded chemokine seven transmembrane receptors

    PubMed Central

    Rosenkilde, M M; Smit, M J; Waldhoer, M

    2008-01-01

    A number of human and animal herpes viruses encode G-protein coupled receptors with seven transmembrane (7TM) segments—most of which are clearly related to human chemokine receptors. It appears, that these receptors are used by the virus for immune evasion, cellular transformation, tissue targeting, and possibly for cell entry. In addition, many virally-encoded chemokine 7TM receptors have been suggested to be causally involved in pathogenic phenotypes like Kaposi sarcoma, atherosclerosis, HIV-infection and tumour development. The role of these receptors during the viral life cycle and in viral pathogenesis is still poorly understood. Here we focus on the current knowledge of structure, function and trafficking patterns of virally encoded chemokine receptors and further address the putative roles of these receptors in virus survival and host -cell and/or -immune system modulation. Finally, we highlight the emerging impact of these receptor on virus-mediated diseases. PMID:18204488

  5. Viral Membrane Channels: Role and Function in the Virus Life Cycle.

    PubMed

    Sze, ChingWooen; Tan, Yee-Joo

    2015-01-01

    Viroporins are small, hydrophobic trans-membrane viral proteins that oligomerize to form hydrophilic pores in the host cell membranes. These proteins are crucial for the pathogenicity and replication of viruses as they aid in various stages of the viral life cycle, from genome uncoating to viral release. In addition, the ion channel activity of viroporin causes disruption in the cellular ion homeostasis, in particular the calcium ion. Fluctuation in the calcium level triggers the activation of the host defensive programmed cell death pathways as well as the inflammasome, which in turn are being subverted for the viruses' replication benefits. This review article summarizes recent developments in the functional investigation of viroporins from various viruses and their contributions to viral replication and virulence. PMID:26110585

  6. 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. PMID:25897250

  7. Viral (hepatitis C virus, hepatitis B virus, HIV) persistence and immune homeostasis.

    PubMed

    Zhou, Yun; Zhang, Ying; Moorman, Jonathan P; Yao, Zhi Q; Jia, Zhan S

    2014-11-01

    Immune homeostasis is a host characteristic that maintains biological balance within a host. Humans have evolved many host defence mechanisms that ensure the survival of individuals upon encountering a pathogenic infection, with recovery or persistence from a viral infection being determined by both viral factors and host immunity. Chronic viral infections, such as hepatitis B virus, hepatitis C virus and HIV, often result in chronic fluctuating viraemia in the face of host cellular and humoral immune responses, which are dysregulated by multi-faceted mechanisms that are incompletely understood. This review attempts to illuminate the mechanisms involved in this process, focusing on immune homeostasis in the setting of persistent viral infection from the aspects of host defence mechanism, including interferon-stimulated genes, apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3), autophagy and interactions of various immune cells, cytokines and regulatory molecules. PMID:24965611

  8. Viral Membrane Channels: Role and Function in the Virus Life Cycle

    PubMed Central

    Sze, Ching Wooen; Tan, Yee-Joo

    2015-01-01

    Viroporins are small, hydrophobic trans-membrane viral proteins that oligomerize to form hydrophilic pores in the host cell membranes. These proteins are crucial for the pathogenicity and replication of viruses as they aid in various stages of the viral life cycle, from genome uncoating to viral release. In addition, the ion channel activity of viroporin causes disruption in the cellular ion homeostasis, in particular the calcium ion. Fluctuation in the calcium level triggers the activation of the host defensive programmed cell death pathways as well as the inflammasome, which in turn are being subverted for the viruses’ replication benefits. This review article summarizes recent developments in the functional investigation of viroporins from various viruses and their contributions to viral replication and virulence. PMID:26110585

  9. 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

  10. Mechanisms of bacterial pathogenicity

    PubMed Central

    Wilson, J; Schurr, M; LeBlanc, C; Ramamurthy, R; Buchanan, K; Nickerson, C

    2002-01-01

    Pathogenic bacteria utilise a number of mechanisms to cause disease in human hosts. Bacterial pathogens express a wide range of molecules that bind host cell targets to facilitate a variety of different host responses. The molecular strategies used by bacteria to interact with the host can be unique to specific pathogens or conserved across several different species. A key to fighting bacterial disease is the identification and characterisation of all these different strategies. The availability of complete genome sequences for several bacterial pathogens coupled with bioinformatics will lead to significant advances toward this goal. PMID:11930024

  11. [An update on viral diseases of the dog and cat].

    PubMed

    Bodewes, R; Egberink, H F

    2009-04-15

    In this review, recent developments in the field of viral diseases of the dog and the cat are discussed. In the dog, infection with the coronavirus type 2 is associated with respiratory signs, while infection of a highly pathogenic strain of the coronavirus type 1 has been identified as the cause of mortality in puppies. A new strain of the canine parvovirus is identified, from which the pathogenicity is not yet completely clarified. Infection with West Nile virus is associated with progressive neurological disease and subclinical infections in dogs. Infection with equine influenza A (H3N8) or a highly related influenza virus can cause severe respiratory disease and mortality in greyhounds and other dogs. Infection with avian influenza A (H5N1) can cause disease and mortality in cats and is mostly subclinical in dogs. A number of outbreaks of highly virulent strains of the calicivirus in cats have been described. PMID:19462619

  12. 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.

  13. High Viral Fitness during Acute HIV-1 Infection

    PubMed Central

    Arnott, Alicia; Jardine, Darren; Wilson, Kim; Gorry, Paul R.; Merlin, Kate; Grey, Patricia; Law, Matthew G.; Dax, Elizabeth M.; Kelleher, Anthony D.; Smith, Don E.; McPhee, Dale A.

    2010-01-01

    Several clinical studies have shown that, relative to disease progression, HIV-1 isolates that are less fit are also less pathogenic. The aim of the present study was to investigate the relationship between viral fitness and control of viral load (VL) in acute and early HIV-1 infection. Samples were obtained from subjects participating in two clinical studies. In the PULSE study, antiretroviral therapy (ART) was initiated before, or no later than six months following seroconversion. Subjects then underwent multiple structured treatment interruptions (STIs). The PHAEDRA study enrolled and monitored a cohort of individuals with documented evidence of primary infection. The subset chosen were individuals identified no later than 12 months following seroconversion to HIV-1, who were not receiving ART. The relative fitness of primary isolates obtained from study participants was investigated ex vivo. Viral DNA production was quantified using a novel real time PCR assay. Following intermittent ART, the fitness of isolates obtained from 5 of 6 PULSE subjects decreased over time. In contrast, in the absence of ART the fitness of paired isolates obtained from 7 of 9 PHAEDRA subjects increased over time. However, viral fitness did not correlate with plasma VL. Most unexpected was the high relative fitness of isolates obtained at Baseline from PULSE subjects, before initiating ART. It is widely thought that the fitness of strains present during the acute phase is low relative to strains present during chronic HIV-1 infection, due to the bottleneck imposed upon transmission. The results of this study provide evidence that the relative fitness of strains present during acute HIV-1 infection may be higher than previously thought. Furthermore, that viral fitness may represent an important clinical parameter to be considered when deciding whether to initiate ART during early HIV-1 infection. PMID:20844589

  14. Noncoding RNPs of Viral Origin

    PubMed Central

    Steitz, Joan; Borah, Sumit; Cazalla, Demian; Fok, Victor; Lytle, Robin; Mitton-Fry, Rachel; Riley, Kasandra; Samji, Tasleem

    2011-01-01

    SUMMARY Like their host cells, many viruses produce noncoding (nc)RNAs. These show diversity with respect to time of expression during viral infection, length and structure, protein-binding partners and relative abundance compared with their host-cell counterparts. Viruses, with their limited genomic capacity, presumably evolve or acquire ncRNAs only if they selectively enhance the viral life cycle or assist the virus in combating the host’s response to infection. Despite much effort, identifying the functions of viral ncRNAs has been extremely challenging. Recent technical advances and enhanced understanding of host-cell ncRNAs promise accelerated insights into the RNA warfare mounted by this fascinating class of RNPs. PMID:20719877

  15. Escaping High Viral Load Exhaustion

    PubMed Central

    Reignat, Stephanie; Webster, George J.M.; Brown, David; Ogg, Graham S.; King, Abigail; Seneviratne, Suranjith L.; Dusheiko, Geoff; Williams, Roger; Maini, Mala K.; Bertoletti, Antonio

    2002-01-01

    Deletion, anergy, and a spectrum of functional impairments can affect virus-specific CD8 cells in chronic viral infections. Here we characterize a low frequency population of CD8 cells present in chronic hepatitis B virus (HBV) infection which survive in the face of a high quantity of viral antigen. Although they do not appear to exert immunological pressure in vivo, these CD8 cells are not classically “tolerant” since they proliferate, lyse, and produce antiviral cytokines in vitro. They are characterized by altered HLA/peptide tetramer reactivity, which is not explained by TCR down-regulation or reduced functional avidity and which can be reversed with repetitive stimulation. CD8 cells with altered tetramer binding appear to have a specificity restricted to envelope antigen and not to other HBV antigens, suggesting that mechanisms of CD8 cell dysfunction are differentially regulated according to the antigenic form and presentation of individual viral antigens. PMID:11994415

  16. Plant pathogenic Pseudomonas species

    Microsoft Academic Search

    Monica Höfte; PAUL DE VOS

    In the current taxonomy, plant pathogenic Pseudomonas species are restricted to rRNA group I organisms belonging to the Gamma subclass of Proteobacteria. Currently, about 21 validly described plant pathogenic Pseudomonas species are known. The most important species is P. syringae with more than 50 described pathovars. The pathovar concept is confusing and the taxonomy of P. syringae needs revision. P.

  17. 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...

  18. Emerging foodborne pathogens

    Microsoft Academic Search

    Robert V. Tauxe

    2002-01-01

    The broad spectrum of foodborne infections has changed dramatically over time, as well-established pathogens have been controlled or eliminated, and new ones have emerged. The burden of foodborne disease remains substantial: one in four Americans is estimated to have a significant foodborne illness each year. The majority of these illnesses are not accounted for by known pathogens, so more must

  19. Nucleic Acid Transport in Plant-Pathogen Interactions

    Microsoft Academic Search

    Robert Lartey; Vitaly Citovsky

    \\u000a Transport of nucleic acid molecules is central to many plant-pathogen interactions. Nucleic acids are transported between\\u000a cells when plant viruses move their genomes from the infected into adjacent uninfected cells through plant intercellular connections,\\u000a the plasmodesmata. DNA and RNA molecules are also transported from the host cell cytoplasm into the nucleus during many viral\\u000a infections. In addition, nuclear import of

  20. Pathogen inactivation techniques.

    PubMed

    Pelletier, J P R; Transue, S; Snyder, E L

    2006-01-01

    The desire to rid the blood supply of pathogens of all types has led to the development of many technologies aimed at the same goal--eradication of the pathogen(s) without harming the blood cells or generating toxic chemical agents. This is a very ambitious goal, and one that has yet to be achieved. One approach is to shun the 'one size fits all' concept and to target pathogen-reduction agents at the Individual component types. This permits the development of technologies that might be compatible with, for example, plasma products but that would be cytocidal and thus incompatible with platelet concentrates or red blood cell units. The technologies to be discussed include solvent detergent and methylene blue treatments--designed to inactivate plasma components and derivatives; psoralens (S-59--amotosalen) designed to pathogen-reduce units of platelets; and two products aimed at red blood cells, S-303 (a Frale--frangible anchor-linker effector compound) and Inactine (a binary ethyleneimine). A final pathogen-reduction material that might actually allow one material to inactivate all three blood components--riboflavin (vitamin B2)--is also under development. The sites of action of the amotosalen (S-59), the S-303 Frale, Inactine, and riboflavin are all localized in the nucleic acid part of the pathogen. Solvent detergent materials act by dissolving the plasma envelope, thus compromising the integrity of the pathogen membrane and rendering it non-infectious. By disrupting the pathogen's ability to replicate or survive, its infectivity is removed. The degree to which bacteria and viruses are affected by a particular pathogen-reducing technology relates to its Gram-positive or Gram-negative status, to the sporulation characteristics for bacteria, and the presence of lipid or protein envelopes for viruses. Concerns related to photoproducts and other breakdown products of these technologies remain, and the toxicology of pathogen-reduction treatments is a major ongoing area of investigation. Clearly, regulatory agencies have a major role to play in the evaluation of these new technologies. This chapter will cover the several types of pathogen-reduction systems, mechanisms of action, the inactivation efficacy for specific types of pathogens, toxicology of the various systems and the published research and clinical trial data supporting their potential usefulness. Due to the nature of the field, pathogen reduction is a work in progress and this review should be considered as a snapshot in time rather than a clear picture of what the future will bring. PMID:16377551

  1. 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

  2. Emerging viral diseases of fish and shrimp

    USGS Publications Warehouse

    Winton, James R.; Walker, Peter J.

    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.

  3. Characterization of Viral Entry Inhibitors 

    E-print Network

    Chamoun Emanuelli, Ana M

    2014-08-06

    Hepatitis C virus (HCV), Human Immunodeficiency virus (HIV) and Herpes Simplex virus (HSV) are pathogenic viruses known to cause liver disorder, acquired immunodeficiency and skin lesions, respectively. Although current therapies have played...

  4. 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.

  5. Viral hepatitis in the Arctic

    Microsoft Academic Search

    Brian J McMahon

    Objectives. Summarize research on viral hepatitis in indigenous populations in the Arctic. Study De- sign. Literature review. Methods. Medline search from 1966-2003. Results. High prevalence rates of total hepatitis A antibody of > 50% and of hepatitis B of between 22% in Alaska and 42% in Greenland for total infection and between 3% in Canada and 12% in Siberia for

  6. 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

  7. Treatment of acute viral croup

    Microsoft Academic Search

    W Lenney; A D Milner

    1978-01-01

    Total respiratory resistance (RT) was measured before and after nebulised alpha-adrenergic stimulant therapy in 8 children aged 4 to 18 months who had the clinical symptoms of acute viral croup. In 7 children there was a mean fall in RT of 30% after treatment, associated with an improvement in their clinical condition. This improvement was shortlived, the resistance returning to

  8. Molecular mechanisms of viral inhibitors of RIG-I-like receptors

    PubMed Central

    Leung, Daisy W.; Basler, Christopher F.; Amarasinghe, Gaya K.

    2012-01-01

    Activation of innate immune signaling pathways through cytosolic RIG-I like receptors (RLR) is a critical response that is antagonized by many viruses. A variety of RNA related pathogen associated molecular patterns have been identified and their role in RLR activation has been examined. Recent studies suggest that several virally encoded components that antagonize RLR signaling interact with and inhibit the interferon (IFN)-?/? activation pathway using both RNA-dependent and RNA-independent mechanisms. The structural basis for these RLR inhibitory mechanisms, as well as the multifunctional nature of viral RLR antagonists, is reviewed in the context of recent biochemical and structural studies. PMID:22325030

  9. The bitter side of sweet: the role of Galectin-9 in immunopathogenesis of viral infections.

    PubMed

    Merani, Shahzma; Chen, Wenna; Elahi, Shokrollah

    2015-05-01

    In recent years, a critical role for ?-galactoside-binding protein, Galectin-9 (Gal-9) has emerged in infectious disease, autoimmunity, and cancer. It is a ligand for T cell immunoglobulin mucin domain 3 (Tim-3), a type-I glycoprotein that is persistently expressed on dysfunctional T cells during chronic viral infections. Gal-9 exerts its pivotal immunomodulatory effects by inducing apoptosis or suppressing effector functions via engagement with its receptor, Tim-3. Recent studies report elevation of circulating Gal-9 in humans infected with different viral infections. Interaction of soluble Gal-9 with Tim-3 expressed on the surface of activated CD4+ T cells renders them less susceptible to HIV-1 infection, while enhanced HIV infection occurs when Gal-9 interacts with a different receptor than Tim-3. This indicates the versatile role of Gal-9 in viral pathogenesis. For instance, higher expression of Tim-3 during chronic viral infection and elevation of plasma Gal-9 may have evolved to limit persistent immune activation and pathogenic T cells activity. In contrast, Gal-9 can suppress the effectiveness of immunity against viral infections. In agreement, Gal-9 knockout mice mount a more robust and vigorous virus-specific immune response in acute and chronic viral infections resulting in rapid viral clearance. In line with this observation, blocking Gal-9 signals to Tim-3-expressing T cells result in improved immune responses. Here we review the biological and immunological properties of Gal-9 in viral infections (HIV, HCV, HBV, HSV, CMV, influenza, and dengue virus). Manipulating Gal-9 signals may have immunotherapeutic potential and could represent an alternative approach for improving immune responses to viral infections/vaccines. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25760439

  10. DNA vaccines against viral diseases of farmed fish.

    PubMed

    Evensen, Øystein; Leong, Jo-Ann C

    2013-12-01

    Immunization by an antigen-encoding DNA was approved for commercial sale in Canada against a Novirhabdovirus infection in fish. DNA vaccines have been particularly successful against the Novirhabdoviruses while there are reports on the efficacy against viral pathogens like infectious pancreatic necrosis virus, infectious salmon anemia virus, and lymphocystis disease virus and these are inferior to what has been attained for the novirhabdoviruses. Most recently, DNA vaccination of Penaeus monodon against white spot syndrome virus was reported. Research efforts are now focused on the development of more effective vectors for DNA vaccines, improvement of vaccine efficacy against various viral diseases of fish for which there is currently no vaccines available and provision of co-expression of viral antigen and immunomodulatory compounds. Scientists are also in the process of developing new delivery methods. While a DNA vaccine has been approved for commercial use in farmed salmon in Canada, it is foreseen that it is still a long way to go before a DNA vaccine is approved for use in farmed fish in Europe. PMID:24184267

  11. ISG15 regulates peritoneal macrophages functionality against viral infection.

    PubMed

    Yángüez, Emilio; García-Culebras, Alicia; Frau, Aldo; Llompart, Catalina; Knobeloch, Klaus-Peter; Gutierrez-Erlandsson, Sylvia; García-Sastre, Adolfo; Esteban, Mariano; Nieto, Amelia; Guerra, Susana

    2013-01-01

    Upon viral infection, the production of type I interferon (IFN) and the subsequent upregulation of IFN stimulated genes (ISGs) generate an antiviral state with an important role in the activation of innate and adaptive host immune responses. The ubiquitin-like protein (UBL) ISG15 is a critical IFN-induced antiviral molecule that protects against several viral infections, but the mechanism by which ISG15 exerts its antiviral function is not completely understood. Here, we report that ISG15 plays an important role in the regulation of macrophage responses. ISG15-/- macrophages display reduced activation, phagocytic capacity and programmed cell death activation in response to vaccinia virus (VACV) infection. Moreover, peritoneal macrophages from mice lacking ISG15 are neither able to phagocyte infected cells nor to block viral infection in co-culture experiments with VACV-infected murine embryonic fibroblast (MEFs). This phenotype is independent of cytokine production and secretion, but clearly correlates with impaired activation of the protein kinase AKT in ISG15 knock-out (KO) macrophages. Altogether, these results indicate an essential role of ISG15 in the cellular immune antiviral response and point out that a better understanding of the antiviral responses triggered by ISG15 may lead to the development of therapies against important human pathogens. PMID:24137104

  12. ISG15 Regulates Peritoneal Macrophages Functionality against Viral Infection

    PubMed Central

    Llompart, Catalina; Knobeloch, Klaus-Peter; Gutierrez-Erlandsson, Sylvia; García-Sastre, Adolfo; Esteban, Mariano; Nieto, Amelia; Guerra, Susana

    2013-01-01

    Upon viral infection, the production of type I interferon (IFN) and the subsequent upregulation of IFN stimulated genes (ISGs) generate an antiviral state with an important role in the activation of innate and adaptive host immune responses. The ubiquitin-like protein (UBL) ISG15 is a critical IFN-induced antiviral molecule that protects against several viral infections, but the mechanism by which ISG15 exerts its antiviral function is not completely understood. Here, we report that ISG15 plays an important role in the regulation of macrophage responses. ISG15?/? macrophages display reduced activation, phagocytic capacity and programmed cell death activation in response to vaccinia virus (VACV) infection. Moreover, peritoneal macrophages from mice lacking ISG15 are neither able to phagocyte infected cells nor to block viral infection in co-culture experiments with VACV-infected murine embryonic fibroblast (MEFs). This phenotype is independent of cytokine production and secretion, but clearly correlates with impaired activation of the protein kinase AKT in ISG15 knock-out (KO) macrophages. Altogether, these results indicate an essential role of ISG15 in the cellular immune antiviral response and point out that a better understanding of the antiviral responses triggered by ISG15 may lead to the development of therapies against important human pathogens. PMID:24137104

  13. Shellfish-borne viral outbreaks: a systematic review.

    PubMed

    Bellou, M; Kokkinos, P; Vantarakis, A

    2013-03-01

    Investigations of disease outbreaks linked to shellfish consumption have been reported in the scientific literature; however, only few countries systematically collate and report such data through a disease surveillance system. We conducted a systematic review to investigate shellfish-borne viral outbreaks and to explore their distribution in different countries, and to determine if different types of shellfish and viruses are implicated. Six databases (Medline, Embase, Scopus, PubMed, Eurosurveillance Journal and Spingerlink electronic Journal) and a global electronic reporting system (ProMED) were searched from 1980 to July 2012. About 359 shellfish-borne viral outbreaks, alongside with nine ProMED reports, involving shellfish consumption, were identified. The majority of the reported outbreaks were located in East Asia, followed by Europe, America, Oceania, Australia and Africa. More than half of the outbreaks (63.6 %) were reported from Japan. The most common viral pathogens involved were norovirus (83.7 %) and hepatitis A virus (12.8 %). The most frequent type of consumed shellfish which was involved in outbreaks was oysters (58.4 %). Outbreaks following shellfish consumption were often attributed to water contamination by sewage and/or undercooking. Differences in reporting of outbreaks were seen between the scientific literature and ProMED. Consumption of contaminated shellfish represents a risk to public health in both developed and developing countries, but impact will be disproportionate and likely to compound existing health disparities. PMID:23412719

  14. Autistic disorder and viral infections.

    PubMed

    Libbey, Jane E; Sweeten, Thayne L; McMahon, William M; Fujinami, Robert S

    2005-02-01

    Autistic disorder (autism) is a behaviorally defined developmental disorder with a wide range of behaviors. Although the etiology of autism is unknown, data suggest that autism results from multiple etiologies with both genetic and environmental contributions, which may explain the spectrum of behaviors seen in this disorder. One proposed etiology for autism is viral infection very early in development. The mechanism, by which viral infection may lead to autism, be it through direct infection of the central nervous system (CNS), through infection elsewhere in the body acting as a trigger for disease in the CNS, through alteration of the immune response of the mother or offspring, or through a combination of these, is not yet known. Animal models in which early viral infection results in behavioral changes later in life include the influenza virus model in pregnant mice and the Borna disease virus model in newborn Lewis rats. Many studies over the years have presented evidence both for and against the association of autism with various viral infections. The best association to date has been made between congenital rubella and autism; however, members of the herpes virus family may also have a role in autism. Recently, controversy has arisen as to the involvement of measles virus and/or the measles, mumps, rubella (MMR) vaccine in the development of autism. Biological assays lend support to the association between measles virus or MMR and autism whereas epidemiologic studies show no association between MMR and autism. Further research is needed to clarify both the mechanisms whereby viral infection early in development may lead to autism and the possible involvement of the MMR vaccine in the development of autism. PMID:15804954

  15. The role of Rel/NF-kappa B proteins in viral oncogenesis and the regulation of viral transcription.

    PubMed

    Mosialos, G

    1997-04-01

    Rel/NF-kappa B is a ubiquitous transcription factor that consists of multiple polypeptide subunits, and is subject to complex regulatory mechanisms that involve protein-protein interactions, phosphorylation, ubiquitination, proteolytic degradation, and nucleocytoplasmic translocation. The sophisticated control of Rel/NF-kappa B activity is not surprising since this transcription factor is involved in a wide array of cellular responses to extracellular cues, associated with growth, development, apoptosis, and pathogen invasion. Thus, it is not unexpected that this versatile cellular homeostatic switch would be affected by a variety of viral pathogens, which have evolved mechanisms to utilize various aspects of Rel/NF-kappa B activity to facilitate their replication, cell survival and possibly evasion of immune responses. This review will cover the molecular mechanisms that are utilized by mammalian oncogenic viruses to affect the activity of Rel/NF-kappa B transcription factors and the role of Rel/NF-kappa B in the regulation of viral gene expression and replication. PMID:9299590

  16. Do viral proteins possess unique biophysical features?

    Microsoft Academic Search

    Nobuhiko Tokuriki; Christopher J. Oldfield; Vladimir N. Uversky; Igor N. Berezovsky; Dan S. Tawfik

    2008-01-01

    Natural selection shapes the sequence, structure and biophysical properties of proteins to fit their environ- ment. We hypothesize that highly thermostable proteins and viral proteins represent two opposing adaptation strategies. Thermostable proteins are highly compact and possess well-packed hydrophobic cores and inten- sely charged surfaces. By contrast, viral proteins, and RNA viral proteins in particular, display a high occur- rence

  17. Dynamics of viral hemorrhagic septicemia, viral erythrocytic necrosis and ichthyophoniasis in confined juvenile Pacific herring Clupea pallasii

    USGS Publications Warehouse

    Hershberger, P.; Hart, A.; Gregg, J.; Elder, N.; Winton, J.

    2006-01-01

    Capture of wild, juvenile herring Clupea pallasii from Puget Sound (Washington, USA) and confinement in laboratory tanks resulted in outbreaks of viral hemorrhagic septicemia (VHS), viral erythrocytic necrosis (VEN) and ichthyophoniasis; however, the timing and progression of the 3 diseases differed. The VHS epidemic occurred first, characterized by an initially low infection prevalence that increased quickly with confinement time, peaking at 93 to 98% after confinement for 6 d, then decreasing to negligible levels after 20 d. The VHS outbreak was followed by a VEN epidemic that, within 12 d of confinement, progressed from undetectable levels to 100% infection prevalence with >90% of erythrocytes demonstrating inclusions. The VEN epidemic persisted for 54 d, after which the study was terminated, and was characterized by severe blood dyscrasias including reduction of mean hematocrit from 42 to 6% and replacement of mature erythrocytes with circulating erythroblasts and ghost cells. All fish with ichthyophoniasis at capture died within the first 3 wk of confinement, probably as a result of the multiple stressors associated with capture, transport, confinement, and progression of concomitant viral diseases. The results illustrate the differences in disease ecology and possible synergistic effects of pathogens affecting marine fish and highlight the difficulty in ascribing a single causation to outbreaks of disease among populations of wild fishes. ?? Inter-Research 2006.

  18. Introduction to Pathogenic Bacteria

    Microsoft Academic Search

    Tracey Elizabeth Love; Barbara Jones

    This chapter is a brief introduction to pathogenic microorganisms and also discusses virulence factors. An understanding of\\u000a virulence factors is important, as they represent potential targets for the detection of microbial pathogens. Sources and\\u000a routes of infection are also briefly discussed with reference to specific examples. There are a number of ways in which infection\\u000a could be acquired, including via

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

    E-print Network

    Human Pathogen Importation Importing "Human" Pathogens from Outside Canada 1) Permits are not required for Risk Group 1 materals. If the material is deemed to be non- pathogenic, a courtesy notice may is required from PHAC*, please go to the PHAC website at http://www.phac- aspc.gc.ca/ols-bsl/pathogen

  20. BTI Pathogen Use Committee BTI Pathogen Use Form

    E-print Network

    Pawlowski, Wojtek

    BTI Pathogen Use Committee 4/7/04 1 BTI Pathogen Use Form Date Submitted: Date Received by PUC for space, if appropriate. 1. Are you planning to use recombinant pathogens in the BTI Plant Growth facilities? Yes No If yes, provide permit # of approved IBC r DNA MUA and attach copy. 2. List all pathogens

  1. Advances in Mimivirus Pathogenicity

    Microsoft Academic Search

    Agnès Vincent; Bernard La Scola; Laurent Papazian

    2010-01-01

    Viral diseases in the clinical setting have been extensively investigated. Viruses are now considered as potentially responsible for nosocomial infections, especially in intensive care unit (ICU) patients. Mimivirus is the largest virus known to date. Recent studies have suggested that Mimivirus could be responsible for both community-acquired and nosocomial pneumonia. These studies were mainly based on serologic diagnosis, which showed

  2. 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

  3. 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.

  4. Application of RT-PCR to study in vitro development of Cryptosporidium parvum and its viral symbiont CPV

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cryptosporidium parvum and C. hominis contain a double-stranded RNA viral symbiont termed CPV. Our research seeks to find a role for CPV in the pathogenicity and development of C. parvum. Cell cultures were infected with C. parvum sporozoites, and extracted at various times post-infection for DNA ...

  5. 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...

  6. 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...

  7. 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 ...

  8. 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...

  9. 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...

  10. 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...

  11. 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 ...

  12. Will the package contain pathogens

    E-print Network

    Will the package contain pathogens OR dry ice ? Is the material considered hazardous by the DOT? Do ? NO NO YES YES Pack and ship. If you have identified any hazardous pathogenic substances, ensure you take EHS to a location outside of the US, and: - The materials are pathogens listed on Stanford's Dual Use Pathogen List

  13. A comprehensive Prunus pathogen array

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A comprehensive pathogen array was developed for the detection of pathogens of many major crops in the Prunus genus. The APS disease lists for peach, plum, apricot and cherry were combined into a single Prunus pathogen list, containing 102 pathogens (75 fungi, 18 viruses, 6 bacteria and 3 phytoplasm...

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

    PubMed

    Shekhar, M S; Ponniah, A G

    2015-07-01

    Viral disease outbreaks are a major concern impeding the development of the shrimp aquaculture industry. The viral disease due to white spot syndrome virus (WSSV) observed in early 1990s still continues unabated affecting the shrimp farms and cause huge economic loss to the shrimp aquaculture industry. In the absence of effective therapeutics to control WSSV, it is important to understand viral pathogenesis and shrimp response to WSSV at the molecular level. Identification and molecular characterization of WSSV proteins and receptors may facilitate in designing and development of novel therapeutics and antiviral drugs that may inhibit viral replication. Investigations into host-pathogen interactions might give new insights to viral infectivity, tissue tropism and defence mechanism elicited in response to WSSV infection. However, due to the limited information on WSSV gene function and host immune response, the signalling pathways which are associated in shrimp pathogen interaction have also not been elucidated completely. In the present review, the focus is on those shrimp proteins and receptors that are potentially involved in virus infection or in the defence mechanism against WSSV. In addition, the major signalling pathways involved in the innate immune response and the role of apoptosis in host-pathogen interaction is discussed. PMID:24953507

  15. A viral RNA structural element alters host recognition of non-self RNA

    PubMed Central

    Hyde, Jennifer L.; Gardner, Christina L.; Kimura, Taishi; White, James P.; Liu, Gai; Trobaugh, Derek W.; Huang, Cheng; Tonelli, Marco; Paessler, Slobodan; Takeda, Kiyoshi; Klimstra, William B.; Amarasinghe, Gaya K.; Diamond, Michael S.

    2014-01-01

    Although interferon (IFN) signaling induces genes that limit viral infection, many pathogenic viruses overcome this host response. As an example, 2?-O methylation of the 5? cap of viral RNA subverts mammalian antiviral responses by evading restriction of Ifit1, an IFN-stimulated gene that regulates protein synthesis. However, alphaviruses replicate efficiently in cells expressing Ifit1 even though their genomic RNA has a 5? cap lacking 2?-O methylation. We show that pathogenic alphaviruses use secondary structural motifs within the 5?-untranslated region (UTR) of their RNA to alter Ifit1 binding and function. Mutations within the 5?-UTR affecting RNA structural elements enabled restriction by or antagonism of Ifit1 in vitro and in vivo. These results identify an evasion mechanism by which viruses use RNA structural motifs to avoid immune restriction. PMID:24482115

  16. Two Asian highly pathogenic strains of Type 2 PRRSV in United States swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic PRRSV (HP-PRRSV) has been circulating in Asia for 7 years. rJXwn06 and rSRV07 were rescued from infectious clones of two HP-PRRSV for investigation at the National Animal Disease Center. The clinical disease and viral replication kinetics of HP-PRRSV were compared to prototype stra...

  17. REMOVAL AND FATE OF SPECIFIC MICROBIAL PATHOGENS WITHIN ON-SITE WASTEWATER TREATMENT SYSTEMS

    E-print Network

    Pillai, Suresh D.; Lesikar, Bruce A.

    ...................................................................................................................11 Submerged flow constructed wetland........................................................................12 Aerobic treatment unit ...............................................................................................12 Chapter 4... wetland and an aerobic treatment unit to remove bacterial and viral pathogens from wastewater streams was evaluated in this study. Salmonella sp. and a bacteriophages tracer were used in conjunction with the conservative bromide tracer to understand...

  18. RESEARCH Open Access Host-pathogen interactome mapping for HTLV-1

    E-print Network

    Paris-Sud XI, Université de

    for the systematic mapping and comparison of pathogen-host protein interactions that includes stringent yeast two and presents new insights on biological pathways involved in retroviral infection. Keywords: HTLV, Interactome and proliferation path- ways [6]. Modulations of viral and cellular function upon infection rely on crosstalk

  19. 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 ...

  20. Tickling the TLR7 to cure viral hepatitis.

    PubMed

    Funk, Emily; Kottilil, Shyam; Gilliam, Bruce; Talwani, Rohit

    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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Association of HLA-alleles with the immune regulation of chronic viral infections.

    PubMed

    Elahi, Shokrollah; Horton, Helen

    2012-08-01

    Cytotoxic CD8 T lymphocytes (CTLs) have an astonishing ability to eliminate pathogen-infected cells. However, if uncontrolled, these CTLs could cause devastating pathology to host tissues. CD8(+) effector T cells, therefore, interact with antigen-presenting cells and other immune cells, such as regulatory T cells (Tregs), to regulate further on-site expansion and differentiation of the effector cells. This ensures protection of the host with minimal bystander pathological consequences. During prolonged chronic infections CTLs, however, often lose effector function. Induction of multiple inhibitory pathways is emerging as a major regulator converting effector CTLs into exhausted CTLs during chronic viral infections such as HIV, HCV and HBV. The mechanisms involved in induction of exhaustion during chronic viral infections are the focus of this article. Blockade of inhibitory pathways could potentially restore functional capabilities to exhausted CTLs and represents a potential immune-based intervention in chronic viral infections. PMID:22595281

  7. A role for IRF3-dependent RXR? repression in hepatotoxicity associated with viral infections

    PubMed Central

    Chow, Edward K.; Castrillo, Antonio; Shahangian, Arash; Pei, Liming; O'Connell, Ryan M.; Modlin, Robert L.; Tontonoz, Peter; Cheng, Genhong

    2006-01-01

    Viral infections and antiviral responses have been linked to several metabolic diseases, including Reye's syndrome, which is aspirin-induced hepatotoxicity in the context of a viral infection. We identify an interferon regulatory factor 3 (IRF3)–dependent but type I interferon–independent pathway that strongly inhibits the expression of retinoid X receptor ? (RXR?) and suppresses the induction of its downstream target genes, including those involved in hepatic detoxification. Activation of IRF3 by viral infection in vivo greatly enhances bile acid– and aspirin-induced hepatotoxicity. Our results provide a critical link between the innate immune response and host metabolism, identifying IRF3-mediated down-regulation of RXR? as a molecular mechanism for pathogen-associated metabolic diseases. PMID:17074929

  8. 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

  9. Complete genome sequence of viral hemorrhagic septicemia virus isolated from an olive flounder in South Korea.

    PubMed

    Kim, Jong-Oh; Kim, Wi-Sik; Nishizawa, Toyohiko; Oh, Myung-Joo

    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. 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

  11. 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

  12. Bovine viral diarrhoea virus: its effects on ovarian function in the cow

    Microsoft Academic Search

    M. D Fray; G. E Mann; M. C Clarke; B Charleston

    2000-01-01

    Bovine viral diarrhoea virus (BVDV) is a major cattle pathogen responsible for a spectrum of symptoms, including reproductive failure. In this paper we investigate how BVDV interacts with the ovary. The viruses’ tropism for the pre-ovulatory oocyte was studied by indirect immunohistochemistry. Two monoclonal antibodies, raised against the non-structural protein NS3 and the envelope glycoprotein E2 were used to probe

  13. Viral Control of Mitochondrial Apoptosis

    Microsoft Academic Search

    Lorenzo Galluzzi; Catherine Brenner; Eugenia Morselli; Zahia Touat; Guido Kroemer

    2008-01-01

    Throughout the process of pathogen–host co-evolution, viruses have developed a battery of distinct strategies to overcome biochemical and immunological defenses of the host. Thus, viruses have acquired the capacity to subvert host cell apoptosis, control inflammatory responses, and evade immune reactions. Since the elimination of infected cells via programmed cell death is one of the most ancestral defense mechanisms against

  14. Viral enteric infections of poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Enteric diseases cause great economic losses to the poultry industry mostly from depressed weight gains, impaired feed efficiency, and decreased flock uniformity. Enteric syndromes have been described in both young turkeys and chickens and likely result from infection by a mixture of pathogenic age...

  15. 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

  16. Toll-like receptor 3 in viral pathogenesis: friend or foe?

    PubMed

    Perales-Linares, Renzo; Navas-Martin, Sonia

    2013-10-01

    Viral infections frequently induce acute and chronic inflammatory diseases, yet the contribution of the innate immune response to a detrimental host response remains poorly understood. In virus-infected cells, double-stranded RNA (dsRNA) is generated as an intermediate during viral replication. Cell necrosis (and the release of endogenous dsRNA) is a common event during both sterile and infectious inflammatory processes. The discovery of Toll-like receptor 3 (TLR3) as an interferon-inducing dsRNA sensor led to the assumption that TLR3 was the master sentinel against viral infections. This simplistic view has been challenged by the discovery of at least three members of the DExd/H-box helicase cytosolic sensors of dsRNA that share with TLR3 the Toll-interleukin-1 receptor (TIR) -adapter molecule TIR domain-containing adaptor protein interferon-? (TRIF) for downstream type I interferon signalling. Data are conflicting on the role of TLR3 in protective immunity against viruses in the mouse model. Varying susceptibility to infection and disease outcomes have been reported in TLR3-immunodeficient mice. Surprisingly, the susceptibility to develop herpes simplex virus-1 encephalitis in humans with inborn defects of the TLR3 pathway varies, and TLR3-deficient humans do not show increased susceptibility to other viral infections. Therefore, a current challenge is to understand the protective versus pathogenic contribution of TLR3 in viral infections. We review recent advances in the identification of TLR3-signalling pathways, endogenous and virus-induced negative regulators of the TLR3 cascade, and discuss the protective versus pathogenic role of TLR3 in viral pathogenesis. PMID:23909285

  17. Viral proteases as targets for drug design.

    PubMed

    Skore?ski, Marcin; Sie?czyk, Marcin

    2013-01-01

    In order to productively infect a host, viruses must enter the cell and force host cell replication mechanisms to produce new infectious virus particles. The success of this process unfortunately results in disease progression and, in the case of infection with many viral species, may cause mortality. The discoveries of Louis Pasteur and Edward Jenner led to one of the greatest advances in modern medicine - the development of vaccines that generate long-lasting memory immune responses to combat viral infection. Widespread use of vaccines has reduced mortality and morbidity associated with viral infection and, in some cases, has completely eradicated virus from the human population. Unfortunately, several viral species maintain a significant ability to mutate and "escape" vaccine-induced immune responses. Thus, novel anti-viral agents are required for treatment and prevention of viral disease. Targeting proteases that are crucial in the viral life cycle has proven to be an effective method to control viral infection, and this avenue of investigation continues to generate anti-viral treatments. Herein, we provide the reader with a brief history as well as a comprehensive review of the most recent advances in the design and synthesis of viral protease inhibitors. PMID:23016690

  18. The Keystone Pathogen Hypothesis

    PubMed Central

    Hajishengallis, George; Darveau, Richard P.; Curtis, Michael A.

    2012-01-01

    Recent studies have highlighted the importance of the human microbiome in host health and disease. However, for the most part the mechanisms by which the microbiome mediates disease, or protection from it, remain poorly understood. The “keystone pathogen” hypothesis holds that certain low-abundance microbial pathogens can orchestrate inflammatory disease by remodelling a normally benign microbiota into a dysbiotic one. In this Opinion, we critically assess the available literature in support of this hypothesis, which may provide a novel conceptual basis for the development of targeted diagnostic and treatment modalities for complex dysbiotic diseases. PMID:22941505

  19. Bloodborne Pathogens Program

    NASA Technical Reports Server (NTRS)

    Blasdell, Sharon

    1993-01-01

    The final rule on the Occupational Exposure to Bloodborne Pathogens was published in the Federal Register on Dec. 6, 1991. This Standard, 29 CFR Part 1910.130, is expected to prevent 8,900 hepatitis B infections and nearly 200 deaths a year in healthcare workers in the U.S. The Occupational Medicine and Environmental Health Services at KSC has been planning to implement this standard for several years. Various aspects of this standard and its Bloodborne Pathogens Program at KSC are discussed.

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

    PubMed Central

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

    2015-01-01

    Highly pathogenic avian influenza virus (HPAIV) H5N1 has been endemic in Egypt since 2006, and there is increasing concern for its potential to become highly transmissible among humans. Infection by HPAIV H5N1 has been described in experimentally challenged birds. However, the pathogenicity of the H5N1 isolated in Egypt has never been reported in naturally infected chickens and ducks. Here we report a 2013 outbreak of HPAIV H5N1 in commercial poultry farms and backyards in Sharkia Province, Egypt. The main symptoms were ecchymosis on the shanks and feet, cyanosis of the comb and wattles, subcutaneous edema of the head and neck for chickens, and nervous signs (torticollis) for ducks. Within 48-72 hrs of the onset of illness, the average mortality rates were 22.8-30% and 28.5-40% in vaccinated chickens and non-vaccinated ducks, respectively. Tissue samples of chickens and ducks were collected for analyses with cross-section immunohistochemistry and real-time RT-PCR for specific viral RNA transcripts. While viral RNA was detected in nearly all tissues and sera collected, viral nucleoprotein was detected almost ubiquitously in all tissues, including testis. Interestingly, viral antigen was also observed in endothelial cells of most organs in chickens, and clearly detected in the trachea and brain in particular. Viral nucleoprotein was also detected in mononuclear cells of various organs, especially pulmonary tissue. We performed phylogenetic analyses and compared the genomic sequences of the hemagglutinin (HA) and nonstructural proteins (NS) among the isolated viruses, the HPAIV circulated in Egypt in the past and currently, and some available vaccine strains. Further analysis of deduced amino acids of both HA and NS1 revealed that our isolates carried molecular determinants of HPAIV, including the multibasic amino acids (PQGERRRK/KR*GLF) in the cleavage site in HA and glutamate at position 92 (D92E) in NS1. This is the first report of the pathogenicity of the HPAIVH5N1 strain currently circulating in naturally infected poultry in Egypt, which may provide unique insights into the viral pathogenesis in HPAIV-infected chickens and ducks. PMID:25962145

  1. Blowback: new formal perspectives on agriculturally driven pathogen evolution and spread.

    PubMed

    Wallace, R; Wallace, R G

    2015-07-01

    By their diversity in time, space, and mode, traditional and conservation agricultures can create barriers limiting pathogen evolution and spread analogous to a sterilizing temperature. Large-scale monocropping and confined animal feeding-lot operations remove such barriers, resulting, above agroecologically specific thresholds, in the development and wide propagation of novel disease strains. We apply a newly developed class of necessary-conditions statistical models of evolutionary process, first using the theory on an evolutionarily stable viral pathogen vulnerable to vaccine treatment: post-World War II poliomyelitis emerged in the UK and USA from sudden widespread adoption of automobile ownership and usage. We then examine an evolutionarily variable pathogen, swine influenza in North America. The model suggests epidemiological blowback from globalizing intensive husbandry and the raising and shipping of monoculture livestock across increasing expanses, is likely to be far more consequential, driving viral selection for greater virulence and lowered response to biomedical intervention. PMID:26050716

  2. Potential use of microarray technology for rapid identification of central nervous system pathogens.

    PubMed

    Hanson, Eric H; Niemeyer, Debra M; Folio, Les; Agan, Brian K; Rowley, Robb K

    2004-08-01

    Outbreaks of central nervous system (CNS) diseases result in significant productivity and financial losses, threatening peace and wartime readiness capabilities. To meet this threat, rapid clinical diagnostic tools for detecting and identifying CNS pathogens are needed. Current tools and techniques cannot efficiently deal with CNS pathogen diversity; they cannot provide real-time identification of pathogen serogroups and strains, and they require days, sometimes weeks, for examination of tissue culture. Rapid and precise CNS pathogen diagnostics are needed to provide the opportunity for tailored therapeutic regimens and focused preventive efforts to decrease morbidity and mortality. Such diagnostics are available through genetic and genomic technologies, which have the potential for reducing the time required in serogroup or strain identification from 500+ hours for some viral cultures to less than 3 hours for all pathogens. In the near future, microarray diagnostics and future derivations of these technologies will change the paradigm used for outbreak investigations and will improve health care for all. PMID:15379069

  3. 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

  4. 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...

  5. 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...

  6. Actinomycetes as plant pathogens

    Microsoft Academic Search

    Romano Locci

    1994-01-01

    Biology, taxonomy, pathogenicity and control of plant disease inducing actinomycetes are reviewed. Recent progress in the study of potato, sweet potato, blueberry and fruit and forest tree diseases is illustrated. The role in potato scab pathogenesis of the newly discovered phytotoxins, thaxtomins, is discussed.

  7. Opportunistic Pathogenic Yeasts

    NASA Astrophysics Data System (ADS)

    Banerjee, Uma

    Advances in medical research, made during the last few decades, have improved the prophylactic, diagnostic and therapeutic capabilities for variety of infections/diseases. However, many of the prophylactic and therapeutic procedures have been seen in many instances to exact a price of host-vulnerability to an expanding group of opportunistic pathogens and yeasts are one of the important members in it. Fortunately amongst the vast majority of yeasts present in nature only few are considered to have the capability to cause infections when certain opportunities predisposes and these are termed as ‘opportunistic pathogenic yeasts.’ However, the term ‘pathogenic’ is quite tricky, as it depends of various factors of the host, the ‘bug’ and the environment to manifest the clinical infection. The borderline is expanding. In the present century with unprecedented increase in number of immune-compromised host in various disciplines of health care settings, where any yeast, which has the capability to grow at 37 ° C (normal body temperature of human), can be pathogenic and cause infection in particular situation

  8. 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

  9. Update of pathogen reduction technology for therapeutic plasma.

    PubMed

    Chakrabarty, P; Rudra, S; Hoque, M M

    2010-04-01

    In the developed world, blood products are tested for the presence of some of pathogens prior to administration. There exists a small, but definite risk of transmission of infectious agents. The risk of transmission of viral infection is due to the "window period": the period of time between the infection of a donor and the development of detectable level of antibodies. Nucleic acid amplification testing (NAT) was introduced for HIV and HCV in the United States in 1998 and has shortened the window period and further decreased the incidence of pathogens in transfused units of blood products. The development of increasingly sensitive laboratory screening methods and restrictive donor criteria has greatly decreased the risk of transmission of many pathogens through blood transfusion; however, transfusion is still not risk free. Blood is currently not tested for many potentially dangerous known pathogens. The emergence of new agents such as West Nile Virus (WNV) demonstrates that potential threats to the blood supply continue to emerge world wide. The testing and donor rejection methods currently used to screen the blood supply may not offer complete protection against all of these emerging infectious agents. This overview aims to provide an update on the continual improvements in blood component safety in particular using methods that target pathogen's nucleic acid. PMID:20395932

  10. 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.

  11. DNA methyltransferase DNMT3A associates with viral proteins and impacts HSV-1 infection.

    PubMed

    Rowles, Daniell L; Tsai, Yuan-Chin; Greco, Todd M; Lin, Aaron E; Li, Minghao; Yeh, Justin; Cristea, Ileana M

    2015-06-01

    Viral infections can alter the cellular epigenetic landscape, through modulation of either DNA methylation profiles or chromatin remodeling enzymes and histone modifications. These changes can act to promote viral replication or host defense. Herpes simplex virus type 1 (HSV-1) is a prominent human pathogen, which relies on interactions with host factors for efficient replication and spread. Nevertheless, the knowledge regarding its modulation of epigenetic factors remains limited. Here, we used fluorescently-labeled viruses in conjunction with immunoaffinity purification and MS to study virus-virus and virus-host protein interactions during HSV-1 infection in primary human fibroblasts. We identified interactions among viral capsid and tegument proteins, detecting phosphorylation of the capsid protein VP26 at sites within its UL37-binding domain, and an acetylation within the major capsid protein VP5. Interestingly, we found a nuclear association between viral capsid proteins and the de novo DNA methyltransferase DNA (cytosine-5)-methyltransferase 3A (DNMT3A), which we confirmed by reciprocal isolations and microscopy. We show that drug-induced inhibition of DNA methyltransferase activity, as well as siRNA- and shRNA-mediated DNMT3A knockdowns trigger reductions in virus titers. Altogether, our results highlight a functional association of viral proteins with the mammalian DNA methyltransferase machinery, pointing to DNMT3A as a host factor required for effective HSV-1 infection. PMID:25758154

  12. 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).

  13. WATERBORNE PATHOGENS IN URBAN WATERSHEDS

    EPA Science Inventory

    Pathogens are microorganisms that can cause sickness or even death. A serious concern for managers of water resources, pathogens in the urban environment easily enter waters through a number of pathways, including discharge of inadequately treated sewage, stormwater runoff, combi...

  14. Viral diversity and clonal evolution from unphased genomic data

    PubMed Central

    2014-01-01

    Background Clonal expansion is a process in which a single organism reproduces asexually, giving rise to a diversifying population. It is pervasive in nature, from within-host pathogen evolution to emergent infectious disease outbreaks. Standard phylogenetic tools rely on full-length genomes of individual pathogens or population consensus sequences (phased genotypes). Although high-throughput sequencing technologies are able to sample population diversity, the short sequence reads inherent to them preclude assessing whether two reads originate from the same clone (unphased genotypes). This obstacle severely limits the application of phylogenetic methods and investigation of within-host dynamics of acute infections using this rich data source. Methods We introduce two measures of diversity to study the evolution of clonal populations using unphased genomic data, which eliminate the need to construct full-length genomes. Our method follows a maximum likelihood approach to estimate evolutionary rates and times to the most recent common ancestor, based on a relaxed molecular clock model; independent of a growth model. Deviations from neutral evolution indicate the presence of selection and bottleneck events. Results We evaluated our methods in silico and then compared it against existing approaches with the well-characterized 2009 H1N1 influenza pandemic. We then applied our method to high-throughput genomic data from marburgvirus-infected non-human primates and inferred the time of infection and the intra-host evolutionary rate, and identified purifying selection in viral populations. Conclusions Our method has the power to make use of minor variants present in less than 1% of the population and capture genomic diversification within days of infection, making it an ideal tool for the study of acute RNA viral infection dynamics. PMID:25573168

  15. Curing a viral infection by targeting the host: the example of cyclophilin inhibitors.

    PubMed

    Lin, Kai; Gallay, Philippe

    2013-07-01

    Every step of the viral life cycle is dependent on the host, which potentially can be explored for antiviral targets. Historically, however, drug discovery has focused mainly on viral targets, because of their perceived specificity. Efforts to pursue host targets have been largely hampered by concern over potential on-target toxicity, the lack of predictive cell culture and animal models, and the complexity of host-virus interactions. On the other hand, there are distinct advantages of targeting the host, such as creating a high barrier to resistance, providing broad coverage of different genotypes/serotypes and possibly even multiple viruses, and expanding the list of potential targets, when druggable viral targets are limited. Taking hepatitis C virus (HCV) as the example, there are more than 20 inhibitors of the viral protease, polymerase and NS5A protein currently in advanced clinical testing. However, resistance has become a main challenge with these direct-acting antivirals, because HCV, an RNA virus, is notoriously prone to mutation, and a single mutation in the viral target may prevent the binding of an inhibitor, and rendering it ineffective. Host cyclophilin inhibitors have shown promising effects both in vitro and in patients to prevent the emergence of resistance and to cure HCV infection, either alone or in combination with other agents. They are also capable of blocking the replication of a number of other viral pathogens. While the road to developing host-targeting antivirals has been less traveled, and significant challenges remain, delivering the most effective antiviral regimen, which may comprise inhibitors of both host and viral targets, should be well worth the effort. PMID:23578729

  16. 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.

  17. 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.

  18. Viral piracy: HIV-1 targets dendritic cells for transmission.

    PubMed

    Lekkerkerker, Annemarie N; van Kooyk, Yvette; Geijtenbeek, Teunis B H

    2006-04-01

    Dendritic cells (DCs), the professional antigen presenting cells, are critical for host immunity by inducing specific immune responses against a broad variety of pathogens. Remarkably the human immunodeficiency virus-1 (HIV-1) subverts DC function leading to spread of the virus. At an early phase of HIV-1 transmission, DCs capture HIV-1 at mucosal surfaces and transmit the virus to T cells in secondary lymphoid tissues. Capture of the virus on DCs takes place via C-type lectins of which the dendritic cell-specific intercellular adhesion molecule-3 (ICAM-3) grabbing nonintegrin (DC-SIGN) is the best studied. DC-SIGN-captured HIV-1 particles accumulate in CD81(+) multivesicular bodies (MVBs) in DCs and are subsequently transmitted to CD4+ T cells resulting in infection of T cells. The viral cell-to-cell transmission takes place at the DC-T cell interface termed the infectious synapse. Recent studies demonstrate that direct infection of DCs contributes to the transmission to T cells at a later phase. Moreover, the infected DCs may function as cellular reservoirs for HIV-1. This review discusses the different processes that govern viral piracy of DCs by HIV-1, emphasizing the intracellular routing of the virus from capture on the cell surface to egress in the infectious synapse. PMID:16611055

  19. Dietary selenium in adjuvant therapy of viral and bacterial infections.

    PubMed

    Steinbrenner, Holger; Al-Quraishy, Saleh; Dkhil, Mohamed A; Wunderlich, Frank; Sies, Helmut

    2015-01-01

    Viral and bacterial infections are often associated with deficiencies in macronutrients and micronutrients, including the essential trace element selenium. In selenium deficiency, benign strains of Coxsackie and influenza viruses can mutate to highly pathogenic strains. Dietary supplementation to provide adequate or supranutritional selenium supply has been proposed to confer health benefits for patients suffering from some viral diseases, most notably with respect to HIV and influenza A virus (IAV) infections. In addition, selenium-containing multimicronutrient supplements improved several clinical and lifestyle variables in patients coinfected with HIV and Mycobacterium tuberculosis. Selenium status may affect the function of cells of both adaptive and innate immunity. Supranutritional selenium promotes proliferation and favors differentiation of naive CD4-positive T lymphocytes toward T helper 1 cells, thus supporting the acute cellular immune response, whereas excessive activation of the immune system and ensuing host tissue damage are counteracted through directing macrophages toward the M2 phenotype. This review provides an up-to-date overview on selenium in infectious diseases caused by viruses (e.g., HIV, IAV, hepatitis C virus, poliovirus, West Nile virus) and bacteria (e.g., M. tuberculosis, Helicobacter pylori). Data from epidemiologic studies and intervention trials, with selenium alone or in combination with other micronutrients, and animal experiments are discussed against the background of dietary selenium requirements to alter immune functions. PMID:25593145

  20. Bovine viral diarrhea virus infection induces autophagy in MDBK cells.

    PubMed

    Fu, Qiang; Shi, Huijun; Ren, Yan; Guo, Fei; Ni, Wei; Qiao, Jun; Wang, Pengyan; Zhang, Hui; Chen, Chuangfu

    2014-07-01

    Bovine viral diarrhea virus (BVDV) is an enveloped, positive-sense, single-stranded RNA virus that belongs to the genus Pestivirus (Flaviviridae). The signaling pathways and levels of signaling molecules are altered in Madin-Darby Bovine Kidney (MDBK) cells infected with BVDV. Autophagy is a conservative biological degradation pathway that mainly eliminates and degrades damaged or superfluous organelles and macromolecular complexes for intracellular recycling in eukaryotic cells. Autophagy can also be induced as an effective response to maintain cellular homeostasis in response to different stresses, such as nutrient or growth factor deprivation, hypoxia, reactive oxygen species exposure and pathogen infection. However, the effects of BVDV infection on autophagy in MDBK cells remain unclear. Therefore, we performed an analysis of autophagic activity after BVDV NADL infection using real-time PCR, electron microscopy, laser confocal microscopy, and Western blotting analysis. The results demonstrated that BVDV NADL infection increased autophagic activity and significantly elevated the expression levels of the autophagy-related genes Beclin1 and ATG14 in MDBK cells. However, the knockdown of Beclin1 and ATG14 by RNA interference (RNAi) did not affect BVDV NADL infection-related autophagic activity. These findings provided a novel perspective to elaborate the effects of viral infection on the host cells. PMID:24972811

  1. 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

  2. Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation

    PubMed Central

    Anishchenko, Michael; Bowen, Richard A.; Paessler, Slobodan; Austgen, Laura; Greene, Ivorlyne P.; Weaver, Scott C.

    2006-01-01

    RNA viruses are notorious for their genetic plasticity and propensity to exploit new host-range opportunities, which can lead to the emergence of human disease epidemics such as severe acute respiratory syndrome, AIDS, dengue, and influenza. However, the mechanisms of host-range change involved in most of these viral emergences, particularly the genetic mechanisms of adaptation to new hosts, remain poorly understood. We studied the emergence of Venezuelan equine encephalitis virus (VEEV), an alphavirus pathogen of people and equines that has had severe health and economic effects in the Americas since the early 20th century. Between epidemics, VEE disappears for periods up to decades, and the viral source of outbreaks has remained enigmatic. Combined with phylogenetic analyses to predict mutations associated with a 1992–1993 epidemic, we used reverse genetic studies to identify an envelope glycoprotein gene mutation that mediated emergence. This mutation allowed an enzootic, equine-avirulent VEEV strain, which circulates among rodents in nearby forests to adapt for equine amplification. RNA viruses including alphaviruses exhibit high mutation frequencies. Therefore, ecological and epidemiological factors probably constrain the frequency of VEE epidemics more than the generation, via mutation, of amplification-competent (high equine viremia) virus strains. These results underscore the ability of RNA viruses to alter their host range, virulence, and epidemic potential via minor genetic changes. VEE also demonstrates the unpredictable risks to human health of anthropogenic changes such as the introduction of equines and humans into habitats that harbor zoonotic RNA viruses. PMID:16549790

  3. Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation.

    PubMed

    Anishchenko, Michael; Bowen, Richard A; Paessler, Slobodan; Austgen, Laura; Greene, Ivorlyne P; Weaver, Scott C

    2006-03-28

    RNA viruses are notorious for their genetic plasticity and propensity to exploit new host-range opportunities, which can lead to the emergence of human disease epidemics such as severe acute respiratory syndrome, AIDS, dengue, and influenza. However, the mechanisms of host-range change involved in most of these viral emergences, particularly the genetic mechanisms of adaptation to new hosts, remain poorly understood. We studied the emergence of Venezuelan equine encephalitis virus (VEEV), an alphavirus pathogen of people and equines that has had severe health and economic effects in the Americas since the early 20th century. Between epidemics, VEE disappears for periods up to decades, and the viral source of outbreaks has remained enigmatic. Combined with phylogenetic analyses to predict mutations associated with a 1992-1993 epidemic, we used reverse genetic studies to identify an envelope glycoprotein gene mutation that mediated emergence. This mutation allowed an enzootic, equine-avirulent VEEV strain, which circulates among rodents in nearby forests to adapt for equine amplification. RNA viruses including alphaviruses exhibit high mutation frequencies. Therefore, ecological and epidemiological factors probably constrain the frequency of VEE epidemics more than the generation, via mutation, of amplification-competent (high equine viremia) virus strains. These results underscore the ability of RNA viruses to alter their host range, virulence, and epidemic potential via minor genetic changes. VEE also demonstrates the unpredictable risks to human health of anthropogenic changes such as the introduction of equines and humans into habitats that harbor zoonotic RNA viruses. PMID:16549790

  4. 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. PMID:25883930

  5. Windward Community College BLOODBORNE PATHOGENS

    E-print Network

    Olsen, Stephen L.

    Windward Community College BLOODBORNE PATHOGENS EXPOSURE CONTROL PLAN FOR NON-RESEARCH PERSONNEL with this mission, Windward Community College has established a Bloodborne Pathogens program which includes) Bloodborne Pathogens Standard. 2.2 Scope This ECP applies to all Windward Community College non

  6. Traits of Pathogens Negatively Affecting

    E-print Network

    Schweik, Charles M.

    Traits of Pathogens Negatively Affecting Livestock Lindsey Youngman, Kelly Moffett, Ryan Crawford, Taylor Arsenault #12;Hypothesis Pathogens that can be transmitted via multiple pathways are most likely to have a significant negative consequence on livestock. On the contrary, pathogens that are transmitted

  7. 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

  8. Illuminating viral infections in the nervous system

    Microsoft Academic Search

    Silvia S. Kang; Dorian B. McGavern

    2011-01-01

    Viral infections are a major cause of human disease. Although most viruses replicate in peripheral tissues, some have developed unique strategies to move into the nervous system, where they establish acute or persistent infections. Viral infections in the central nervous system (CNS) can alter homeostasis, induce neurological dysfunction and result in serious, potentially life-threatening inflammatory diseases. This Review focuses on

  9. Molecular Engineering of Viral Gene Delivery Vehicles

    E-print Network

    Schaffer, David V.

    The Annual Review of Biomedical Engineering is online at bioeng.annualreviews.org This article's doi: 10 with novel gene delivery capabilities. Rational design of viral vectors has yielded successful advances-based design promise to aid the translation of engineered viral vectors toward the clinic. 169 Annu

  10. 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

  11. 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

  12. Itchy fish and viral dermatopathies: sampling, diagnosis, and management of common viral diseases.

    PubMed

    Weber, E P Scott

    2013-09-01

    Viral dermatopathies of fish bear clinical signs similar to those of dermatopathies from other causes. This article offers an overview to approaching dermatologic presentations in fish, with an emphasis on sampling, diagnosis, and management of viral dermatopathies, building on previous publications. It is vital to recognize clinical signs associated with viral dermatopathies because there are currently no treatments available. Avoidance and prevention is the key to controlling viral diseases in fish. Optimizing husbandry practices and providing appropriate quarantine procedures can help prevent viral disease outbreaks in collection and aquaculture stocks. PMID:24018032

  13. Viral Etiology and Clinical Profiles of Children with Severe Acute Respiratory Infections in China

    PubMed Central

    Lu, Roujian; He, Bin; Liu, Chunyan; Ma, Xuejun; Tan, Wenjie

    2013-01-01

    Background No comprehensive analysis is available on the viral etiology and clinical characterization among children with severe acute respiratory infection (SARI) in China during 2009 H1N1 pandemic and post-pandemic period. Methods Cohort of 370 hospitalized children (1 to 72 months) with SARI from May 2008 to March 2010 was enrolled in this study. Nasopharyngeal aspirate (NPA) specimens were tested by a commercial assay for 18 respiratory viral targets. The viral distribution and its association with clinical character were statistically analyzed. Results Viral pathogen was detected in 350 (94.29%) of children with SARI. Overall, the most popular viruses were: enterovirus/rhinovirus (EV/RV) (54.05%), respiratory syncytial virus (RSV) (51.08%), human bocavirus (BoCA) (33.78%), human parainfluenzaviruse type 3 (PIV3) (15.41%), and adenovirus (ADV) (12.97%). Pandemic H1N1 was the dominant influenza virus (IFV) but was only detected in 20 (5.41%) of children. Moreover, detection rate of RSV and human metapneumovirus (hMPV) among suburb participants were significantly higher than that of urban area (P<0.05). Incidence of VSARI among suburb participants was also significant higher, especially among those of 24 to 59 months group (P<0.05). Conclusion Piconaviruses (EV/RV) and paramyxoviruses are the most popular viral pathogens among children with SARI in this study. RSV and hMPV significantly increase the risk of SARI, especially in children younger than 24 months. Higher incidence of VSARI and more susceptibilities to RSV and hMPV infections were found in suburban patients. PMID:23991128

  14. 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

  15. 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

  16. 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

  17. A novel host-proteome signature for distinguishing between acute bacterial and viral infections.

    PubMed

    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

  18. Viral infections of the folds (intertriginous areas).

    PubMed

    Ad??en, Esra; Önder, Meltem

    2015-01-01

    Viruses are considered intracellular obligates with a nucleic acid, either RNA or DNA. They have the ability to encode proteins involved in viral replication and production of the protective coat within the host cells but require host cell ribosomes and mitochondria for translation. The members of the families Herpesviridae, Poxviridae, Papovaviridae, and Picornaviridae are the most commonly known agents for the cutaneous viral diseases, but other virus families, such as Adenoviridae, Togaviridae, Parvoviridae, Paramyxoviridae, Flaviviridae, and Hepadnaviridae, can also infect the skin. Though the cutaneous manifestations of viral infections are closely related to the type and the transmission route of the virus, viral skin diseases may occur in almost any part of the body. In addition to friction caused by skin-to-skin touch, skin folds are warm and moist areas of the skin that have limited air circulation. These features provide a fertile breeding ground for many kinds of microorganisms, including bacteria and fungi. In contrast to specific bacterial and fungal agents that have an affinity for the skin folds, except for viral diseases of the anogenital area, which have well-known presentations, viral skin infections that have a special affinity to the skin folds are not known. Many viral exanthems may affect the skin folds during the course of the infection, but here we focus only on the ones that usually affect the fold areas and also on the less well-known conditions or recently described associations. PMID:26051057

  19. 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

  20. Tropism and Pathogenicity of Rickettsiae

    PubMed Central

    Uchiyama, Tsuneo

    2012-01-01

    Rickettsiae are obligate intracellular parasitic bacteria that cause febrile exanthematous illnesses such as Rocky Mountain spotted fever, Mediterranean spotted fever, epidemic, and murine typhus, etc. Although the vector ranges of each Rickettsia species are rather restricted; i.e., ticks belonging to Arachnida and lice and fleas belonging to Insecta usually act as vectors for spotted fever group (SFG) and typhus group (TG) rickettsiae, respectively, it would be interesting to elucidate the mechanisms controlling the vector tropism of rickettsiae. This review discusses the factors determining the vector tropism of rickettsiae. In brief, the vector tropism of rickettsiae species is basically consistent with their tropism toward cultured tick and insect cells. The mechanisms responsible for rickettsiae pathogenicity are also described. Recently, genomic analyses of rickettsiae have revealed that they possess several genes that are homologous to those affecting the pathogenicity of other bacteria. Analyses comparing the genomes of pathogenic and non-pathogenic strains of rickettsiae have detected many factors that are related to rickettsial pathogenicity. It is also known that a reduction in the rickettsial genome has occurred during the course of its evolution. Interestingly, Rickettsia species with small genomes, such as Rickettsia prowazekii, are more pathogenic to humans than those with larger genomes. This review also examines the growth kinetics of pathogenic and non-pathogenic species of SFG rickettsiae (SFGR) in mammalian cells. The growth of non-pathogenic species is restricted in these cells, which is mediated, at least in part, by autophagy. The superinfection of non-pathogenic rickettsiae-infected cells with pathogenic rickettsiae results in an elevated yield of the non-pathogenic rickettsiae and the growth of the pathogenic rickettsiae. Autophagy is restricted in these cells. These results are discussed in this review. PMID:22737150

  1. Portable pathogen detection system

    DOEpatents

    Colston, Billy W.; Everett, Matthew; Milanovich, Fred P.; Brown, Steve B.; 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.

  2. [Bioterrorism and pathogenic microorganisms].

    PubMed

    Schatzmayr, Hermann G; Barth, Ortrud Monika

    2013-10-01

    In recent years the use of pathogenic microorganisms in acts of bioterrorism has been the subject of major concern in many countries. This paper presents a possible application of viruses and bacteria for warfare and terrorist purposes, as well as a laboratory diagnosis to identify those agents. The viruses of smallpox (orthopoxvirus), of hemorrhagic fever and those belonging to filovirus have been highlighted, inter alia, as agents of human infection with bioterrorist intent. Among the bacteria, the emphasis has been on anthrax (Bacillus anthracis), the plague (Yersinia pestis), botulism (Clostridium botulinum) and tularemia (Francisella tularensis), not to mention ricin (Ricinus communis), as one of the Group B agents. PMID:24473660

  3. 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.

  4. 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

  5. Mitotic stability and nuclear inheritance of integrated viral cDNA in engineered hypovirulent strains of the chestnut blight fungus.

    PubMed Central

    Chen, B; Choi, G H; Nuss, D L

    1993-01-01

    Transmissible hypovirulence is a novel form of biological control in which virulence of a fungal pathogen is attenuated by an endogenous RNA virus. The feasibility of engineering hypovirulence was recently demonstrated by transformation of the chestnut blight fungus, Cryphonectria parasitica, with a full-length cDNA copy of a hypovirulence-associated viral RNA. Engineered hypovirulent transformants were found to contain both a chromsomally integrated cDNA copy of the viral genome and a resurrected cytoplasmically replicating double-stranded RNA form. We now report stable maintenance of integrated viral cDNA through repeated rounds of asexual sporulation and passages on host plant tissue. We also demonstrate stable nuclear inheritance of the integrated viral cDNA and resurrection of the cytoplasmic viral double-stranded RNA form in progeny resulting from the mating of an engineered hypovirulent C. parasitica strain and a vegetatively incompatible virulent strain. Mitotic stability of the viral cDNA ensures highly efficient transmission of the hypovirulence phenotype through conidia. Meiotic transmission, a mode not observed for natural hypovirulent strains, introduces virus into ascospore progeny representing a spectrum of vegetative compatibility groups, thereby circumventing barriers to anastomosis-mediated transmission imposed by the fungal vegetative incompatibility system. These transmission properties significantly enhance the potential of engineered hypovirulent C. parasitica strains as effective biocontrol agents. Images PMID:8344241

  6. Random mutagenesis in a plant viral genome using a DNA repair-deficient mutator Escherichia coli strain.

    PubMed

    Lu, X; Hirata, H; Yamaji, Y; Ugaki, M; Namba, S

    2001-05-01

    Random mutagenesis in a plant viral genome is valuable for generating attenuated strains or for analyzing viral gene function at the molecular level. A DNA repair-deficient mutator Escherichia coli strain was used for random mutagenesis of a plant viral genome. A full-length infectious cDNA clone of Citrus tatter leaf virus (genus Capillovirus) L strain (CTLV-L) genomic RNA under the T7 promoter sequence (pITCL) was introduced into the mutator E. coli strain XL1-Red and mutagenized overnight. To fix mutations, the mixture of plasmid DNA isolated from colonies of the mutator bacteria was introduced into another E. coli strain, JM109, which has normal DNA repair function. Infectious viral genomic RNA was transcribed in vitro from each mutagenized pITCL clone and inoculated on host plants. Phenotypic mutants were selected for altered pathogenicity in the inoculated plants. Nucleotide sequence analysis of each mutant revealed that mutations were introduced randomly into the CTLV-L genome regardless of the function of the viral gene. The nucleotide substitutions were biased towards single point mutations, which consisted of more transitions than transversions or single-base frameshifts. These mutations were preserved stably in plants subject to sequential mechanical inoculation. The strategy presented below is a simple and very efficient way to generate virus mutants for analyzing the functions of viral genes. PMID:11337038

  7. Mutational analysis reveals a noncontractile but interactive role of actin and profilin in viral RNA-dependent RNA synthesis.

    PubMed

    Harpen, Mary; Barik, Tiasha; Musiyenko, Alla; Barik, Sailen

    2009-11-01

    As obligatory parasites, viruses co-opt a variety of cellular functions for robust replication. The expression of the nonsegmented negative-strand RNA genome of respiratory syncytial virus (RSV), a significant pediatric pathogen, absolutely requires actin and is stimulated by the actin-regulatory protein profilin. As actin is a major contractile protein, it was important to determine whether the known functional domains of actin and profilin were important for their ability to activate RSV transcription. Analyses of recombinant mutants in a reconstituted RSV transcription system suggested that the divalent-cation-binding domain of actin is critically needed for binding to the RSV genome template and for the activation of viral RNA synthesis. In contrast, the nucleotide-binding domain and the N-terminal acidic domain were needed neither for template binding nor for transcription. Specific surface residues of actin, required for actin-actin contact during filamentation, were also nonessential for viral transcription. Unlike actin, profilin did not directly bind to the viral template but was recruited by actin. Mutation of the interactive residues of actin or profilin, resulting in the loss of actin-profilin binding, also abolished profilin's ability to stimulate viral transcription. Together, these results suggest that actin acts as a classical transcription factor for the virus by divalent-cation-dependent binding to the viral template and that profilin acts as a transcriptional cofactor, in part by associating with actin. This essential viral role of actin is independent of its contractile cellular role. PMID:19710142

  8. New Metrics for Evaluating Viral Respiratory Pathogenesis

    PubMed Central

    Menachery, Vineet D.; Gralinski, Lisa E.; Baric, Ralph S.; Ferris, Martin T.

    2015-01-01

    Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis. PMID:26115403

  9. Immunological memory to viral infection.

    PubMed

    Slifka, Mark K

    2004-08-01

    Immunological memory is defined by the ability of a host to remember a past encounter with a specific pathogen and to respond to it in an effective manner upon re-exposure. How long immunological memory can be maintained in the absence of re-infection continues to be a subject of great controversy. Recent studies on immunity following smallpox vaccination demonstrate that T-cell memory declines steadily with a half-life of 8-15 years, whereas antiviral antibody responses are maintained for up to 75 years without appreciable decline. By combining recent advances in quantitative immunology with historical accounts of protection against smallpox dating back to the time of Edward Jenner, we are gaining a better understanding of the duration and magnitude of immunological memory and how it relates to protective immunity. PMID:15245737

  10. Microarray analysis following infection with highly pathogenic avian influenza H5N1 virus in naive and vaccinated SPF chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) is a viral disease of poultry that remains a constant threat to commercial poultry throughout the world. Within the last few years, outbreaks of highly pathogenic avian influenza (HPAI) H5N1 have originated in Southeast Asia and spread to several European, Middle Eastern, and A...

  11. Unveiling time in dose-response models to infer host susceptibility to pathogens.

    PubMed

    Pessoa, Delphine; Souto-Maior, Caetano; Gjini, Erida; Lopes, Joao S; Ceña, Bruno; Codeço, Cláudia T; Gomes, M Gabriela M

    2014-08-01

    The biological effects of interventions to control infectious diseases typically depend on the intensity of pathogen challenge. As much as the levels of natural pathogen circulation vary over time and geographical location, the development of invariant efficacy measures is of major importance, even if only indirectly inferrable. Here a method is introduced to assess host susceptibility to pathogens, and applied to a detailed dataset generated by challenging groups of insect hosts (Drosophila melanogaster) with a range of pathogen (Drosophila C Virus) doses and recording survival over time. The experiment was replicated for flies carrying the Wolbachia symbiont, which is known to reduce host susceptibility to viral infections. The entire dataset is fitted by a novel quantitative framework that significantly extends classical methods for microbial risk assessment and provides accurate distributions of symbiont-induced protection. More generally, our data-driven modeling procedure provides novel insights for study design and analyses to assess interventions. PMID:25121762

  12. 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

  13. Evaluation of viral inactivation of pseudorabies virus, encephalomyocarditis virus, bovine viral diarrhea virus and porcine parvovirus in pancreatin of porcine origin.

    PubMed

    Caruso, C; Gobbi, E; Biosa, T; Andra', M; Cavallazzi, U; Masoero, L

    2014-11-01

    Pancreatin is a substance containing enzymes, principally amylase, lipase, and protease. It is obtained from bovine or porcine pancreas and used in the treatment of pancreatic endocrine insufficiency in humans. Regulations and safety concerns mandate viral clearance (virus removal or inactivation) in biopharmaceuticals such as pancreatin. A virus validation study was performed to evaluate virus clearance achieved in the final step of drying under vacuum by testing a panel of four animal viruses: Pseudorabies virus (PRV), Encephalomyocarditis virus (EMCV), Bovine viral diarrhea virus (BVDV), and Porcine parvovirus (PPV). Because of the product's virucidal effect and high cytotoxicity, the starting material was diluted to a ratio of 0.67 g of dried pancreatin resuspended in 13.5 mL of cell culture medium followed by a 50-fold dilution in cell culture medium before spiking. After heating at 60±1°C for 5 h, the samples were diluted about 5-fold in cell culture medium and titered by the plaque assay method. The virus reduction factor ranged from 5.59 (for PPV) to 7.07 (for EMCV) and no viral plaque was observed, indicating that the process step was effective in the reduction and removal of virus contamination. Though no virus contamination events in pancreatin have been reported to date, evaluation of the production process for its ability to inactivate and/or remove virus contamination, particularly from zoonotic viral agents such as hepatitis E virus and Norovirus considered emerging pathogens, is necessary to ensure the viral safety of animal-derived biopharmaceuticals. PMID:25110118

  14. Application of nucleic-acid-based therapeutics for viral infections in shrimp aquaculture.

    PubMed

    Shekhar, Mudagandur S; Lu, Yuanan

    2009-01-01

    Viral infections are one of the major reasons for the huge economic losses in shrimp farming. The control of viral diseases in shrimp remains a serious challenge for the shrimp aquacultural industry, with major pathogens, such as the white spot syndrome virus, yellow head virus, Taura syndrome virus, hepatopancreatic parvovirus, and baculoviruses, being geographically widespread. In the absence of a true adaptive immune response system in invertebrates such as shrimp, one of the alternative and more specific approaches to counteract viral infections in shrimp could be the use of molecular-based gene transfer technologies, such as RNA interference (RNAi). The RNAi mechanism is initiated by double-stranded RNAs (dsRNAs), which are fragmented into shorter 21-23 nucleotides of short interfering RNAs (siRNAs) by a type III endonuclease, the Dicer. RNAi, which is mediated by small interfering RNA (siRNA), results in the sequence-specific post-transcriptional silencing of a target gene. This gene-silencing mechanism is universally conserved and is a well-known phenomenon that exists in many eukaryotes, including invertebrates. It has been recently extended to shrimp as an important potential tool in viral disease prevention. RNAi technology shows considerable promise as a therapeutic approach and efficient strategy for shrimp virus control in the aquaculture industry. Further progress in understanding the mechanism of siRNAs at the molecular level, as well as strategies to achieve their tightly regulated, stable, prolonged and tissue-specific expression in an effective manner, will definitely revolutionize therapeutic approaches for counteracting viral diseases of shrimp. In the present review, the recent development and potential use of RNAi in combating shrimp viral infections is discussed. PMID:18941835

  15. 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...

  16. 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 ...

  17. Evaluation of novel carbon nano-tube particles in the bacterial and viral DNA and RNA extraction from the clinical samples

    Microsoft Academic Search

    Nguyen KC; Vo DXA; Hoang HN; Ho LTT; Pham HV

    2010-01-01

    Molecular techniques have become the most im- portant methods of detecting bacterial and viral pathogens. However, current genomic extraction methods are currently limited in term of automation. In this study, carbon nano-tube was used as the vector to trap DNA and RNA molecules. The capability of carbon nano-tube to trap DNA and RNA was evaluated using samples (TB and HBV

  18. Efficacy of the International Embryo Transfer Society (IETS) washing procedure for rendering oocytes matured in vitro free of bovine viral diarrhea virus (BVDV)

    Microsoft Academic Search

    A. Lalonde; A. Bielanski

    2011-01-01

    To ensure the freedom of embryos from pathogenic agents prior to embryo transfer (ET), a specific sanitary washing procedure has been recommended by the International Embryo Transfer Society (IETS). In the present study, the efficacy of removing the bovine viral diarrhea virus (BVDV) from cumulus-free matured oocytes at the stage of extruded first polar body (N = 240) was evaluated,

  19. 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

  20. A comprehensive collection of systems biology data characterizing the host response to viral infection

    PubMed Central

    Aevermann, Brian D.; Pickett, Brett E.; Kumar, Sanjeev; Klem, Edward B.; Agnihothram, Sudhakar; Askovich, Peter S.; Bankhead, Armand; Bolles, Meagen; Carter, Victoria; Chang, Jean; Clauss, Therese R.W.; Dash, Pradyot; Diercks, Alan H.; Eisfeld, Amie J.; Ellis, Amy; Fan, Shufang; Ferris, Martin T.; Gralinski, Lisa E.; Green, Richard R.; Gritsenko, Marina A.; Hatta, Masato; Heegel, Robert A.; Jacobs, Jon M.; Jeng, Sophia; Josset, Laurence; Kaiser, Shari M.; Kelly, Sara; Law, G. Lynn; Li, Chengjun; Li, Jiangning; Long, Casey; Luna, Maria L.; Matzke, Melissa; McDermott, Jason; Menachery, Vineet; Metz, Thomas O.; Mitchell, Hugh; Monroe, Matthew E.; Navarro, Garnet; Neumann, Gabriele; Podyminogin, Rebecca L.; Purvine, Samuel O.; Rosenberger, Carrie M.; Sanders, Catherine J.; Schepmoes, Athena A.; Shukla, Anil K.; Sims, Amy; Sova, Pavel; Tam, Vincent C.; Tchitchek, Nicolas; Thomas, Paul G.; Tilton, Susan C.; Totura, Allison; Wang, Jing; Webb-Robertson, Bobbie-Jo; Wen, Ji; Weiss, Jeffrey M.; Yang, Feng; Yount, Boyd; Zhang, Qibin; McWeeney, Shannon; Smith, Richard D.; Waters, Katrina M.; Kawaoka, Yoshihiro; Baric, Ralph; Aderem, Alan; Katze, Michael G.; Scheuermann, Richard H.

    2014-01-01

    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. PMID:25977790

  1. A comprehensive collection of systems biology data characterizing the host response to viral infection.

    PubMed

    Aevermann, Brian D; Pickett, Brett E; Kumar, Sanjeev; Klem, Edward B; Agnihothram, Sudhakar; Askovich, Peter S; Bankhead, Armand; Bolles, Meagen; Carter, Victoria; Chang, Jean; Clauss, Therese R W; Dash, Pradyot; Diercks, Alan H; Eisfeld, Amie J; Ellis, Amy; Fan, Shufang; Ferris, Martin T; Gralinski, Lisa E; Green, Richard R; Gritsenko, Marina A; Hatta, Masato; Heegel, Robert A; Jacobs, Jon M; Jeng, Sophia; Josset, Laurence; Kaiser, Shari M; Kelly, Sara; Law, G Lynn; Li, Chengjun; Li, Jiangning; Long, Casey; Luna, Maria L; Matzke, Melissa; McDermott, Jason; Menachery, Vineet; Metz, Thomas O; Mitchell, Hugh; Monroe, Matthew E; Navarro, Garnet; Neumann, Gabriele; Podyminogin, Rebecca L; Purvine, Samuel O; Rosenberger, Carrie M; Sanders, Catherine J; Schepmoes, Athena A; Shukla, Anil K; Sims, Amy; Sova, Pavel; Tam, Vincent C; Tchitchek, Nicolas; Thomas, Paul G; Tilton, Susan C; Totura, Allison; Wang, Jing; Webb-Robertson, Bobbie-Jo; Wen, Ji; Weiss, Jeffrey M; Yang, Feng; Yount, Boyd; Zhang, Qibin; McWeeney, Shannon; Smith, Richard D; Waters, Katrina M; Kawaoka, Yoshihiro; Baric, Ralph; Aderem, Alan; Katze, Michael G; Scheuermann, Richard H

    2014-01-01

    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. PMID:25977790

  2. A Rapid Method for Viral Particle Detection in Viral-Induced Gastroenteritis: A TEM Study

    NASA Astrophysics Data System (ADS)

    Hicks, M. John; Barrish, James P.; Hayes, Elizabeth S.; Leer, Laurie C.; Estes, Mary K.; Cubitt, W. D.

    1995-10-01

    Infectious gastroenteritis is a common cause of hospitalization in the pediatric population. The most frequent cause of gastroenteritis is viral in origin. The purpose of this study was to compare a rapid modified negative-staining TEM method with the conventional pseudoreplica technique in detection of viral particles in fecal samples from children with viral gastroenteritis. The modified negative-staining method resulted in a significantly higher (2.5 ± 0.5, p = 0.02) viral rating score than that for the conventional pseudoreplica technique (1.7 ± 0.4). In addition, the preparation time for the negative-staining method was approximately one fifth that for the conventional pseudoreplica technique. Rapid diagnosis of viral gastroenteritis may be made by ultrastructural detection of viral particles in fecal samples using the negative staining technique.

  3. 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.

  4. 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

  5. [Viral safety of biological medicinal products].

    PubMed

    Stühler, A; Blümel, J

    2014-10-01

    Viral safety of blood donations, plasma products, viral vaccines and gene therapy medicinal products, biotechnical-derived products and tissue and cell therapy products is a particular challenge. These products are manufactured using a variety of human or animal-derived starting materials and reagents; therefore, extensive testing of donors and of cell banks established for production is required. Furthermore, the viral safety of reagents, such as bovine sera, porcine trypsin and human transferrin or albumin needs to be considered. Whenever possible, manufacturing steps for inactivation or removal of viruses should be introduced; however, sometimes it is not possible to introduce such steps for tissues or cell-based medicinal products as the activity and viability of cells will be compromised. It might be possible to implement steps for inactivation or removal of potential contaminating enveloped viruses only for production of small and stable non-enveloped viral gene vectors. PMID:25123140

  6. 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.

  7. 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.

  8. Surveillance for Viral Hepatitis - United States, 2012

    MedlinePLUS

    ... Home Page Share Compartir Surveillance for Viral Hepatitis – United States, 2012 Entire report in a printable format [PDF - ... Reported cases of acute hepatitis A, by state ? United States, 2008–2012 Table 2.2 Clinical characteristics of ...

  9. 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

  10. Noninvasive visualization of respiratory viral infection using bioorthogonal conjugated near-infrared-emitting quantum dots.

    PubMed

    Pan, Hong; Zhang, Pengfei; Gao, Duyang; Zhang, Yijuan; Li, Ping; Liu, Lanlan; Wang, Ce; Wang, Hanzhong; Ma, Yifan; Cai, Lintao

    2014-06-24

    Highly pathogenic avian influenza A viruses are emerging pandemic threats in human beings. Monitoring the in vivo dynamics of avian influenza viruses is extremely important for understanding viral pathogenesis and developing antiviral drugs. Although a number of technologies have been applied for tracking viral infection in vivo, most of them are laborious with unsatisfactory detection sensitivity. Herein we labeled avian influenza H5N1 pseudotype virus (H5N1p) with near-infrared (NIR)-emitting QDs by bioorthogonal chemistry. The conjugation of QDs onto H5N1p was highly efficient with superior stability both in vitro and in vivo. Furthermore, QD-labeled H5N1p (QD-H5N1p) demonstrated bright and sustained fluorescent signals in mouse lung tissues, allowing us to visualize respiratory viral infection in a noninvasive and real-time manner. The fluorescence signals of QD-H5N1p in lung were correlated with the severity of virus infection and significantly attenuated by antiviral agents, such as oseltamivir carboxylate and mouse antiserum against H5N1p. The biodistribution of QD-H5N1p in lungs and other organs could be easily quantified by measuring fluorescent signals and cadmium concentration of virus-conjugated QDs in tissues. Hence, virus labeling with NIR QDs provides a simple, reliable, and quantitative strategy for tracking respiratory viral infection and for antiviral drug screening. PMID:24797178

  11. Defective interfering viruses and their impact on vaccines and viral vectors.

    PubMed

    Frensing, Timo

    2015-05-01

    Defective interfering particles (DIPs) have been found for many important viral pathogens and it is believed that most viruses generate DIPs. This article reviews the current knowledge of the generation and amplification of DIPs, which possess deletions in the viral genome but retain the ability to replicate in the presence of a complete helper virus. In addition, mechanisms are discussed by which DIPs interfere with the replication of their helper virus leading to the production of mainly progeny DIPs by coinfected cells. Even though DIPs cannot replicate on their own, they are biologically active and it is well known that they have a huge impact on virus replication, evolution, and pathogenesis. Moreover, defective genomes are potent inducers of the innate immune response. Yet, little attention has been paid to DIPs in recent years and their impact on biotechnological products such as vaccines and viral vectors remains elusive in most cases. With a focus on influenza virus, this review demonstrates that DIPs are important for basic research on viruses and for the production of viral vaccines and vectors. Reducing the generation and/or amplification of DIPs ensures reproducible results as well as high yields and consistent product quality in virus production. PMID:25728309

  12. 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

  13. Avian influenza H5N1 viral and bird migration networks in Asia

    PubMed Central

    Tian, Huaiyu; Zhou, Sen; Dong, Lu; Van Boeckel, Thomas P.; Cui, Yujun; Newman, Scott H.; Takekawa, John Y.; Prosser, Diann J.; Xiao, Xiangming; 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

  14. 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

  15. 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

  16. 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

  17. Emerging viral infections of the nervous system

    Microsoft Academic Search

    Richard T. Johnson

    2003-01-01

    New viral infections of the nervous system have been appearing with great regularity. Some result from the evolution of new\\u000a agents and others from the entry of viruses into new hosts or environments. The emergence of neurovirulent enteroviruses causing\\u000a a paralytic poliomyelitis syndrome and rhomboencephalitis represent the evolution of new human viruses. Most emerging viral\\u000a infections represent movement of an

  18. Viral Oncolysis for Malignant Liver Tumors

    Microsoft Academic Search

    John T. Mullen; Kenneth K. Tanabe

    2003-01-01

    Viral oncolysis represents a unique strategy to exploit the natural process of viral replication to kill tumor cells. Although\\u000a this concept dates back nearly a century, recent advances in the fields of molecular biology and virology have enabled investigators\\u000a to genetically engineer viruses with greater potency and tumor specificity. In this article we review the general mechanisms\\u000a by which oncolytic

  19. Natural Pathogens of Laboratory Mice, Rats, and Rabbits and Their Effects on Research

    PubMed Central

    Baker, David G.

    1998-01-01

    Laboratory mice, rats, and rabbits may harbor a variety of viral, bacterial, parasitic, and fungal agents. Frequently, these organisms cause no overt signs of disease. However, many of the natural pathogens of these laboratory animals may alter host physiology, rendering the host unsuitable for many experimental uses. While the number and prevalence of these pathogens have declined considerably, many still turn up in laboratory animals and represent unwanted variables in research. Investigators using mice, rats, and rabbits in biomedical experimentation should be aware of the profound effects that many of these agents can have on research. PMID:9564563

  20. Next Generation Respiratory Viral Vaccine System: Advanced and Emerging Bioengineered Human Lung Epithelia Model (HLEM) Organoid Technology

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J.; Schneider, Sandra L.; MacIntosh, Victor; Gibbons, Thomas F.

    2010-01-01

    Acute respiratory infections, including pneumonia and influenza, are the S t" leading cause of United States and worldwide deaths. Newly emerging pathogens signaled the need for an advanced generation of vaccine technology.. Human bronchial-tracheal epithelial tissue was bioengineered to detect, identify, host and study the pathogenesis of acute respiratory viral disease. The 3-dimensional (3D) human lung epithelio-mesechymal tissue-like assemblies (HLEM TLAs) share characteristics with human respiratory epithelium: tight junctions, desmosomes, microvilli, functional markers villin, keratins and production of tissue mucin. Respiratory Syntial Virus (RSV) studies demonstrate viral growth kinetics and membrane bound glycoproteins up to day 20 post infection in the human lung-orgainoid infected cell system. Peak replication of RSV occurred on day 10 at 7 log10 particles forming units per ml/day. HLEM is an advanced virus vaccine model and biosentinel system for emergent viral infectious diseases to support DoD global surveillance and military readiness.

  1. Pediatric knowledge about acute viral hepatitis.

    PubMed

    Franca, Rita; Silva, Luciana; Melo, Maria Clotildes; Cavalcante, Suzy; Lima, Bruno; Rocha, Anita; Gomes, Cristiana; Franca, Mônica

    2004-06-01

    Knowledge about hepatotropic viruses is crucial for pediatricians because of the high prevalence of viral hepatitis during childhood. The multiplicity of hepatotropic viruses, the spectrum of acute and chronic infections, and the sequels of viral hepatitis result in a need for physicians to better understand the clinical and epidemiological context of patients with viral hepatitis, as well as the importance of prevention measures for hepatitis. A descriptive cross-sectional study was made of pediatrician's knowledge about viral hepatitis, through questionnaires to 574 pediatricians, with no obligation of identification. The pediatricians were recruited among those who attended a national Congress of Pediatrics in Brasília, Brazil. Among these pediatricians, 50.1% frequently treated cases of hepatitis, and 74.7% indicated that they had knowledge of the existence of five hepatotropic viruses; 14.5% knew about at least four types of hepatitis complications, while only 7.7% and 4.3% were able to correctly diagnose viral hepatitis A and B, respectively. Many (28.4%) did not know how to treat the patients adequately. Only 37.5% had already recommended vaccination against hepatitis B. Only 50.2% of the pediatricians had been vaccinated against hepatitis B. We concluded that it is crucial to make pediatricians more knowledgeable about viral hepatitis, through continued education programs, especially emphasizing prevention procedures. PMID:15476061

  2. 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.

  3. Development and Application of Quantitative Detection Method for Viral Hemorrhagic Septicemia Virus (VHSV) Genogroup IVa

    PubMed Central

    Kim, Jong-Oh; Kim, Wi-Sik; Kim, Si-Woo; Han, Hyun-Ja; Kim, Jin Woo; Park, Myoung Ae; Oh, Myung-Joo

    2014-01-01

    Viral hemorrhagic septicemia virus (VHSV) is a problematic pathogen in olive flounder (Paralichthys olivaceus) aquaculture farms in Korea. Thus, it is necessary to develop a rapid and accurate diagnostic method to detect this virus. We developed a quantitative RT-PCR (qRT-PCR) method based on the nucleocapsid (N) gene sequence of Korean VHSV isolate (Genogroup IVa). The slope and R2 values of the primer set developed in this study were ?0.2928 (96% efficiency) and 0.9979, respectively. Its comparison with viral infectivity calculated by traditional quantifying method (TCID50) showed a similar pattern of kinetic changes in vitro and in vivo. The qRT-PCR method reduced detection time compared to that of TCID50, making it a very useful tool for VHSV diagnosis. PMID:24859343

  4. Development and application of quantitative detection method for viral hemorrhagic septicemia virus (VHSV) genogroup IVa.

    PubMed

    Kim, Jong-Oh; Kim, Wi-Sik; Kim, Si-Woo; Han, Hyun-Ja; Kim, Jin Woo; Park, Myoung Ae; Oh, Myung-Joo

    2014-05-01

    Viral hemorrhagic septicemia virus (VHSV) is a problematic pathogen in olive flounder (Paralichthys olivaceus) aquaculture farms in Korea. Thus, it is necessary to develop a rapid and accurate diagnostic method to detect this virus. We developed a quantitative RT-PCR (qRT-PCR) method based on the nucleocapsid (N) gene sequence of Korean VHSV isolate (Genogroup IVa). The slope and R² values of the primer set developed in this study were -0.2928 (96% efficiency) and 0.9979, respectively. Its comparison with viral infectivity calculated by traditional quantifying method (TCID??) showed a similar pattern of kinetic changes in vitro and in vivo. The qRT-PCR method reduced detection time compared to that of TCID??, making it a very useful tool for VHSV diagnosis. PMID:24859343

  5. The interaction between viral protein and host actin facilitates the virus infection to host.

    PubMed

    Yang, Geng; Xiao, Xiao; Yin, Dongsheng; Zhang, Xiaobo

    2012-10-10

    Although the virus-host interaction has attracted extensive studies, the host proteins essential for virus infection remain largely unknown. To address this issue, the shrimp Penaeus stylirostris densovirus (PstDNV), belonging to the family Parvoviridae, was characterized. PstDNV, a single-stranded DNA virus with a 3.9-kb genome, encoded only three open reading frames (ORFs). Among the three viral proteins, the PstDNV ORF2-encoded protein was discovered to interact with the shrimp actin, suggesting that the host actin played a very important role in virus infection. The RNAi assays revealed that the ORF2-encoded protein was required for the PstDNV infection. The confocal evidence demonstrated that the interaction between the ORF2-encoded protein and actin was essential for the virus infection. Therefore our study indicated that the manipulation of the host actin cytoskeleton was a necessary strategy for viral pathogens to invade host cells. PMID:22750318

  6. Recent insights into the role of Toll-like receptors in viral infection

    PubMed Central

    Carty, M; Bowie, A G

    2010-01-01

    Toll-like receptors (TLRs) have a central role in innate immunity as they detect conserved pathogen-associated molecular patterns (PAMPs) on a range of microbes, including viruses, leading to innate immune activation and orchestration of the adaptive immune response. To date, a large number of viruses have been shown to trigger innate immunity via TLRs, suggesting that these receptors are likely to be important in the outcome to viral infection. This suggestion is supported by the observation that many viruses have evolved mechanisms not only to evade the innate immune system, but also to subvert it for the benefit of the virus. In this review we will discuss earlier evidence, mainly from knock-out mice studies, implicating TLRs in the innate immune response to viruses, in light of more recent clinical data demonstrating that TLRs are important for anti-viral immunity in humans. PMID:20560984

  7. Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein

    PubMed Central

    Belouzard, Sandrine; Millet, Jean K.; Licitra, Beth N.; Whittaker, Gary R.

    2012-01-01

    Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. It is classified as a class I fusion protein, and is responsible for binding to the receptor on the host cell as well as mediating the fusion of host and viral membranes—A process driven by major conformational changes of the S protein. This review discusses coronavirus entry mechanisms focusing on the different triggers used by coronaviruses to initiate the conformational change of the S protein: receptor binding, low pH exposure and proteolytic activation. We also highlight commonalities between coronavirus S proteins and other class I viral fusion proteins, as well as distinctive features that confer distinct tropism, pathogenicity and host interspecies transmission characteristics to coronaviruses. PMID:22816037

  8. Model of influenza A virus infection: dynamics of viral antagonism and innate immune response

    PubMed Central

    Fribourg, M.; Hartmann, B.; Schmolke, M.; Marjanovic, N.; Albrecht, R.A.; García-Sastre, A.; Sealfon, S. C.; Jayaprakash, C.; Hayot, F.

    2014-01-01

    Viral antagonism of host responses is an essential component of virus pathogenicity. The study of the interplay between immune response and viral antagonism is challenging due to the involvement of many processes acting at multiple time scales. Here we develop an ordinary differential equation model to investigate the early, experimentally-measured, responses of human monocyte-derived dendritic cells to infection by two H1N1 influenza A viruses of different clinical outcome: pandemic A/California/4/2009 and seasonal A/New Caledonia/20/1999. Our results reveal how the strength of virus antagonism, and the time scale over which it acts to thwart the innate immune response, differ significantly between the two viruses, as is made clear by their impact on the temporal behavior of a number of measured genes. The model thus sheds light on the mechanisms that underlie the variability of innate immune responses to different H1N1 viruses. PMID:24594370

  9. A bio-synthetic interface for discovery of viral entry mechanisms.

    SciTech Connect

    Gutzler, Mike; Maar, Dianna; Negrete, Oscar; Hayden, Carl C.; Sasaki, Darryl Yoshio; Stachowiak, Jeanne C.; Wang, Julia

    2010-09-01

    Understanding and defending against pathogenic viruses is an important public health and biodefense challenge. The focus of our LDRD project has been to uncover the mechanisms enveloped viruses use to identify and invade host cells. We have constructed interfaces between viral particles and synthetic lipid bilayers. This approach provides a minimal setting for investigating the initial events of host-virus interaction - (i) recognition of, and (ii) entry into the host via membrane fusion. This understanding could enable rational design of therapeutics that block viral entry as well as future construction of synthetic, non-proliferating sensors that detect live virus in the environment. We have observed fusion between synthetic lipid vesicles and Vesicular Stomatitis virus particles, and we have observed interactions between Nipah virus-like particles and supported lipid bilayers and giant unilamellar vesicles.

  10. Rift Valley Fever Virus Nonstructural Protein NSs Promotes Viral RNA Replication and Transcription in a Minigenome System

    Microsoft Academic Search

    Tetsuro Ikegami; C. J. Peters; Shinji Makino

    2005-01-01

    Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family Bunyaviridae, has a tripartite negative-strand genome (S, M, and L segments) and is an important mosquito-borne pathogen for domestic animals and humans. We established an RVFV T7 RNA polymerase-driven minigenome system in which T7 RNA polymerase from an expression plasmid drove expression of RNA transcripts for viral proteins

  11. Vaccination of cattle with a DNA plasmid encoding the bovine viral diarrhoea virus major glycoprotein E2

    Microsoft Academic Search

    Serge Harpin; David J. Hurley; Majambu Mbikay; Brian Talbot; Youssef Elazhary

    Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle that is ubiquitously distributed worldwide. In this study, cattle were immunized by intramuscular injections with plasmid DNA expressing the BVDV type 1 major glycoprotein E2. Animals either received injections of naked DNA (N-DNA) or DNA in cationic liposomes (L-DNA). Both DNA preparations induced virus-specific neutralizing antibodies in vaccinates,

  12. Immunodominant viral peptides as determinants of cross-reactivity in the immune system--Can we develop wide spectrum viral vaccines?

    PubMed

    Vieira, G F; Chies, J A B

    2005-01-01

    When we look back to Edward Jenner vaccination of a young man in 1796, we cannot help thinking that he was both lucky and crazy. Crazy because he decided to test in a human being a hypothesis based mainly in the traditional belief that people who had acquired cowpox from the udders of a cow were thereafter resistant to smallpox, a quite devastating disease, and lucky because (even considering that he did not know this at that time) he succeeded to induce protection against a pathogen through the induction of an immune response directed against a different agent. Not only was he able to protect the young man but he took the first step towards the development of a vast new field, vaccination. It is acceptable to say that Jenner was lucky because he succeeded in promoting protection against smallpox using a cowpox virus and this induction of protection in a cross-reactive way is believed to be quite rare. Nevertheless, more and more examples of cross-reactive immune responses are being described and we are beginning to admit that cross-reactivity is far more common and important than we used to think. Here we review cross-reactivity in the immune system and the plasticity of T cell recognition. Based on the existence of T cell receptor promiscuous recognition and cross-recognition of conserved viral immunodominant epitopes, we propose two approaches to develop wide spectrum viral vaccines. The first one is based on the identification, characterization, and cloning of immunodominant viral epitopes able to stimulate responses against different viruses. The produced peptides could then be purified and serve as a basis for vaccine therapies. A second strategy is based on the identification of conserved patterns in immunodominant viral peptides and the production of synthetic peptides containing the amino acid residues necessary for MHC anchoring and TCR contact. Although we are still far from a complete knowledge of the cross-reactivity phenomenon in the immune system, the analysis of immunodominant viral epitopes and the identification of particular "viral patterns" seems to be important steps towards the development of wide spectrum viral vaccines. PMID:16051445

  13. Pathogenic agents in freshwater resources

    NASA Astrophysics Data System (ADS)

    Geldreich, Edwin E.

    1996-02-01

    Numerous pathogenic agents have been found in freshwaters used as sources for water supplies, recreational bathing and irrigation. These agents include bacterial pathogens, enteric viruses, several protozoans and parasitic worms more common to tropical waters. Although infected humans are a major source of pathogens, farm animals (cattle, sheep, pigs), animal pets (dogs, cats) and wildlife serve as significant reservoirs and should not be ignored. The range of infected individuals within a given warm-blooded animal group (humans included) may range from 1 to 25%. Survival times for pathogens in the water environment may range from a few days to as much as a year (Ascaris, Taenia eggs), with infective dose levels varying from one viable cell for several primary pathogenic agents to many thousands of cells for a given opportunistic pathogen.As pathogen detection in water is complex and not readily incorporated into routine monitoring, a surrogate is necessary. In general, indicators of faecal contamination provide a positive correlation with intestinal pathogen occurrences only when appropriate sample volumes are examined by sensitive methodology.Pathways by which pathogens reach susceptible water users include ingestion of contaminated water, body contact with polluted recreational waters and consumption of salad crops irrigated by polluted freshwaters. Major contributors to the spread of various water-borne pathogens are sewage, polluted surface waters and stormwater runoff. All of these contributions are intensified during periods of major floods. Several water-borne case histories are cited as examples of breakdowns in public health protection related to water supply, recreational waters and the consumption of contaminated salad crops. In the long term, water resource management must focus on pollution prevention from point sources of waste discharges and the spread of pathogens in watershed stormwater runoff.

  14. Viral Perturbations of Host Networks Reflect Disease Etiology

    Microsoft Academic Search

    Natali Gulbahce; Han Yan; Amélie Dricot; Megha Padi; Danielle Byrdsong; Rachel Franchi; Deok-Sun Lee; Orit Rozenblatt-Rosen; Jessica C. Mar; Michael A. Calderwood; Amy Baldwin; Bo Zhao; Balaji Santhanam; Pascal Braun; Nicolas Simonis; Kyung-Won Huh; Karin Hellner; Miranda Grace; Alyce Chen; Renee Rubio; Jarrod A. Marto; Nicholas A. Christakis; Elliott Kieff; Frederick P. Roth; Jennifer Roecklein-Canfield; James A. DeCaprio; Michael E. Cusick; John Quackenbush; David E. Hill; Karl Münger; Marc Vidal; Albert-László Barabási

    2012-01-01

    Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus

  15. Fungal pathogens of Proteaceae.

    PubMed

    Crous, P W; Summerell, B A; Swart, L; Denman, S; Taylor, J E; Bezuidenhout, C M; Palm, M E; Marincowitz, S; Groenewald, J Z

    2011-12-01

    Species of Leucadendron, Leucospermum and Protea (Proteaceae) are in high demand for the international floriculture market due to their brightly coloured and textured flowers or bracts. Fungal pathogens, however, create a serious problem in cultivating flawless blooms. The aim of the present study was to characterise several of these pathogens using morphology, culture characteristics, and DNA sequence data of the rRNA-ITS and LSU genes. In some cases additional genes such as TEF 1-? and CHS were also sequenced. Based on the results of this study, several novel species and genera are described. Brunneosphaerella leaf blight is shown to be caused by three species, namely B. jonkershoekensis on Protea repens, B. nitidae sp. nov. on Protea nitida and B. protearum on a wide host range of Protea spp. (South Africa). Coniothyrium-like species associated with Coniothyrium leaf spot are allocated to other genera, namely Curreya grandicipis on Protea grandiceps, and Microsphaeropsis proteae on P. nitida (South Africa). Diaporthe leucospermi is described on Leucospermum sp. (Australia), and Diplodina microsperma newly reported on Protea sp. (New Zealand). Pyrenophora blight is caused by a novel species, Pyrenophora leucospermi, and not Drechslera biseptata or D. dematoidea as previously reported. Fusicladium proteae is described on Protea sp. (South Africa), Pestalotiopsis protearum on Leucospermum cuneiforme (Zimbabwe), Ramularia vizellae and R. stellenboschensis on Protea spp. (South Africa), and Teratosphaeria capensis on Protea spp. (Portugal, South Africa). Aureobasidium leaf spot is shown to be caused by two species, namely A. proteae comb. nov. on Protea spp. (South Africa), and A. leucospermi sp. nov. on Leucospermum spp. (Indonesia, Portugal, South Africa). Novel genera and species elucidated in this study include Gordonomyces mucovaginatus and Pseudopassalora gouriqua (hyphomycetes), and Xenoconiothyrium catenata (coelomycete), all on Protea spp. (South Africa). PMID:22403475

  16. Viral suppressors of the RIG-I-mediated interferon response are pre-packaged in influenza virions

    PubMed Central

    Liedmann, Swantje; Hrincius, Eike R.; Guy, Cliff; Anhlan, Darisuren; Dierkes, Rüdiger; Carter, Robert; Wu, Gang; Staeheli, Peter; Green, Douglas R.; Wolff, Thorsten; McCullers, Jonathan A.; Ludwig, Stephan; Ehrhardt, Christina

    2014-01-01

    The type I interferon (IFN) response represents the first line of defence to invading pathogens. Internalized viral ribonucleoproteins (vRNPs) of negative-strand RNA viruses induce an early IFN response by interacting with retinoic acid inducible gene I (RIG-I) and its recruitment to mitochondria. Here we employ three-dimensional stochastic optical reconstruction microscopy (STORM) to visualize incoming influenza A virus (IAV) vRNPs as helical-like structures associated with mitochondria. Unexpectedly, an early IFN induction in response to vRNPs is not detected. A distinct amino-acid motif in the viral polymerases, PB1/PA, suppresses early IFN induction. Mutation of this motif leads to reduced pathogenicity in vivo, whereas restoration increases it. Evolutionary dynamics in these sequences suggest that completion of the motif, combined with viral reassortment can contribute to pandemic risks. In summary, inhibition of the immediate anti-viral response is ‘pre-packaged’ in IAV in the sequences of vRNP-associated polymerase proteins. PMID:25487526

  17. Viral suppressors of the RIG-I-mediated interferon response are pre-packaged in influenza virions.

    PubMed

    Liedmann, Swantje; Hrincius, Eike R; Guy, Cliff; Anhlan, Darisuren; Dierkes, Rüdiger; Carter, Robert; Wu, Gang; Staeheli, Peter; Green, Douglas R; Wolff, Thorsten; McCullers, Jonathan A; Ludwig, Stephan; Ehrhardt, Christina

    2014-01-01

    The type I interferon (IFN) response represents the first line of defence to invading pathogens. Internalized viral ribonucleoproteins (vRNPs) of negative-strand RNA viruses induce an early IFN response by interacting with retinoic acid inducible gene I (RIG-I) and its recruitment to mitochondria. Here we employ three-dimensional stochastic optical reconstruction microscopy (STORM) to visualize incoming influenza A virus (IAV) vRNPs as helical-like structures associated with mitochondria. Unexpectedly, an early IFN induction in response to vRNPs is not detected. A distinct amino-acid motif in the viral polymerases, PB1/PA, suppresses early IFN induction. Mutation of this motif leads to reduced pathogenicity in vivo, whereas restoration increases it. Evolutionary dynamics in these sequences suggest that completion of the motif, combined with viral reassortment can contribute to pandemic risks. In summary, inhibition of the immediate anti-viral response is 'pre-packaged' in IAV in the sequences of vRNP-associated polymerase proteins. PMID:25487526

  18. Evaluation of the Universal Viral Transport system for long-term storage of virus specimens for microbial forensics.

    PubMed

    Hosokawa-Muto, Junji; Fujinami, Yoshihito; Mizuno, Natsuko

    2015-08-01

    Forensic microbial specimens, including bacteria and viruses, are collected at biocrime and bioterrorism scenes. Although it is preferable that the pathogens in these samples are alive and kept in a steady state, the samples may be stored for prolonged periods before analysis. Therefore, it is important to understand the effects of storage conditions on the pathogens contained within such samples. To evaluate the capacity to preserve viable virus and the viral genome, influenza virus was added to the transport medium of the Universal Viral Transport system and stored for over 3 months at various temperatures, after which virus titrations and quantitative analysis of the influenza hemagglutinin gene were performed. Although viable viruses became undetectable 29 days after the medium was stored at room temperature, viruses in the medium stored at 4 °C were viable even after 99 days. A quantitative PCR analysis indicated that the hemagglutinin gene was maintained for 99 days at both 4 °C and room temperature. Therefore, long-term storage at 4 °C has little effect on viable virus and viral genes, so the Universal Viral Transport system can be useful for microbial forensics. This study provides important information for the handling of forensic virus specimens. PMID:26165655

  19. USEPA PATHOGEN EQUIVALENCY COMMITTEE RETREAT

    EPA Science Inventory

    The Pathogen Equivalency Committee held its retreat from September 20-21, 2005 at Hueston Woods State Park in College Corner, Ohio. This presentation will update the PEC’s membership on emerging pathogens, analytical methods, disinfection techniques, risk analysis, preparat...

  20. New trends in emerging pathogens

    Microsoft Academic Search

    Niels Skovgaard

    2007-01-01

    The emergence of pathogens is the result of a number of impact in all parts of the food chain.The emerging technologies in food production explain how new pathogens can establish themselves in the food chain and compromise food safety. The impact of the food technology is analysed for several bacteria, such as Yersinia, Campylobacter, Arcobacter, Helicobacter pullorum, Enterobacter sakazakii, Mycobacterium

  1. Common themes in microbial pathogenicity.

    PubMed Central

    Finlay, B B; Falkow, S

    1989-01-01

    A bacterial pathogen is a highly adapted microorganism which has the capacity to cause disease. The mechanisms used by pathogenic bacteria to cause infection and disease usually include an interactive group of virulence determinants, sometimes coregulated, which are suited for the interaction of a particular microorganism with a specific host. Because pathogens must overcome similar host barriers, common themes in microbial pathogenesis have evolved. However, these mechanisms are diverse between species and not necessarily conserved; instead, convergent evolution has developed several different mechanisms to overcome host barriers. The success of a bacterial pathogen can be measured by the degree with which it replicates after entering the host and reaching its specific niche. Successful microbial infection reflects persistence within a host and avoidance or neutralization of the specific and nonspecific defense mechanisms of the host. The degree of success of a pathogen is dependent upon the status of the host. As pathogens pass through a host, they are exposed to new environments. Highly adapted pathogenic organisms have developed biochemical sensors exquisitely designed to measure and respond to such environmental stimuli and accordingly to regulate a cascade of virulence determinants essential for life within the host. The pathogenic state is the product of dynamic selective pressures on microbial populations. PMID:2569162

  2. Structural engineering of a phage lysin that targets Gram-negative pathogens

    Microsoft Academic Search

    Petra Lukacik; Travis J. Barnard; Paul W. Keller; Kaveri S. Chaturvedi; Nadir Seddiki; James W. Fairman; Nicholas Noinaj; Tara L. Kirby; Jeffrey P. Henderson; Alasdair C. Steven; B. Joseph Hinnebusch; Susan K. Buchanan

    2012-01-01

    Bacterial pathogens are becoming increasingly resistant to antibiotics. As an alternative therapeutic strategy, phage therapy reagents containing purified viral lysins have been developed against Gram-positive organisms but not against Gram-negative organisms due to the inability of these types of drugs to cross the bacterial outer membrane. We solved the crystal structures of a Yersinia pestis outer membrane transporter called FyuA

  3. The Aromatic Domain of the Coronavirus Class I Viral Fusion Protein Induces Membrane Permeabilization: Putative Role during Viral Entry

    E-print Network

    Wimley, William C.

    animal viruses requires fusion between the viral membrane and a cellular membrane, either the plasma) glycoprotein, a class I viral fusion protein. During viral and target cell membrane fusion, the heptad repeat to drive apposition and subsequent fusion of viral and target cell membranes; however, the exact mechanism

  4. Viral loads in clinical specimens and SARS manifestations.

    PubMed

    Hung, I F N; Lau, S K P; Woo, P C Y; Yuen, K Y

    2009-12-01

    1. A high viral load in nasopharyngeal aspirate (with or without a high viral load in serum) is a useful prognostic indicator of respiratory failure or mortality. The presence of viral RNA in multiple body sites is also indicative of poor prognosis. 2. Early treatment with an effective antiviral agent before day 10 may decrease the peak viral load, and thus ameliorate the clinical symptoms and mortality, and reduce viral shedding and the risk of transmission PMID:20393220

  5. Direct Sequence Detection of Structured H5 Influenza Viral RNA

    PubMed Central

    Kerby, Matthew B.; Freeman, Sarah; Prachanronarong, Kristina; Artenstein, Andrew W.; Opal, Steven M.; Tripathi, Anubhav

    2008-01-01

    We describe the development of sequence-specific molecular beacons (dual-labeled DNA probes) for identification of the H5 influenza subtype, cleavage motif, and receptor specificity when hybridized directly with in vitro transcribed viral RNA (vRNA). The cloned hemagglutinin segment from a highly pathogenic H5N1 strain, A/Hanoi/30408/2005(H5N1), isolated from humans was used as template for in vitro transcription of sense-strand vRNA. The hybridization behavior of vRNA and a conserved subtype probe was characterized experimentally by varying conditions of time, temperature, and Mg2+ to optimize detection. Comparison of the hybridization rates of probe to DNA and RNA targets indicates that conformational switching of influenza RNA structure is a rate-limiting step and that the secondary structure of vRNA dominates the binding kinetics. The sensitivity and specificity of probe recognition of other H5 strains was calculated from sequence matches to the National Center for Biotechnology Information influenza database. The hybridization specificity of the subtype probes was experimentally verified with point mutations within the probe loop at five locations corresponding to the other human H5 strains. The abundance frequencies of the hemagglutinin cleavage motif and sialic acid recognition sequences were experimentally tested for H5 in all host viral species. Although the detection assay must be coupled with isothermal amplification on the chip, the new probes form the basis of a portable point-of-care diagnostic device for influenza subtyping. PMID:18403607

  6. Experimentally-induced immune activation in natural hosts of SIV induces significant increases in viral replication and CD4+ T cell depletion

    SciTech Connect

    Ribeiro, Ruy M [Los Alamos National Laboratory

    2008-01-01

    Chronically SIVagm-infected African green monkeys (AGMs) have a remarkably stable non-pathogenic disease course, with levels of immune activation in chronic SIVagm infection similar to those observed in uninfected monkeys and stable viral loads (VLs) for long periods of time. In vivo administration of lipopolysaccharide (LPS) or an IL-2/diphtheria toxin fusion protein (Ontak) to chronically SIVagm-infected AGMs triggered increases in immune activation and subsequently of viral replication and depletion of intestinal CD4{sup +} T cells. Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating that immune activation and T cell prolifeation are key factors in AIDS pathogenesis.

  7. Oncolytic Viral Therapy Using Reovirus.

    PubMed

    Thirukkumaran, Chandini; Morris, Don G

    2015-01-01

    Current mainstays in cancer treatment such as chemotherapy, radiation therapy, hormonal manipulation, and even targeted therapies such as Trastuzumab (herceptin) for breast cancer or Iressa (gefitinib) for non-small cell lung cancer among others are limited by lack of efficacy, cellular resistance, and toxicity. Dose escalation and combination therapies designed to overcome resistance and increase efficacy are limited by a narrow therapeutic index. Oncolytic viruses are one such group of new biological therapeutics that appears to have a wide spectrum of anticancer activity with minimal human toxicity.Since the malignant phenotype of tumors is the culmination of multiple mutations that occur in genes eventually leading to aberrant signaling pathways, oncolytic viruses either natural or engineered specifically target tumor cells taking advantage of this abnormal cellular signaling for their replication. Reovirus is one such naturally occurring double-stranded RNA virus that exploits altered signaling pathways (including Ras) in a myriad of cancers. The ability of reovirus to infect and lyse tumors under in vitro, in vivo, and ex vivo conditions has been well documented previously by us and others. The major mechanism of reovirus oncolysis of cancer cells has been shown to occur through apoptosis with autophagy taking place during this process in certain cancers. In addition, the synergistic antitumor effects of reovirus in combination with radiation or chemotherapy have also been demonstrated for reovirus resistant and moderately sensitive tumors. Recent progress in our understanding of viral immunology in the tumor microenvironment has diverted interest in exploring immunologic mechanisms to overcome resistance exhibited by chemotherapeutic drugs in cancer. Thus, currently several investigations are focusing on immune potentiating of reovirus for maximal tumor targeting. This chapter therefore has concentrated on immunologic cell death induction with reovirus as a novel approach to cancer therapy used under in vitro and in vivo conditions, as well as in a clinical setting. Reovirus phase I clinical trials have shown indications of efficacy, and several phase II/III trials are ongoing at present. Reovirus's extensive preclinical efficacy, replication competency, and low toxicity profile in humans have placed it as an attractive anticancer therapeutic for ongoing clinical testing that are highlighted in this chapter. PMID:26072409

  8. Disseminated Bovine viral diarrhea virus in a persistently infected alpaca (Vicugna pacos) cria.

    PubMed

    Byers, Stacey R; Snekvik, Kevin R; Righter, Daniel J; Evermann, James F; Bradway, Daniel S; Parish, Steven M; Barrington, George M

    2009-01-01

    Bovine viral diarrhea virus (BVDV) is an emerging infectious pathogen of concern to the alpaca industry. A 4-month-old, intact, male alpaca cria was diagnosed as persistently infected with BVDV on the basis of repeated positive antemortem polymerase chain reaction (PCR) and virus isolation (VI) assays and negative serologic titers to BVDV. Immunohistochemistry, real-time reverse transcription PCR, and VI performed on tissues collected at necropsy demonstrated disseminated BVDV-1b infection. Virus was detected in multiple tissues, including parotid salivary gland, testes, prostate, kidneys, skin, and gastrointestinal tract. Demonstration of BVDV in previously unreported tissues suggests additional potential routes of BVDV transmission in alpacas. PMID:19139518

  9. Molecular piracy: the viral link to carcinogenesis.

    PubMed

    Flaitz, C M; Hicks, M J

    1998-11-01

    The vast majority of the human experience with viral infections is associated with acute symptoms, such as malaise, fever, chills, rhinitis and diarrhea. With this acute or lytic phase, the immune system mounts a response and eliminates the viral agent while acquiring antibodies to that specific viral subtype. With latent or chronic infections, the viral agent becomes incorporated into the human genome. Viral agents capable of integration into the host's genetic material are particularly dangerous and may commandeer the host's ability to regulate normal cell growth and proliferation. The oncogenic viruses may immortalize the host cell, and facilitate malignant transformation. Cell growth and proliferation may be enhanced by viral interference with tumor suppressor gene function (p53 and pRb). Viruses may act as vectors for mutated proto-oncogenes (oncogenes). Overexpression of these oncogenes in viral-infected cells interferes with normal cell function and allows unregulated cell growth and proliferation, which may lead to malignant transformation and tumour formation. Development of oral neoplasms, both benign and malignant, has been linked to several viruses. Epstein-Barr virus is associated with oral hairy leukoplakia, lymphoproliferative disease, lymphoepithelial carcinoma, B-cell lymphomas, and nasopharyngeal carcinoma. Human herpesvirus-8 has been implicated in all forms of Kaposi's sarcoma, primary effusion lymphomas, multiple myeloma, angioimmunoblastic lymphadenopathy, and Castleman's disease. Human herpesvirus-6 has been detected in lymphoproliferative disease, lymphomas, Hodgkin's disease, and oral squamous cell carcinoma. The role of human papillomavirus in benign (squamous papilloma, focal epithelial hyperplasia, condyloma acuminatum, verruca vulgaris), premalignant (oral epithelial dysplasia), and malignant (squamous cell carcinoma) neoplasms within the oral cavity is well recognized. Herpes simplex virus may participate as a cofactor in oral squamous cell carcinoma development by enhancing activation, amplification, and overexpression of pre-existing oncogenes within neoplastic tissues. Because of the integral role of viruses in malignant transformation of host cells, innovative antiviral therapy may prevent tumour development, involute neoplastic proliferations, or arrest malignant progression. PMID:9930354

  10. Dicer-2 Processes Diverse Viral RNA Species

    PubMed Central

    Sabin, Leah R.; Zheng, Qi; Thekkat, Pramod; Yang, Jamie; Hannon, Gregory J.; Gregory, Brian D.; Tudor, Matthew; Cherry, Sara

    2013-01-01

    RNA silencing pathways play critical roles in gene regulation, virus infection, and transposon control. RNA interference (RNAi) is mediated by small interfering RNAs (siRNAs), which are liberated from double-stranded (ds)RNA precursors by Dicer and guide the RNA-induced silencing complex (RISC) to targets. Although principles governing small RNA sorting into RISC have been uncovered, the spectrum of RNA species that can be targeted by Dicer proteins, particularly the viral RNAs present during an infection, are poorly understood. Dicer-2 potently restricts viral infection in insects by generating virus-derived siRNAs from viral RNA. To better characterize the substrates of Dicer-2, we examined the virus-derived siRNAs produced during the Drosophila antiviral RNAi response to four different viruses using high-throughput sequencing. We found that each virus was uniquely targeted by the RNAi pathway; dicing substrates included dsRNA replication intermediates and intramolecular RNA stem loops. For instance, a putative intergenic RNA hairpin encoded by Rift Valley Fever virus generates abundant small RNAs in both Drosophila and mosquito cells, while repetitive sequences within the genomic termini of Vaccinia virus, which give rise to abundant small RNAs in Drosophila, were found to be transcribed in both insect and mammalian cells. Moreover, we provide evidence that the RNA species targeted by Dicer-2 can be modulated by the presence of a viral suppressor of RNAi. This study uncovered several novel, heavily targeted features within viral genomes, offering insight into viral replication, viral immune evasion strategies, and the mechanism of antiviral RNAi. PMID:23424633

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

    PubMed

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

    2014-07-01

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

  12. Multiple Infections of Rodents with Zoonotic Pathogens in Austria

    PubMed Central

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

    2014-01-01

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

  13. Filamentous pathogen effector functions: of pathogens, hosts and microbiomes.

    PubMed

    Rovenich, Hanna; Boshoven, Jordi C; Thomma, Bart P H J

    2014-08-01

    Microorganisms play essential roles in almost every environment on earth. For instance, microbes decompose organic material, or establish symbiotic relationships that range from pathogenic to mutualistic. Symbiotic relationships have been particularly well studied for microbial plant pathogens and have emphasized the role of effectors; secreted molecules that support host colonization. Most effectors characterized thus far play roles in deregulation of host immunity. Arguably, however, pathogens not only deal with immune responses during host colonization, but also encounter other microbes including competitors, (myco)parasites and even potential co-operators. Thus, part of the effector catalog may target microbiome co-inhabitants rather than host physiology. PMID:24879450

  14. Synthetic Protocells Interact with Viral Nanomachinery and Inactivate Pathogenic Human Virus

    PubMed Central

    Moscona, Anne; LaVan, David A.

    2011-01-01

    We present a new antiviral strategy and research tool that could be applied to a wide range of enveloped viruses that infect human beings via membrane fusion. We test this strategy on two emerging zoonotic henipaviruses that cause fatal encephalitis in humans, Nipah (NiV) and Hendra (HeV) viruses. In the new approach, artificial cell-like particles (protocells) presenting membrane receptors in a biomimetic manner were developed and found to attract and inactivate henipavirus envelope glycoprotein pseudovirus particles, preventing infection. The protocells do not accumulate virus during the inactivation process. The use of protocells that interact with, but do not accumulate, viruses may provide significant advantages over current antiviral drugs, and this general approach may have wide potential for antiviral development. PMID:21390296

  15. Viral pathogens and the advantage of sex in the perennial grass Anthoxanthum odoratum

    Microsoft Academic Search

    STEVEN E. KELLEY

    SUMMARY The ubiquity of sexual reproduction among plants and animals remains one of the major unresolved paradoxes of modern evolutionary biology. In order for sex to be maintained in populations, sex must confer immediate and substantial fitness benefits. Theoreticians have proposed numerous mechanisms to explain how such advantages arise, but experimental data are few. In one well-studied population of the

  16. Viral Pathogens and the Advantage of Sex in the Perennial Grass Anthoxanthum odoratum

    Microsoft Academic Search

    Steven E. Kelley

    1994-01-01

    The ubiquity of sexual reproduction among plants and animals remains one of the major unresolved paradoxes of modern evolutionary biology. In order for sex to be maintained in populations, sex must confer immediate and substantial fitness benefits. Theoreticians have proposed numerous mechanisms to explain how such advantages arise, but experimental data are few. In one well-studied population of the perennial

  17. Antibodies to Selected Viral and Bacterial Pathogens in European Wild Boars from Southcentral Spain

    Microsoft Academic Search

    Joaquin Vicente; Luis Leon-Vizcaino; Christian Gortazar; Maria JoseCubero; Monica Gonzalez

    Serum samples from 78 European wild boars (Sus scrofa) harvested during the 1999-2000 hunting season were tested for an- tibodies to Brucella spp., classical swine fever virus, Erysipelothrix rhusiopathiae, Haemophi- lus parasuis, Leptospira interrogans serovar po- mona, Mycoplasma hyopneumoniae, pseudo- rabies virus (PRV), porcine parvovirus (PPV), porcine reproductive and respiratory syndrome virus, Salmonella serogroups B, C, and D, Streptococcus suis,

  18. Antibodies to bovine bacterial and viral pathogens in pronghorns in Alberta, 1983.

    PubMed

    Kingscote, B F; Bohac, J G

    1986-10-01

    Sera from 210 pronghorns (Antilocapra americana) ranging in southeastern Alberta were tested for antibodies to disease agents present in indigenous cattle. No antibodies to Brucella abortus, Leptospira interrogans serovars pomona, hardjo, or grippotyphosa, or infectious bovine rhinotracheitis virus were found. Antibodies at prevalences of 43.8% and 49.2% were detected to bovine virus diarrhea (BVD) and parainfluenza type 3 (PI-3) viruses, respectively. The much higher prevalence of BVD virus antibodies in cattle than in pronghorns, and the occurrence of clinical bovine PI-3 infection in the study area, suggest that cattle may be a source of infection to the pronghorns. PMID:2845155

  19. ANTIBODIES TO BOVINE BACTERIAL AND VIRAL PATHOGENS IN PRONGHORNS IN ALBERTA, 1983

    Microsoft Academic Search

    B. F. Kingscote; J. G. Bohac

    Sera from 210 pronghorns (Antilocapra americana) ranging in southeastern Alberta were tested for antibodies to disease agents present in indigenous cattle. No antibodies to Brucella abort us, Leptospira interrogans serovars pomona, hardjo, or grippotyphosa, or infectious bovine rhinotracheitis virus were found. Antibodies at prevalences of 43.8% and 49.2% were detected to bovine virus diarrhea (BVD) and parainfluenza type 3 (P1-3)

  20. [Canine parvovirus: recent knowledge of the origin and development of a viral pathogen].

    PubMed

    Truyen, U

    1994-12-01

    Canine parvovirus (CPV) is a "new" virus that suddenly emerged in the mid 1970s. Antigenetically it is very similar to the long known feline panleukopenia virus (FPV). Soon after its appearance CPV was classified as a mutant of FPV. As with all "new" viruses, CPV continues to show active evolution, obvious by the appearance of new antigenic types. Interestingly, the new types, designated CPV-2a and CPV-2b, completely replaced the original type. This review summarizes the facts that are known about the emergence and evolution of CPV and discusses the relevance of the new antigenic types for the diagnosis of CPV and the vaccination against it. PMID:7716757

  1. Prevalence of viral pathogens WSSV and IHHNV in wild organisms at the Pacific Coast of Mexico.

    PubMed

    Macías-Rodríguez, Norma A; Mañón-Ríos, Nathalie; Romero-Romero, Jesús L; Camacho-Beltrán, Erika; Magallanes-Tapia, Marco A; Leyva-López, Norma E; Hernández-López, Jorge; Magallón-Barajas, Francisco J; Perez-Enriquez, Ricardo; Sánchez-González, Sergio; Méndez-Lozano, Jesús

    2014-02-01

    This study investigated whether white spot syndrome virus and Infectious hypodermal and hematopoietic necrosis virus, can survive in wild invertebrates and vertebrates in the environment surrounding shrimp farms along the Pacific coast of Mexico. The evidences imply that both viruses have a potential of persisting in crabs, blue, white and brown shrimps. The most prevalent virus, IHHNV was present in 19.5% (344/1736) followed by WSSV in 3.6% (65/1736). Coinfection of WSSV and IHHNV was also detected in crabs, blue and white shrimps. This is the first prevalence report of WSSV and IHHNV associated with wildlife species in Mexico. PMID:24300441

  2. [Pathogenicity of noncytophatic isolates of bovine viral diarrhea virus in experimentally infected seronegative calves].

    PubMed

    Glotov, A G; Glotova, T I; Za?tsev, Iu N; P'iankov, O V; Sergeev, A N; Guliukin, M I

    2014-01-01

    The results of experimental infection of seronegative calves with three non-cytopathogenic (NCP) isolates of BVDV isolated from cattle with different clinical manifestations of the disease belonging to genotype 1 (subgenotype 1a, 1b and 1d) are presented. All tested isolates showed the virulence for seronegative calves 4 to 6 months of age. Belonging to biotype did not correlate with the ability of the virus to infect the lymphoid tissues and to induce leukopenia. All isolates of the virus led to "transiting" leukopenia (up to 2880-3800 kl/mm3) for 8-10 days after infection. Isolate cluster 1d was more virulent and caused the development of a mild respiratory syndrome and short-term diarrhea. The virulence was "strain-dependent". PMID:25549468

  3. Kinetics of UV254 inactivation of selected viral pathogens in a static system

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to ascertain baseline inactivation constants for Influenza Type A, PRRSV, BVDV, and Reovirus at varying UV254 dosages. Viruses in culture medium were exposed to 9 different dosages of UV254. Following exposure, the viruses were harvested, stored at -80 C and titrated ...

  4. Exposure Control Plan Bloodborne Pathogen Program

    E-print Network

    Natelson, Douglas

    Exposure Control Plan Bloodborne Pathogen Program 1. Introduction 2. Occupational Exposure Bloodborne Pathogen Program 1. INTRODUCTION OSHA defines occupational exposure as reasonably anticipated skin set forth in the Bloodborne Pathogens (BBP) Standard are necessary to provide protection to employees

  5. 40 CFR 503.32 - Pathogens.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...enteric viruses in the sewage sludge after pathogen treatment is less than one...for the pathogen treatment process, the sewage sludge continues to be Class...helminth ova in the sewage sludge after pathogen treatment is less than...

  6. Lethal mutagenesis failure may augment viral adaptation.

    PubMed

    Paff, Matthew L; Stolte, Steven P; Bull, James J

    2014-01-01

    Lethal mutagenesis, the attempt to extinguish a population by elevating its mutation rate, has been endorsed in the virology literature as a promising approach for treating viral infections. In support of the concept, in vitro studies have forced viral extinction with high doses of mutagenic drugs. However, the one known mutagenic drug used on patients commonly fails to cure infections, and in vitro studies typically find a wide range of mutagenic conditions permissive for viral growth. A key question becomes how subsequent evolution is affected if the viral population is mutated but avoids extinction--Is viral adaptation augmented rather than suppressed? Here we consider the evolution of highly mutated populations surviving mutagenesis, using the DNA phage T7. In assays using inhibitory hosts, whenever resistance mutants were observed, the mutagenized populations exhibited higher frequencies, but some inhibitors blocked plaque formation by even the mutagenized stock. Second, outgrowth of previously mutagenized populations led to rapid and potentially complete fitness recovery but polymorphism was slow to decay, and mutations exhibited inconsistent patterns of change. Third, the combination of population bottlenecks with mutagenesis did cause fitness declines, revealing a vulnerability that was not apparent from mutagenesis of large populations. The results show that a population surviving high mutagenesis may exhibit enhanced adaptation in some environments and experience little negative fitness consequences in many others. PMID:24092771

  7. Lethal Mutagenesis Failure May Augment Viral Adaptation

    PubMed Central

    Paff, Matthew L.; Stolte, Steven P.; Bull, James J.

    2014-01-01

    Lethal mutagenesis, the attempt to extinguish a population by elevating its mutation rate, has been endorsed in the virology literature as a promising approach for treating viral infections. In support of the concept, in vitro studies have forced viral extinction with high doses of mutagenic drugs. However, the one known mutagenic drug used on patients commonly fails to cure infections, and in vitro studies typically find a wide range of mutagenic conditions permissive for viral growth. A key question becomes how subsequent evolution is affected if the viral population is mutated but avoids extinction—Is viral adaptation augmented rather than suppressed? Here we consider the evolution of highly mutated populations surviving mutagenesis, using the DNA phage T7. In assays using inhibitory hosts, whenever resistance mutants were observed, the mutagenized populations exhibited higher frequencies, but some inhibitors blocked plaque formation by even the mutagenized stock. Second, outgrowth of previously mutagenized populations led to rapid and potentially complete fitness recovery but polymorphism was slow to decay, and mutations exhibited inconsistent patterns of change. Third, the combination of population bottlenecks with mutagenesis did cause fitness declines, revealing a vulnerability that was not apparent from mutagenesis of large populations. The results show that a population surviving high mutagenesis may exhibit enhanced adaptation in some environments and experience little negative fitness consequences in many others. PMID:24092771

  8. Pathogenic obesity and nutraceuticals.

    PubMed

    Conroy, K P; Davidson, I M; Warnock, M

    2011-11-01

    Over a decade of intense research in the field of obesity has led to the knowledge that chronic, excessive adipose tissue expansion leads to an increase in the risk for CVD, type 2 diabetes mellitus and cancer. This is primarily thought to stem from the low-grade, systemic inflammatory response syndrome that characterises adipose tissue in obesity, and this itself is thought to arise from the complex interplay of factors including metabolic endotoxaemia, increased plasma NEFA, hypertrophic adipocytes and localised hypoxia. Plasma concentrations of vitamins and antioxidants are lower in obese individuals than in the non-obese, which is hypothesised to negatively affect the development of inflammation and disease in obesity. This paper provides a review of the current literature investigating the potential of nutraceuticals to ameliorate the development of oxidative stress and inflammation in obesity, thereby limiting the onset of obesity complications. Research has found nutraceuticals able to positively modulate the activity of adipocyte cell lines and further positive effects have been found in other aspects of pathogenic obesity. While their ability to affect weight loss is still controversial, it is clear that they have a great potential to reverse the development of overweight and obesity-related comorbidities; this, however, still requires much research especially that utilising well-structured randomised controlled trials. PMID:21854698

  9. Interferon Regulatory Factor-1 Protects from Fatal Neurotropic Infection with Vesicular Stomatitis Virus by Specific Inhibition of Viral Replication in Neurons

    PubMed Central

    Nair, Sharmila; Michaelsen-Preusse, Kristin; Finsterbusch, Katja; Stegemann-Koniszewski, Sabine; Bruder, Dunja; Grashoff, Martina; Korte, Martin; Köster, Mario; Kalinke, Ulrich; Hauser, Hansjörg; Kröger, Andrea

    2014-01-01

    The innate immune system protects cells against invading viral pathogens by the auto- and paracrine action of type I interferon (IFN). In addition, the interferon regulatory factor (IRF)-1 can induce alternative intrinsic antiviral responses. Although both, type I IFN and IRF-1 mediate their antiviral action by inducing overlapping subsets of IFN stimulated genes, the functional role of this alternative antiviral action of IRF-1 in context of viral infections in vivo remains unknown. Here, we report that IRF-1 is essential to counteract the neuropathology of vesicular stomatitis virus (VSV). IFN- and IRF-1-dependent antiviral responses act sequentially to create a layered antiviral protection program against VSV infections. Upon intranasal infection, VSV is cleared in the presence or absence of IRF-1 in peripheral organs, but IRF-1?/? mice continue to propagate the virus in the brain and succumb. Although rapid IFN induction leads to a decline in VSV titers early on, viral replication is re-enforced in the brains of IRF-1?/? mice. While IFN provides short-term protection, IRF-1 is induced with delayed kinetics and controls viral replication at later stages of infection. IRF-1 has no influence on viral entry but inhibits viral replication in neurons and viral spread through the CNS, which leads to fatal inflammatory responses in the CNS. These data support a temporal, non-redundant antiviral function of type I IFN and IRF-1, the latter playing a crucial role in late time points of VSV infection in the brain. PMID:24675692

  10. [Central nervous system viral infections--analysis of routine laboratory results].

    PubMed

    Siennicka, Joanna; Trzci?ska, Agnieszka

    2008-01-01

    The most of registered in Poland cases of encephalitis and meningitis have viral aetiology. Confirmation of viral central nervous system (CNS) infection and diagnosis of pathogenic agent is critical for therapeutic treatment, especially if antiviral chemotherapy is available. The aim of this work was analysis of routine laboratory results obtained in Laboratory of Department of Virology NIZP-PZH by examination of materials obtained from 82 medical canters in Poland in aim of CNS infection confirmation. Materials, cerebrospinal fluid (CSN) n=277, and CSN together with serum (n=452) were obtained from patients aged from 3 days to 83 years. Accordingly with the range of tests performed in Laboratory of Department of Virology NIZP-PZH, obtained samples were examinated for 11 viral infections: HSV, CMV, EBV, VZV, HHV-6, HHV-7, TBE, measles, mumps, rubella and enteroviruses. Confirmation of viral infection was obtained in 104 out of 729 tested patients (14.3%). The highest number of confirmations was obtained in case of TBE infection (18.4%) and HSV (9.2%). The methods gave the highest number of confirmations were testing of intrathecal IgG synthesis (14.4%) and presence of IgM in serum (10.3%). If test was conducted only with CSF, confirmation of viral infection was obtained in 13 cases (4.7%). In conclusions it was ascertained that testing CSF and serum samples together greatly increase possibility of etiological agent detection and a range of ordered tests (i.e. intrathecal synthesis versus PCR) should account dynamics of pathological process. PMID:19143179

  11. Bacterial and viral etiology of childhood diarrhea in Ouagadougou, Burkina Faso

    PubMed Central

    2013-01-01

    Background Diarrhea is the most frequent health problem among children in developing countries. This study investigated the bacterial and viral etiology and related clinical and epidemiological factors in children with acute diarrhea in Ouagadougou, Burkina Faso. Methods Stool specimens were collected from 283 children under 5 years of age visiting hospital due to acute diarrhea and from 60 healthy controls of similar age. Pathogens were investigated by using conventional culture techniques, PCR and immunochromatographic testing. Salmonella and Shigella strains were serotyped and their susceptibility to 23 antimicrobial agents was determined by the agar dilution method. Results At least one pathogen was detected in 64% of the 283 patients and in 8% of the 60 controls (p?pathogens were found in 11% of the patients and in 2% of the controls (p?=?0.028). Viruses were found mainly in children of???2 years of age, whereas bacteria were equally prevalent among all the age groups. Viral infections occurred mostly during the cool dry season and the bacterial infections during the rainy season. Fever (64%) and vomiting (61%) were the most common symptoms associated with diarrhea. Only one Salmonella strain was resistant to nalidixic acid and ciprofloxacin. Of the Shigella strains, one was resistant to nalidixic acid but 81% to trimethoprim- sulfamethoxazole, 63% to streptomycin and 50% to ampicillin. Most of all the other Salmonella and Shigella strains were sensitive to all antimicrobials tested. Conclusion Rotaviruses and diarrheal E. coli were the most predominant pathogens associated with acute diarrhea in Burkinabe children. Constant antimicrobial surveillance is warranted to observe for the emergence of enteric bacteria resistant to antimicrobials that are important in treatment also of severe infections. PMID:23506294

  12. Opportunistic Premise Plumbing Pathogens: Increasingly Important Pathogens in Drinking Water.

    PubMed

    Falkinham, Joseph O; Pruden, Amy; Edwards, Marc

    2015-01-01

    Opportunistic premise plumbing pathogens are responsible for a significant number of infections whose origin has been traced to drinking water. These opportunistic pathogens represent an emerging water borne disease problem with a major economic cost of at least $1 billion annually. The common features of this group of waterborne pathogens include: disinfectant-resistance, pipe surface adherence and biofilm formation, growth in amoebae, growth on low organic concentrations, and growth at low oxygen levels. Their emergence is due to the fact that conditions resulting from drinking water treatment select for them. As such, there is a need for novel approaches to reduce exposure to these pathogens. In addition to much-needed research, controls to reduce numbers and human exposure can be instituted independently by utilities and homeowners and hospital- and building-operators. PMID:26066311

  13. Opportunistic Premise Plumbing Pathogens: Increasingly Important Pathogens in Drinking Water

    PubMed Central

    Falkinham, Joseph O.; Pruden, Amy; Edwards, Marc

    2015-01-01

    Opportunistic premise plumbing pathogens are responsible for a significant number of infections whose origin has been traced to drinking water. These opportunistic pathogens represent an emerging water borne disease problem with a major economic cost of at least $1 billion annually. The common features of this group of waterborne pathogens include: disinfectant-resistance, pipe surface adherence and biofilm formation, growth in amoebae, growth on low organic concentrations, and growth at low oxygen levels. Their emergence is due to the fact that conditions resulting from drinking water treatment select for them. As such, there is a need for novel approaches to reduce exposure to these pathogens. In addition to much-needed research, controls to reduce numbers and human exposure can be instituted independently by utilities and homeowners and hospital- and building-operators. PMID:26066311

  14. Inducible nitric oxide synthase expression in chronic viral hepatitis. Evidence for a virus-induced gene upregulation.

    PubMed Central

    Majano, P L; García-Monzón, C; López-Cabrera, M; Lara-Pezzi, E; Fernández-Ruiz, E; García-Iglesias, C; Borque, M J; Moreno-Otero, R

    1998-01-01

    Increased nitric oxide (NO) production may contribute to the pathological changes featuring in some inflammatory diseases, but the role of NO in chronic viral hepatitis is still unknown. We compared the inducible NO synthase (NOS2) expression in the liver of patients with chronic viral hepatitis with that of both nonviral liver disease and histologically normal liver. NOS2 expression was assessed by immunohistochemical and in situ hybridization studies of liver biopsy sections. An intense hepatocellular NOS2 reactivity was detected in chronic viral hepatitis, whereas it was weakly or not observed in nonviral liver disease or normal liver, respectively. In addition, we determined whether the hepatitis B virus (HBV) might regulate the synthesis of this enzyme. NOS2 mRNA and protein levels as well as enzyme activity were assessed in cytokine-stimulated HBV-transfected and untransfected hepatoma cells. Transfection with either HBV genome or HBV X gene resulted in induction of NOS2 mRNA expression, and the maximal induction of this transcript and NO production was observed in cytokine-stimulated HBV-transfected cells. These results indicate that hepatotropic viral infections are able to upregulate the NOS2 gene expression in human hepatocytes, suggesting that NO may mediate important pathogenic events in the course of chronic viral hepatitis. PMID:9525976

  15. Host Pathogen Relations: Exploring Animal Models for Fungal Pathogens

    PubMed Central

    Harwood, Catherine G.; Rao, Reeta P.

    2014-01-01

    Pathogenic fungi cause superficial infections but pose a significant public health risk when infections spread to deeper tissues, such as the lung. Within the last three decades, fungi have been identified as the leading cause of nosocomial infections making them the focus of research. This review outlines the model systems such as the mouse, zebrafish larvae, flies, and nematodes, as well as ex vivo and in vitro systems available to study common fungal pathogens. PMID:25438011

  16. [Epidemiology of viral hepatitis in Mexico].

    PubMed

    Panduro, Arturo; Escobedo Meléndez, Griselda; Fierro, Nora A; Ruiz Madrigal, Bertha; Zepeda-Carrillo, Eloy Alfonso; Román, Sonia

    2011-01-01

    The main etiology of liver disease in Mexico is alcohol and viral hepatitis. The aim of the present study was to analyze the current epidemiology of viral hepatitis in Mexico. From 2000 to 2007 the Ministry of Health reported 192 588 cases of hepatitis, 79% HAV, 3.3% HBV, 6% HCV, and 12% without a specific etiologic factor. Due to high endemic areas for HBV infection in native Mexican population, limitations in the diagnostic sensitivity and specificity of the serological immunoassays used to date and presence of occult hepatitis B in the country, the real prevalence of HBV infection could be even higher than HCV in Mexico. Hepatitis E virus in cirrhotic patients and in porcine farms could at least partially explain the cases of hepatitis that are diagnosed without a specific etiologic agent. Specific strategies to establish control regulations against viral hepatitis infections in Mexico are proposed. PMID:21877071

  17. Controlling viral capsid assembly with templating

    NASA Astrophysics Data System (ADS)

    Hagan, Michael F.

    2008-05-01

    We develop coarse-grained models that describe the dynamic encapsidation of functionalized nanoparticles by viral capsid proteins. We find that some forms of cooperative interactions between protein subunits and nanoparticles can dramatically enhance rates and robustness of assembly, as compared to the spontaneous assembly of subunits into empty capsids. For large core-subunit interactions, subunits adsorb onto core surfaces en masse in a disordered manner, and then undergo a cooperative rearrangement into an ordered capsid structure. These assembly pathways are unlike any identified for empty capsid formation. Our models can be directly applied to recent experiments in which viral capsid proteins assemble around functionalized inorganic nanoparticles [Sun , Proc. Natl. Acad. Sci. U.S.A. 104, 1354 (2007)]. In addition, we discuss broader implications for understanding the dynamic encapsidation of single-stranded genomic molecules during viral replication and for developing multicomponent nanostructured materials.

  18. HUMAN VIRAL ONCOGENESIS: A CANCER HALLMARKS ANALYSIS

    PubMed Central

    Mesri, Enrique A.; Feitelson, Mark; Munger, Karl

    2014-01-01

    Approximately twelve percent of all human cancers are caused by oncoviruses. Human viral oncogenesis is complex and only a small percentage of the infected individuals develop cancer and often many years to decades after initial infection. This reflects the multistep nature of viral oncogenesis, host genetic variability and the fact that viruses contribute to only a portion of the oncogenic events. In this review, the Hallmarks of Cancer framework of Hanahan & Weinberg (2000 and 2011) is used to dissect the viral, host and environmental co-factors that contribute to the biology of multistep oncogenesis mediated by established human oncoviruses. The viruses discussed include Epstein Barr Virus (EBV), high-risk Human Papillomaviruses (HPV16/18), Hepatitis B and C viruses (HBV, HCV respectively), Human T-cell lymphotropic virus-1 (HTLV-1) and Kaposi’s sarcoma herpesvirus (KSHV). PMID:24629334

  19. Viral croup: diagnosis and a treatment algorithm.

    PubMed

    Petrocheilou, Argyri; Tanou, Kalliopi; Kalampouka, Efthimia; Malakasioti, Georgia; Giannios, Christos; Kaditis, Athanasios G

    2014-05-01

    Viral croup is a frequent disease in early childhood. Although it is usually self-limited, it may occasionally become life-threatening. Mild croup is characterized by the presence of stridor without intercostal retractions, whereas moderate-to-severe croup is accompanied by increased work of breathing. A single dose of orally administered dexamethasone (0.15-0.6?mg/kg) is the mainstay of treatment with addition of nebulized epinephrine only in cases of moderate-to-severe croup. Nebulized budesonide (2?mg) can be given alternatively to children who do not tolerate oral dexamethasone. Exposure to cold air or administration of cool mist are treatment interventions for viral croup that are not supported by published evidence, but breathing heliox can potentially reduce the work of breathing related to upper airway obstruction. In summary, corticosteroids may decrease the intensity of viral croup symptoms irrespective to their severity on presentation to the emergency department. PMID:24596395

  20. IFITM Proteins Restrict Viral Membrane Hemifusion

    PubMed Central

    Golfetto, Ottavia; Bungart, Brittani; Li, Minghua; Ding, Shilei; He, Yuxian; Liang, Chen; Lee, James C.; Gratton, Enrico; Cohen, Fredric S.; Liu, Shan-Lu

    2013-01-01

    The interferon-inducible transmembrane (IFITM) protein family represents a new class of cellular restriction factors that block early stages of viral replication; the underlying mechanism is currently not known. Here we provide evidence that IFITM proteins restrict membrane fusion induced by representatives of all three classes of viral membrane fusion proteins. IFITM1 profoundly suppressed syncytia formation and cell-cell fusion induced by almost all viral fusion proteins examined; IFITM2 and IFITM3 also strongly inhibited their fusion, with efficiency somewhat dependent on cell types. Furthermore, treatment of cells with IFN also markedly inhibited viral membrane fusion and entry. By using the Jaagsiekte sheep retrovirus envelope and influenza A virus hemagglutinin as models for study, we showed that IFITM-mediated restriction on membrane fusion is not at the steps of receptor- and/or low pH-mediated triggering; instead, the creation of hemifusion was essentially blocked by IFITMs. Chlorpromazine (CPZ), a chemical known to promote the transition from hemifusion to full fusion, was unable to rescue the IFITM-mediated restriction on fusion. In contrast, oleic acid (OA), a lipid analog that generates negative spontaneous curvature and thereby promotes hemifusion, virtually overcame the restriction. To explore the possible effect of IFITM proteins on membrane molecular order and fluidity, we performed fluorescence labeling with Laurdan, in conjunction with two-photon laser scanning and fluorescence-lifetime imaging microscopy (FLIM). We observed that the generalized polarizations (GPs) and fluorescence lifetimes of cell membranes expressing IFITM proteins were greatly enhanced, indicating higher molecularly ordered and less fluidized membranes. Collectively, our data demonstrated that IFITM proteins suppress viral membrane fusion before the creation of hemifusion, and suggested that they may do so by reducing membrane fluidity and conferring a positive spontaneous curvature in the outer leaflets of cell membranes. Our study provides novel insight into the understanding of how IFITM protein family restricts viral membrane fusion and infection. PMID:23358889

  1. Metatranscriptomic analysis of extremely halophilic viral communities.

    PubMed

    Santos, Fernando; Moreno-Paz, Mercedes; Meseguer, Inmaculada; López, Cristina; Rosselló-Mora, Ramon; Parro, Víctor; Antón, Josefa

    2011-10-01

    Hypersaline environments harbour the highest number of viruses reported for aquatic environments. In crystallizer ponds from solar salterns, haloviruses coexist with extremely halophilic Archaea and Bacteria and present a high diversity although little is known about their activity. In this work, we analyzed the viral expression in one crystallizer using a metatranscriptomic approach in which clones from a metaviromic library were immobilized in a microarray and used as probes against total mRNA extracted from the hypersaline community. This approach has two advantages: (i) it overcomes the fact that there is no straightforward, unambiguous way to extract viral mRNA from bulk mRNAs and (ii) it makes the sequencing of all mRNAs unnecessary. Transcriptomic data indicated that the halovirus assemblage was highly active at the time of sampling and the viral groups with the highest expression levels were those related to high GC content haloarchaea and Salinibacter representatives, which are minor components in the environment. Moreover, the changes in the viral expression pattern and in the numbers of free viral particles were analyzed after submitting the samples to two stress conditions: ultraviolet-radiation and dilution. Results showed that Archaea were more sensitive than Bacteria to these stress conditions. The overexpression in the predicted archaeal virus fraction raised and the total numbers of free viruses increased. Furthermore, we identified some very closely related viral clones, displaying single-nucleotide polymorphisms, which were expressed only under certain conditions. These clones could be part of very closely related virus genomes for which we propose the term 'ecoviriotypes'. PMID:21490689

  2. Viral Serine/Threonine Protein Kinases ?

    PubMed Central

    Jacob, Thary; Van den Broeke, Céline; Favoreel, Herman W.

    2011-01-01

    Phosphorylation represents one the most abundant and important posttranslational modifications of proteins, including viral proteins. Virus-encoded serine/threonine protein kinases appear to be a feature that is unique to large DNA viruses. Although the importance of these kinases for virus replication in cell culture is variable, they invariably play important roles in virus virulence. The current review provides an overview of the different viral serine/threonine protein kinases of several large DNA viruses and discusses their function, importance, and potential as antiviral drug targets. PMID:21084474

  3. Recognition of pathogens by plants

    E-print Network

    Holt III, Ben F.

    and respond to specific pathogens? Unlike animals, plants do not have the luxury of a circulating immune and localized programmed cell death. The hypersensitive response serves to Magazine R5 Figure 1 The interaction

  4. Lectins in human pathogenic fungi.

    PubMed

    Gallegos, Belém; Martínez, Ruth; Pérez, Laura; Del Socorro Pina, María; Perez, Eduardo; Hernández, Pedro

    2014-01-01

    Lectins are carbohydrate-binding proteins widely distributed in nature. They constitute a highly diverse group of proteins consisting of many different protein families that are, in general, structurally unrelated. In the last few years, mushroom and other fungal lectins have attracted wide attention due to their antitumour, antiproliferative and immunomodulatory activities. The present mini-review provides concise information about recent developments in understanding lectins from human pathogenic fungi. A bibliographic search was performed in the Science Direct and PubMed databases, using the following keywords "lectin", "fungi", "human" and "pathogenic". Lectins present in fungi have been classified; however, the role played by lectins derived from human pathogenic fungi in infectious processes remains uncertain; thus, this is a scientific field requiring more research. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). PMID:24270074

  5. Immune responses of Helicoverpa armigera to different kinds of pathogens

    PubMed Central

    2010-01-01

    Background Insects react against pathogens through innate immunity. The cotton bollworm Helicoverpa armigera (H. armigera) is an important defoliator and an extremely destructive pest insect of many crops. The elucidation of the mechanism of the immune response of H. armigera to various pathogens can provide a theoretical basis for new approaches to biologically control this pest. Results Four kinds of pathogens Bacillus thuringiensis, Klebsiella pneumoniae, Candida albicans, and Autographa californica multiple nucleocapsid nucleopolyhedrovirus harbored green fluorescence protein and polyhedron (AcMNPV-GFP) were used to challenge the insect. The cellular and humoral immune responses to the pathogens were analyzed in the challenged H. armigera. The results show that in the five kinds of haemocytes, only granulocytes phagocytized the Gram-negative and Gram-positive bacteria and fungi. All haemocytes can be infected by AcMNPV. Fourteen immune-related genes including pattern recognition receptors (PRRs) such as peptidoglycan recognition proteins (HaPGRP and HaPGRP C) and Gram-Negative Bacteria-Binding Protein (HaGNBP), and antimicrobial peptides (AMPs) such as cecropin-1, 2 and 3 (HaCec-1, 2 and 3), lysozyme (HaLys), attacin (HaAtt), gallerimycin-like (HaGall), gloverin-like (HaGlo), moricin-like (HaMor), cobatoxin-like (HaCob), galiomicin-like (HaGali), and immune inducible protein (HaIip) appeared in different expression profiles to different pathogen infections. The transcripts of 13 immune related genes (except HaPGRPC) are obviously up-regulated by Gram-positive bacteria. HaCec-1 and 3, HaMor, HaAtt, HaLys, HaIip, HaPGRP and HaGNBP are greatly up-regulated after fungal infection. HaGNBP, HaCec-2, HaGall, HaGlo, HaMor, HaCob, HaGali obviously increased in Gram-negative bacterial infection. Only five genes, HaGNBP, HaCec-1, HaGali, HaGlo, and HaLys, are weakly up-regulated after viral infection. The AMP transcripts had higher expression levels than the PRR transcripts after the microbial challenge. Conclusions These data suggest that the granulocytes are the major phagocytes in H. armigera. All haemocytes can be infected by AcMNPV. The transcripts of 14 immune related genes have different expression patterns in H. armigera infected by different pathogens, which means that the immune-related genes may have different functions against various kinds of pathogens. PMID:20196874

  6. NLR functions beyond pathogen recognition

    Microsoft Academic Search

    Thomas A Kufer; Philippe J Sansonetti

    2011-01-01

    The last 10 years have witnessed the identification of a new class of intracellular pattern-recognition molecules—the nucleotide-binding domain and leucine-rich repeat–containing family (NLR). Members of this family garnered interest as pattern-recognition receptors able to trigger inflammatory responses against pathogens. Many studies support a pathogen-recognition function for human NLR proteins and shed light on their role in the broader control of

  7. Viral degradasome hijacks mitochondria to suppress innate immunity.

    PubMed

    Goswami, Ramansu; Majumdar, Tanmay; Dhar, Jayeeta; Chattopadhyay, Saurabh; Bandyopadhyay, Sudip K; Verbovetskaya, Valentina; Sen, Ganes C; Barik, Sailen

    2013-08-01

    The balance between the innate immunity of the host and the ability of a pathogen to evade it strongly influences pathogenesis and virulence. The two nonstructural (NS) proteins, NS1 and NS2, of respiratory syncytial virus (RSV) are critically required for RSV virulence. Together, they strongly suppress the type I interferon (IFN)-mediated innate immunity of the host cells by degrading or inhibiting multiple cellular factors required for either IFN induction or response pathways, including RIG-I, IRF3, IRF7, TBK1 and STAT2. Here, we provide evidence for the existence of a large and heterogeneous degradative complex assembled by the NS proteins, which we named "NS-degradasome" (NSD). The NSD is roughly ?300-750 kD in size, and its degradative activity was enhanced by the addition of purified mitochondria in vitro. Inside the cell, the majority of the NS proteins and the substrates of the NSD translocated to the mitochondria upon RSV infection. Genetic and pharmacological evidence shows that optimal suppression of innate immunity requires mitochondrial MAVS and mitochondrial motility. Together, we propose a novel paradigm in which the mitochondria, known to be important for the innate immune activation of the host, are also important for viral suppression of the innate immunity. PMID:23877405

  8. Viral receptor-binding site antibodies with diverse germline origins.

    PubMed

    Schmidt, Aaron G; Therkelsen, Matthew D; Stewart, Shaun; Kepler, Thomas B; Liao, Hua-Xin; Moody, M Anthony; Haynes, Barton F; Harrison, Stephen C

    2015-05-21

    Vaccines for rapidly evolving pathogens will confer lasting immunity if they elicit antibodies recognizing conserved epitopes, such as a receptor-binding site (RBS). From characteristics of an influenza-virus RBS-directed antibody, we devised a signature motif to search for similar antibodies. We identified, from three vaccinees, over 100 candidates encoded by 11 different VH genes. Crystal structures show that antibodies in this class engage the hemagglutinin RBS and mimic binding of the receptor, sialic acid, by supplying a critical dipeptide on their projecting, heavy-chain third complementarity determining region. They share contacts with conserved, receptor-binding residues but contact different residues on the RBS periphery, limiting the likelihood of viral escape when several such antibodies are present. These data show that related modes of RBS recognition can arise from different germline origins and mature through diverse affinity maturation pathways. Immunogens focused on an RBS-directed response will thus have a broad range of B cell targets. PMID:25959776

  9. Waterborne pathogens in urban watersheds.

    PubMed

    Arnone, Russell D; Walling, Joyce Perdek

    2007-03-01

    A serious concern for managers of water resources, pathogens in the urban environment easily enter waters through a number of pathways, including discharge of inadequately treated sewage, stormwater runoff, combined sewer overflows and sanitary sewer overflows. Pathogens in US ambient water bodies are regulated under the Clean Water Act (CWA), while pathogens in drinking water supplies are regulated under the Safe Drinking Water Act. Total maximum daily loads (TMDLs) are developed in accordance with CWA regulations for ambient water bodies with bacterial concentrations exceeding the water quality standard, which generally is a measure of a bacterial indicator organism. However, developing a TMDL for a supplementary indicator or pathogen is also required if a use impairment would still exist even after the water body is in compliance with the standard. This occurs because indicator organisms do not reflect the presence of pathogen contamination with complete certainty. The evaluation of pathogen indicators and summary of epidemiological studies presented are resources for those developing TMDLs to achieve water quality standards and restore water bodies to their intended uses. PMID:17402286

  10. Distinct macrophage subpopulations regulate viral encephalitis but not viral clearance in the CNS.

    PubMed

    Steel, Christina D; Kim, Woong-Ki; Sanford, Larry D; Wellman, Laurie L; Burnett, Sandra; Van Rooijen, Nico; Ciavarra, Richard P

    2010-09-14

    Intranasal application of vesicular stomatitis virus (VSV) induces acute encephalitis characterized by a pronounced myeloid and T cell infiltrate. The role of distinct phagocytic populations on VSV encephalitis was therefore examined in this study. Ablation of peripheral macrophages did not impair VSV encephalitis or viral clearance from the brain, whereas, depletion of splenic marginal dendritic cells impaired this response and enhanced morbidity/mortality. Selective depletion of brain perivascular macrophages also suppressed this response without altering viral clearance. Thus, two anatomically distinct phagocytic populations regulate VSV encephalitis in a non-redundant fashion although neither population is essential for viral clearance in the CNS. PMID:20599280

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

    USGS Publications Warehouse

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

    2008-01-01

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

  12. A Novel Role of the Potyviral Helper Component Proteinase Contributes To Enhance the Yield of Viral Particles

    PubMed Central

    Gallo, Araíz; Calvo, María; Pérez, José de Jesús

    2014-01-01

    ABSTRACT The helper component proteinase (HCPro) is an indispensable, multifunctional protein of members of the genus Potyvirus and other viruses of the family Potyviridae. This viral factor is directly involved in diverse steps of viral infection, such as aphid transmission, polyprotein processing, and suppression of host antiviral RNA silencing. In this paper, we show that although a chimeric virus based on the potyvirus Plum pox virus lacking HCPro, which was replaced by a heterologous silencing suppressor, caused an efficient infection in Nicotiana benthamiana plants, its viral progeny had very reduced infectivity. Making use of different approaches, here, we provide direct evidence of a previously unknown function of HCPro in which the viral factor enhances the stability of its cognate capsid protein (CP), positively affecting the yield of virions and consequently improving the infectivity of the viral progeny. Site-directed mutagenesis revealed that the ability of HCPro to stabilize CP and enhance the yield of infectious viral particles is not linked to any of its previously known activities and helped us to delimit the region of HCPro involved in this function in the central region of the protein. Moreover, the function is highly specific and cannot be fulfilled by the HCPro of a heterologous potyvirus. The importance of this novel requirement in regulating the sorting of the viral genome to be subjected to replication, translation, and encapsidation, thus contributing to the synchronization of these viral processes, is discussed. IMPORTANCE Potyviruses form one of the most numerous groups of plant viruses and are a major cause of crop loss worldwide. It is well known that these pathogens make use of virus-derived multitasking proteins, as well as dedicated host factors, to successfully infect their hosts. Here, we describe a novel requirement for the proper yield and infectivity of potyviral progeny. In this case, such a function is performed by the extensively studied viral factor HCPro, which seems to use an unknown mechanism that is not linked to its previously described activities. To our knowledge, this is the first time that a factor different from capsid protein (CP) has been shown to be directly involved in the yield of potyviral particles. Based on the data presented here, we hypothesize that this capacity of HCPro might be involved in the coordination of mutually exclusive activities of the viral genome by controlling correct assembly of CP in stable virions. PMID:24942578

  13. Memory CD4+ T cells induce innate responses independent of pathogen

    PubMed Central

    Strutt, Tara M.; McKinstry, K. Kai; Dibble, John P.; Winchell, Caylin; Kuang, Yi; Curtis, Jonathan D.; Huston, Gail; Dutton, Richard W.; Swain, Susan L.

    2010-01-01

    Inflammation induced by recognition of pathogen-associated molecular patterns dramatically impacts subsequent adaptive responses. We asked if the adaptive immune system can also affect the character and magnitude of innate inflammatory responses. We find that the response of memory, but not naïve, CD4+ T cells enhances production of multiple innate inflammatory cytokines and chemokines (IIC) in the lung, and that during influenza infection, this leads to early control of virus. Memory CD4+ T cell induced IIC and viral control require cognate antigen recognition and are optimal when memory cells are either T helper type 1 (TH1)- or TH17-polarized, but are independent of interferon-? (IFN-?) and tumor necrosis factor-? (TNF-?) production and do not require activation of conserved pathogen recognition pathways. This represents a novel mechanism by which memory CD4+ T cells induce an early innate response that enhances immune protection against pathogens. PMID:20436484

  14. Thinking globally, acting locally: harnessing the immune system to deal with recalcitrant pathogens.

    PubMed

    Russell, Michael W

    2015-01-01

    Traditional approaches to harnessing the immune system to confront infectious diseases depend on vaccines, which have generally proven highly effective, but for many infections these either are not available or are of limited effectiveness. Although antibiotic therapy has been extremely successful in reducing the burden of bacterial disease, the emergence of resistance among several important pathogens threatens to undermine this accomplishment, and despite some successes chemotherapeutic treatments for viral, fungal, and parasitic infections are more limited. Understanding the mechanisms whereby pathogens manipulate the immune system to favor their survival, or exploit weaknesses in host immunity, can lead to novel approaches for the treatment of infections by redirecting host immune responses against the pathogen. Such treatments may be most effectively applied at the mucosal locations which are frequently the sites of initial infection and may also suggest new approaches for vaccine development. PMID:25922391

  15. Thinking Globally, Acting Locally: Harnessing the Immune System to Deal with Recalcitrant Pathogens

    PubMed Central

    2015-01-01

    ABSTRACT Traditional approaches to harnessing the immune system to confront infectious diseases depend on vaccines, which have generally proven highly effective, but for many infections these either are not available or are of limited effectiveness. Although antibiotic therapy has been extremely successful in reducing the burden of bacterial disease, the emergence of resistance among several important pathogens threatens to undermine this accomplishment, and despite some successes chemotherapeutic treatments for viral, fungal, and parasitic infections are more limited. Understanding the mechanisms whereby pathogens manipulate the immune system to favor their survival, or exploit weaknesses in host immunity, can lead to novel approaches for the treatment of infections by redirecting host immune responses against the pathogen. Such treatments may be most effectively applied at the mucosal locations which are frequently the sites of initial infection and may also suggest new approaches for vaccine development. PMID:25922391

  16. Viral infection induces dependence of neuronal M2 muscarinic receptors on cyclooxygenase in guinea pig lung.

    PubMed Central

    Kahn, R M; Okanlami, O A; Jacoby, D B; Fryer, A D

    1996-01-01

    Inhibitory M2 muscarinic receptors on parasympathetic nerve endings in the lungs decrease release of acetylcholine, inhibiting vagally induced bronchoconstriction. Neuronal M2 receptor function can be studied using selective agonists and antagonists such as pilocarpine and gallamine. In pathogen-free guinea pigs indomethacin (1 mg/kg) did not alter the effect of either gallamine or pilocarpine, thus in pathogen free animals neuronal M2 muscarinic receptors function independently of cyclooxygenase products. However, in guinea pigs infected with virus, (which causes temporary loss of M2 receptor function), and then allowed to recover for 8 wk (to allow recovery of M2 receptors), indomethacin prevented both gallamine's potentiation and pilocarpine's inhibition of vagally induced bronchoconstriction. This new effect of indomethacin was not blocked by the addition of a 5-lipoxygenase inhibitor, AA861. However, the selective COX II inhibitor, L-745,337, had the same effect as indomethacin. Since exposure to ozone also caused neuronal M2 receptors to become dependent upon cyclooxygenase the effects of viral infection are likely to be due to inflammation. Thus, despite apparent recovery of normal M2 receptor function after viral infection or ozone, linkage of these receptors is chronically altered such that they become largely dependent on the activity of COX II. PMID:8755638

  17. Occult Viral Hepatitis and Noncirrhotic Hepatocellular Carcinoma

    Microsoft Academic Search

    Stuart C. Gordon

    2005-01-01

    The achievement of a sustained virologic response to hepatitis C antiviral therapy represents a milestone occurrence that many tout as a cure. Recent studies, however, have found trace HCV viral material both among sustained responders and in patients with chronic liver disease who are HCV RNA negative, suggesting the entity of occult hepatitis C. As a body of literature emerges

  18. Bovine Viral Diarrhea Virus: Global Status

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite the success of regional bovine viral diarrhea viruses (BVDV) eradication programs, infections with this diverse group of viruses remain a source of economic loss for producers worldwide. There is a wide range of variation among BVDV results in differences in genotype (BVDV1 and BVDV2), biot...

  19. 65 FR 56807 - Equine Viral Arteritis

    Federal Register 2010, 2011, 2012, 2013, 2014

    2000-09-20

    ...viral disease characterized by fever, edema, conjunctivitis...principal means of the spread of infection among horses that are closely...significant role in maintaining EVA infection in horse populations. When...vaccination against the disease or infection with the EVA virus, can...

  20. STUDIES OF WATERBORNE AGENTS OF VIRAL GASTROENTERITIS

    EPA Science Inventory

    The etiologic agent of a large outbreak of waterborne viral gastroenteritis was detected employing immune electron microscopy (IEM) and a newly developed solid phase radioimmunoassay (RIA). This agent, referred to as the Snow Mountain Agent (SMA), is 27-32 nm. in diameter, has cu...