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1

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

PubMed Central

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

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

2013-01-01

2

Evidence for Multiple Recent Host Species Shifts among the Ranaviruses (Family Iridoviridae)? †  

PubMed Central

Members of the genus Ranavirus (family Iridoviridae) have been recognized as major viral pathogens of cold-blooded vertebrates. Ranaviruses have been associated with amphibians, fish, and reptiles. At this time, the relationships between ranavirus species are still unclear. Previous studies suggested that ranaviruses from salamanders are more closely related to ranaviruses from fish than they are to ranaviruses from other amphibians, such as frogs. Therefore, to gain a better understanding of the relationships among ranavirus isolates, the genome of epizootic hematopoietic necrosis virus (EHNV), an Australian fish pathogen, was sequenced. Our findings suggest that the ancestral ranavirus was a fish virus and that several recent host shifts have taken place, with subsequent speciation of viruses in their new hosts. The data suggesting several recent host shifts among ranavirus species increase concern that these pathogens of cold-blooded vertebrates may have the capacity to cross numerous poikilothermic species barriers and the potential to cause devastating disease in their new hosts. PMID:20042506

Jancovich, James K.; Bremont, Michel; Touchman, Jeffrey W.; Jacobs, Bertram L.

2010-01-01

3

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

PubMed Central

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

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

2012-01-01

4

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

PubMed Central

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

Grayfer, Leon; De Jesús Andino, Francisco

2014-01-01

5

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

PubMed

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

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

2014-08-11

6

Persistence of an amphibian ranavirus in aquatic communities.  

PubMed

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

Johnson, A F; Brunner, J L

2014-09-30

7

Ecopathology of Ranaviruses Infecting Amphibians  

PubMed Central

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

Miller, Debra; Gray, Matthew; Storfer, Andrew

2011-01-01

8

Ranavirus outbreaks in amphibian populations of northern Idaho  

USGS Publications Warehouse

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).

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

2011-01-01

9

Virion-associated viral proteins of a Chinese giant salamander (Andrias davidianus) iridovirus (genus Ranavirus) and functional study of the major capsid protein (MCP).  

PubMed

Chinese giant salamander iridovirus (CGSIV) is the emerging causative agent to farmed Chinese giant salamanders in nationwide China. CGSIV is a member of the common midwife toad ranavirus (CMTV) subset of the amphibian-like ranavirus (ALRV) in the genus Ranavirus of Iridoviridae family. However, viral protein information on ALRV is lacking. In this first proteomic analysis of ALRV, 40 CGSIV viral proteins were detected from purified virus particles by liquid chromatography-tandem mass spectrometry analysis. The transcription products of all 40 identified virion proteins were confirmed by reverse transcription polymerase chain reaction analysis. Temporal expression pattern analysis combined with drug inhibition assay indicated that 37 transcripts of the 40 virion protein genes could be classified into three temporal kinetic classes, namely, 5 immediate early, 12 delayed early, and 20 late genes. The presence of major capsid proteins (MCP, ORF019L) and a proliferating cell nuclear antigen (ORF025L) was further confirmed by Western blot analysis. The functions of MCP were also determined by small interfering RNA (siRNA)-based knockdown assay and anti-recombinant MCP serum-based neutralization testing. At low dosages of CGSIV, siRNA-based knockdown of the MCP gene effectively inhibited CGSIV replication in fathead minnow cells. The antiviral effect observed in the anti-MCP serum-based neutralization test confirms the crucial function of the MCP gene in CGSIV replication. Taken together, detailed information on the virion-associated viral proteins of ALRV is presented for the first time. Our results also provide evidence that MCP is essential for CGSIV replication in vitro. PMID:24906872

Li, Wei; Zhang, Xin; Weng, Shaoping; Zhao, Gaoxiang; He, Jianguo; Dong, Chuanfu

2014-08-01

10

Transmission of Ranavirus between Ectothermic Vertebrate Hosts  

PubMed Central

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

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

2014-01-01

11

Influence of Dendritic Cells on Viral Pathogenicity  

Microsoft Academic Search

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.

Giulia Freer; Donatella Matteucci

2009-01-01

12

Ranaviruses: Cold Blooded Killers!  

E-print Network

) 34% (12%, 23%) #12;2 History of Ranavirus Die-offs First Isolated: ·Dr. Allan Granoff ·Rana pipiens Norman Wells, NWT >30 States & 20 Spp; 4 Provinces Ambystomatidae Salamandridae Uncommon Lithobates

Gray, Matthew

13

Matthew J. Gray Ranaviruses  

E-print Network

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

Gray, Matthew

14

Influence of Dendritic Cells on Viral Pathogenicity  

PubMed Central

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. Certain viruses are able to skew cytokine secretion by DCs inducing and/or downregulating the immune system with the aim of facilitating and prolonging release of progeny. Thus, the interaction of DCs with viruses most often results in the absence of disease or complete recovery when natural functions of DCs prevail, but may lead to chronic illness or death when these functions are outmanoeuvred by viruses in the exploitation of DCs. PMID:19649323

Freer, Giulia; Matteucci, Donatella

2009-01-01

15

Molecular constraints to interspecies transmission of viral pathogens  

Microsoft Academic Search

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

Richard Webby; Erich Hoffmann; Robert Webster

2004-01-01

16

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

PubMed

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

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

2009-02-25

17

Richness and Composition of Niche-Assembled Viral Pathogen Communities  

PubMed Central

The pathogen and parasite community that inhabits every free-living organism can control host vital rates including lifespan and reproductive output. To date, however, there have been few experiments examining pathogen community assembly replicated at large-enough spatial scales to inform our understanding of pathogen dynamics in natural systems. Pathogen community assembly may be driven by neutral stochastic colonization and extinction events or by niche differentiation that constrains pathogen distributions to particular environmental conditions, hosts, or vectors. Here, we present results from a regionally-replicated experiment investigating the community of barley and cereal yellow dwarf viruses (B/CYDV's) in over 5000 experimentally planted individuals of six grass species along a 700 km latitudinal gradient along the Pacific coast of North America (USA) in response to experimentally manipulated nitrogen and phosphorus supplies. The composition of the virus community varied predictably among hosts and across nutrient-addition treatments, indicating niche differentiation among virus species. There were some concordant responses among the viral species. For example, the prevalence of most viral species increased consistently with perennial grass cover, leading to a 60% increase in the richness of the viral community within individual hosts (i.e., coinfection) in perennial-dominated plots. Furthermore, infection rates of the six host species in the field were highly correlated with vector preferences assessed in laboratory trials. Our results reveal the importance of niche differentiation in structuring virus assemblages. Virus species distributions reflected a combination of local host community composition, host species-specific vector preferences, and virus responses to host nutrition. In addition, our results suggest that heterogeneity among host species in their capacity to attract vectors or support pathogens between growing seasons can lead to positive covariation among virus species. PMID:23468848

Seabloom, Eric W.; Borer, Elizabeth T.; Lacroix, Christelle; Mitchell, Charles E.; Power, Alison G.

2013-01-01

18

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

PubMed

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

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

2010-11-01

19

Cellular immune responses against viral pathogens in shrimp.  

PubMed

Shrimp is one of the most important commercial marine species worldwide; however, viral diseases threaten the healthy development of shrimp aquaculture. In order to develop efficient control strategies against viral diseases, researchers have begun focusing increasing attention to the molecular mechanism of shrimp innate immunity. Although knowledge of shrimp humoral immunity has grown significantly in recent years, very little information is available about the cell-mediated immune responses. Several cellular processes such as phagocytosis, apoptosis, and RNA interference critical in cellular immune response play a significant role in endogenous antiviral activity in shrimp. In this review, we summarize the emerging research and highlight key mediators of cellular immune response to viral pathogens. PMID:25111591

Xu, Dandan; Liu, Weifeng; Alvarez, Angel; Huang, Tianzhi

2014-12-01

20

Point detection of bacterial and viral pathogens using oral samples  

NASA Astrophysics Data System (ADS)

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

Malamud, Daniel

2008-04-01

21

Immunohistochemical staining for ranaviruses Introduction: Ranaviruses negatively impact amphibian populations  

E-print Network

(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

Gray, Matthew

22

High susceptibility of the endangered dusky gopher frog to ranavirus.  

PubMed

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

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

2014-11-14

23

Infection and co-infection by the amphibian chytrid fungus and ranavirus in wild Costa Rican frogs.  

PubMed

Amphibian populations are globally threatened by emerging infectious diseases, and 2 pathogens in particular are recognized as major threats: the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) and ranaviruses. Here, we evaluated the prevalence of infection by Bd and ranavirus in an assemblage of frogs from a lowland wet forest in Costa Rica. We found an overall prevalence of 21.3% for Bd and 16.6% for ranavirus, and detected both pathogens widely among our 20 sampled species. We found a positive association between ranavirus and Bd infection in one of our 4 most commonly sampled species. We also found a positive but non-significant association between infection by ranavirus and infection by Bd among species overall. Our study is among the first detailed evaluations of ranavirus prevalence in the American tropics, and to our knowledge is the first to detect a positive association between Bd and ranavirus in any species. Considerable research attention has focused on the ecology of Bd in tropical regions, yet we argue that greater research focus is necessary to understand the ecology and conservation impact of ranaviruses on amphibian populations already decimated by the emergence of Bd. PMID:23709470

Whitfield, Steven M; Geerdes, Erica; Chacon, Iria; Ballestero Rodriguez, Erick; Jimenez, Randall R; Donnelly, Maureen A; Kerby, Jacob L

2013-05-27

24

Ranavirus: past, present and future  

PubMed Central

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

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

25

Quantitation of ranaviruses in cell culture and tissue samples.  

PubMed

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

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

2011-01-01

26

Amphibian ranavirus transmission and persistence  

E-print Network

Amphibian ranavirus transmission and persistence Jesse Brunner With an emphasis on ecological & Owens 2002 " ATV Brunner et al. 2005 " FV3 Pearman et al. 2004, Hoverman et al. 2010, Warne et al or Cophixalus ornatus adults (Cullen & Owen 2002) #12;Routes of transmission: direct contact Brunner et al

Gray, Matthew

27

Mass mortality associated with a frog virus 3-like Ranavirus infection in farmed tadpoles Rana catesbeiana from Brazil  

PubMed Central

Ranviruses (Iridoviridae) are increasingly associated with mortality events in amphibians, fish, and reptiles. They have been recently associated with mass mortality events in Brazilian farmed tadpoles of the American bullfrog Rana catesbeiana Shaw. 1802. The objectives of the present study were to further characterize the virus isolated from sick R. catesbeiana tadpoles and confirm the etiology in these outbreaks. Sick tadpoles were collected in 3 farms located in Goiás State, Brazil, from 2003 to 2005 and processed for virus isolation and characterization, microbiology, histopathology, and parasitology. The phylogenetic relationships of Rana catesbeiana ranavirus (RCV-BR) with other genus members was investigated by PCR with primers specific for the major capsid protein gene (MCP) and the RNA polymerase DNA-dependent gene (Pol II). Sequence analysis and multiple alignments for MCP products showed >99% amino acid identity with other ranaviruses, while Pol II products showed 100% identity. Further diagnostics of the pathology including histology and transmission electron microscopy confirmed the viral etiology of these mass deaths. As for as we know, this is the first report of a ranaviral infection affecting aquatic organisms in Brazil. Additionally, our results suggest that American bullfrogs may have served as a vector of transmission of this virus, which highlights the potential threat of amphibian translocation in the world distribution of pathogens. PMID:20066953

Mazzoni, Rolando; de Mesquita, Albenones Jose; Fleury, Luiz Fernando F.; de Brito, Wilia Marta Elsner Diederichsen; Nunes, Iolanda A.; Robert, Jacques; Morales, Heidi; Coelho, Alexandre Siqueira Guedes; Barthasson, Denise Leao; Galli, Leonardo; Catroxo, Marcia H. B.

2010-01-01

28

Ranavirus in Chelonians of North America  

E-print Network

Freeranging survey · Blanding's (58) and painted turtles (47) in Illi iIllinois · 0% PCR prevalence · Gopher Overview · Introduction/Background · Diagnosis of Ranavirus · Prevalence of Ranavirus in eastern box turtles · Pathogenesis/Transmission · Therapeutics #12;7/16/2011 2 Obj ti 1Objective 1 Introduction

Gray, Matthew

29

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

PubMed Central

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

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

2014-01-01

30

First evidence of amphibian chytrid fungus (Batrachochytrium dendrobatidis) and ranavirus in Hong Kong amphibian trade.  

PubMed

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

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

2014-01-01

31

New approaches to the inhibition of replication of viral pathogens.  

PubMed

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

Kumar, Anil; Silverstein, Peter S

2011-11-01

32

Differential Host Response, Rather Than Early Viral Replication Efficiency, Correlates with Pathogenicity Caused by Influenza Viruses  

PubMed Central

Influenza viruses exhibit large, strain-dependent differences in pathogenicity in mammalian hosts. Although the characteristics of severe disease, including uncontrolled viral replication, infection of the lower airway, and highly inflammatory cytokine responses have been extensively documented, the specific virulence mechanisms that distinguish highly pathogenic strains remain elusive. In this study, we focused on the early events in influenza infection, measuring the growth rate of three strains of varying pathogenicity in the mouse airway epithelium and simultaneously examining the global host transcriptional response over the first 24 hours. Although all strains replicated equally rapidly over the first viral life-cycle, their growth rates in both lung and tracheal tissue strongly diverged at later times, resulting in nearly 10-fold differences in viral load by 24 hours following infection. We identified separate networks of genes in both the lung and tracheal tissues whose rapid up-regulation at early time points by specific strains correlated with a reduced viral replication rate of those strains. The set of early-induced genes in the lung that led to viral growth restriction is enriched for both NF-?B binding site motifs and members of the TREM1 and IL-17 signaling pathways, suggesting that rapid, NF-?B –mediated activation of these pathways may contribute to control of viral replication. Because influenza infection extending into the lung generally results in severe disease, early activation of these pathways may be one factor distinguishing high- and low-pathogenicity strains. PMID:24073225

Askovich, Peter S.; Sanders, Catherine J.; Rosenberger, Carrie M.; Diercks, Alan H.; Dash, Pradyot; Navarro, Garnet; Vogel, Peter; Doherty, Peter C.; Thomas, Paul G.; Aderem, Alan

2013-01-01

33

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

PubMed

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

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

34

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

PubMed

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

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

2012-05-15

35

Amphibian commerce and the threat of pathogen  

E-print Network

(pathogen pollution) · Possible implications of wildlife trade ­ Declines and extinctions ­ Disruption of historical relationshipsrelationships · 1.48 billion live animals imported by US since 2000 ­ 92 amphibians ­ Worldwide amphibian declines and extinctions · RV Ranaviruses· RV Ranaviruses ­ Affect

Gray, Matthew

36

Challenges in environmental detection of human viral pathogens.  

PubMed

There is substantial potential for human exposure to viruses in environmental matrixes. Identification of virally contaminated environmental reservoirs requires assays with sufficient sensitivity to detect low copy numbers of viral targets. However, low detection sensitivity frequently requires sample concentration during which inhibitors to downstream assays co-isolate with desired target. Conventional detection assays (e.g., cell culture, polymerase chain reaction) require a priori selection of appropriate cell lines or primers and probes based on the viruses anticipated to be present in the sample. This can underestimate exposure risks by excluding unidentified or unknown virus. Emerging methods including nonspecific adsorption/elution, filtration, and total nucleic acid sequencing, that are capable of concentrating, purifying, and detecting total virus and/or total virus nucleic acid will aid in estimates of exposure risk, source tracking, intervention efficacy, and evaluation of virus fate and transport. Development and implementation of novel virus detection techniques must integrate quality assurance guidelines to validate results and provide opportunities for interstudy comparison. PMID:22440969

Julian, Timothy R; Schwab, Kellogg J

2012-02-01

37

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

PubMed

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

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

2014-06-01

38

Unbiased parallel detection of viral pathogens in clinical samples by use of a metagenomic approach.  

PubMed

Viral infectious diseases represent a major threat to public health and are among the greatest disease burdens worldwide. Rapid and accurate identification of viral agents is crucial for both outbreak control and estimating regional disease burdens. Recently developed metagenomic methods have proven to be powerful tools for simultaneous pathogen detection. Here, we performed a systematic study of the capability of the short-read-based metagenomic approach in the molecular detection of viral pathogens in nasopharyngeal aspirate samples from patients with acute lower respiratory tract infections (n = 16). Using the high-throughput capacity of ultradeep sequencing and a dedicated data interpretation method, we successfully identified seven species of known respiratory viral agents from 15 samples, a result that was consistent with results of conventional PCR assays. We also detected a coinfected case that was missed by regular PCR testing. Using the metagenomic data, 11 draft genomes of the abundantly detected viruses in the samples were reconstructed with 21.84% to 98.53% coverage. Our results show the power of the short-read-based metagenomic approach for accurate and parallel screening of viral pathogens. Although there are some inherent difficulties in applying this approach to clinical samples, including a lack of controls, limited specimen quantity, and high contamination rate, our work will facilitate further application of this unprecedented high-throughput method to clinical samples. PMID:21813714

Yang, Jian; Yang, Fan; Ren, Lili; Xiong, Zhaohui; Wu, Zhiqiang; Dong, Jie; Sun, Lilian; Zhang, Ting; Hu, Yongfeng; Du, Jiang; Wang, Jianwei; Jin, Qi

2011-10-01

39

Rapid Accurate Identification of Bacterial and Viral Pathogens  

SciTech Connect

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

Dunn, John

2007-03-09

40

Viral Metagenome Analysis to Guide Human Pathogen Monitoring in Environmental Samples  

PubMed Central

Aims The aim of this study was to develop and demonstrate an approach for describing the diversity of human pathogenic viruses in an environmentally isolated viral metagenome. Methods and Results In silico bioinformatic experiments were used to select an optimum annotation strategy for discovering human viruses in virome datasets, and applied to annotate a class B biosolids virome. Results from the in silico study indicated that less than 1% errors in virus identification could be achieved when nucleotide-based search programs (BLASTn or tBLASTx), viral genome only databases, and sequence reads greater than 200 nt were considered. Within the 51,925 annotated sequences, 94 DNA and 19 RNA sequences were identified as human viruses. Virus diversity included environmentally transmitted agents such as parechovirus, coronavirus, adenovirus, and aichi virus, as well as viruses associated with chronic human infections such as human herpes and hepatitis C viruses. Conclusions This study provided a bioinformatic approach for identifying pathogens in a virome dataset, and demonstrated the human virus diversity in a relevant environmental sample. Significance and Impact of Study As the costs of next generation sequencing decrease, the pathogen diversity described by virus metagenomes will provide an unbiased guide for subsequent cell-culture and quantitative pathogen analyses, and ensures that highly enriched and relevant pathogens are not neglected in exposure and risk assessments. PMID:21272046

Bibby, Kyle; Viau, Emily; Peccia, Jordan

2011-01-01

41

Human ecology in pathogenic landscapes: two hypotheses on how land use change drives viral emergence  

PubMed Central

The emergence of novel viral diseases is driven by socioeconomic, demographic and environmental changes. These include land use changes such as deforestation, agricultural expansion and habitat degradation. However, the links between land use change and disease emergence are poorly understood and likely complex. In this review, we propose two hypotheses for the mechanisms by which land use change can lead to viral emergence: 1) by perturbing disease dynamics in multi-host disease systems via impacts on cross-species transmission rates (the ‘perturbation’ hypothesis); and 2) by allowing exposure of novel hosts to a rich pool of pathogen diversity (the ‘pathogen pool’ hypothesis). We discuss ways that these two hypotheses might be tested using a combination of ecological and virological approaches, and how this may provide novel control and prevention strategies. PMID:23415415

Murray, Kris. A.; Daszak, Peter

2013-01-01

42

Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination  

PubMed Central

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

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

2014-01-01

43

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

PubMed

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

Alum, Absar; Rock, Channah; Abbaszadegan, Morteza

2014-01-01

44

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

PubMed Central

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

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

2006-01-01

45

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

PubMed

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

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

1998-07-01

46

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

PubMed

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

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

2010-07-01

47

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

PubMed Central

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

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

2011-01-01

48

Role of Interferon Antagonist Activity of Rabies Virus Phosphoprotein in Viral Pathogenicity?  

PubMed Central

The fixed rabies virus (RV) strain Nishigahara kills adult mice after intracerebral inoculation, whereas the chicken embryo fibroblast cell-adapted strain Ni-CE causes nonlethal infection in adult mice. We previously reported that the chimeric CE(NiP) strain, which has the phosphoprotein (P protein) gene from the Nishigahara strain in the genetic background of the Ni-CE strain, causes lethal infection in adult mice, indicating that the P gene is responsible for the different pathogenicities of the Nishigahara and Ni-CE strains. Previous studies demonstrated that RV P protein binds to the interferon (IFN)-activated transcription factor STAT1 and blocks IFN signaling by preventing its translocation to the nucleus. In this study, we examine the molecular mechanism by which RV P protein determines viral pathogenicity by comparing the IFN antagonist activities of the Nishigahara and Ni-CE P proteins. The results, obtained from both RV-infected cells and cells transfected to express P protein only, show that Ni-CE P protein is significantly impaired for its capacity to block IFN-activated STAT1 nuclear translocation and, consequently, inhibits IFN signaling less efficiently than Nishigahara P protein. Further, it was demonstrated that a defect in the nuclear export of Ni-CE P protein correlates with a defect in its ability to cause the mislocalization of STAT1. These data provide the first evidence that the capacity of the RV P protein to inhibit STAT1 nuclear translocation and IFN signaling correlates with the viral pathogenicity. PMID:20427527

Ito, Naoto; Moseley, Gregory W.; Blondel, Danielle; Shimizu, Kenta; Rowe, Caitlin L.; Ito, Yuki; Masatani, Tatsunori; Nakagawa, Keisuke; Jans, David A.; Sugiyama, Makoto

2010-01-01

49

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

PubMed Central

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

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

50

Magnitude of the US trade in amphibians and presence of Batrachochytrium dendrobatidis and ranavirus infection in imported North American bullfrogs ( Rana catesbeiana)  

Microsoft Academic Search

Amphibians are globally threatened by anthropogenic habitat loss, the wildlife trade and emerging diseases. Previous authors have hypothesized that the spread of the amphibian disease chytridiomycosis (Batrachochytrium dendrobatidis) and amphibian ranaviruses are associated with the international trade in live amphibians. The North American bullfrog (Rana catesbeiana) is thought to be a carrier of these pathogens, is globally traded as a

Lisa M. Schloegel; Angela M. Picco; A. Marm Kilpatrick; Angela J. Davies; Alex D. Hyatt; Peter Daszak

2009-01-01

51

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

PubMed Central

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

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

2014-01-01

52

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

PubMed Central

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

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

2009-01-01

53

Endogenous MMTV Proviruses Induce Susceptibility to Both Viral and Bacterial Pathogens  

PubMed Central

Most inbred mice carry germline proviruses of the retrovirus, mouse mammary tumor virus (MMTV) (called Mtvs), which have multiple replication defects. A BALB/c congenic mouse strain lacking all endogenous Mtvs (Mtv-null) was resistant to MMTV oral and intraperitoneal infection and tumorigenesis compared to wild-type BALB/c mice. Infection of Mtv-null mice with an MMTV-related retrovirus, type B leukemogenic virus, also resulted in severely reduced viral loads and failure to induce T-cell lymphomas, indicating that resistance is not dependent on expression of a superantigen (Sag) encoded by exogenous MMTV. Resistance to MMTV in Mtv-null animals was not due to neutralizing antibodies. Further, Mtv-null mice were resistant to rapid mortality induced by intragastric inoculation of the Gram-negative bacterium, Vibrio cholerae, but susceptibility to Salmonella typhimurium was not significantly different from BALB/c mice. Susceptibility to both MMTV and V. cholerae was reconstituted by the presence of any one of three endogenous Mtvs located on different chromosomes and was associated with increased pathogen load. One of these endogenous proviruses is known to encode only Sag. Therefore, Mtv-encoded Sag appears to provide a unique genetic susceptibility to specific viruses and bacteria. Since human endogenous retroviruses also encode Sags, these studies have broad implications for pathogen-induced responses in mice and humans. PMID:17140288

Bhadra, Sanchita; Lozano, Mary M; Payne, Shelley M; Dudley, Jaquelin P

2006-01-01

54

PREVALENCE OF RANAVIRUS IN GREEN FROGS (Lithobates clamitans) ACROSS INDIANA  

E-print Network

habitat and a mul]-stage life cycle, amphibians have an increased suscepPREVALENCE OF RANAVIRUS IN GREEN FROGS (Lithobates clamitans) ACROSS INDIANA, Jennings, Posey, Whitley Coun]es), targe]ng green frog (Lithobates clamitans) tadpoles

Gray, Matthew

55

Amphibian ranaviruses in Canada historical, current and future research  

E-print Network

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

Gray, Matthew

56

Genes controlling vaccine responses and disease resistance to respiratory viral pathogens in cattle  

PubMed Central

Farm animals remain at risk of endemic, exotic and newly emerging viruses. Vaccination is often promoted as the best possible solution, and yet for many pathogens, either there are no appropriate vaccines or those that are available are far from ideal. A complementary approach to disease control may be to identify genes and chromosomal regions that underlie genetic variation in disease resistance and response to vaccination. However, identification of the causal polymorphisms is not straightforward as it generally requires large numbers of animals with linked phenotypes and genotypes. Investigation of genes underlying complex traits such as resistance or response to viral pathogens requires several genetic approaches including candidate genes deduced from knowledge about the cellular pathways leading to protection or pathology, or unbiased whole genome scans using markers spread across the genome. Evidence for host genetic variation exists for a number of viral diseases in cattle including bovine respiratory disease and anecdotally, foot and mouth disease virus (FMDV). We immunised and vaccinated a cattle cross herd with a 40-mer peptide derived from FMDV and a vaccine against bovine respiratory syncytial virus (BRSV). Genetic variation has been quantified. A candidate gene approach has grouped high and low antibody and T cell responders by common motifs in the peptide binding pockets of the bovine major histocompatibility complex (BoLA) DRB3 gene. This suggests that vaccines with a minimal number of epitopes that are recognised by most cattle could be designed. Whole genome scans using microsatellite and single nucleotide polymorphism (SNP) markers has revealed many novel quantitative trait loci (QTL) and SNP markers controlling both humoral and cell-mediated immunity, some of which are in genes of known immunological relevance including the toll-like receptors (TLRs). The sequencing, assembly and annotation of livestock genomes and is continuing apace. In addition, provision of high-density SNP chips should make it possible to link phenotypes with genotypes in field populations without the need for structured populations or pedigree information. This will hopefully enable fine mapping of QTL and ultimate identification of the causal gene(s). The research could lead to selection of animals that are more resistant to disease and new ways to improve vaccine efficacy. PMID:21621277

Glass, Elizabeth J.; Baxter, Rebecca; Leach, Richard J.; Jann, Oliver C.

2012-01-01

57

Genes controlling vaccine responses and disease resistance to respiratory viral pathogens in cattle.  

PubMed

Farm animals remain at risk of endemic, exotic and newly emerging viruses. Vaccination is often promoted as the best possible solution, and yet for many pathogens, either there are no appropriate vaccines or those that are available are far from ideal. A complementary approach to disease control may be to identify genes and chromosomal regions that underlie genetic variation in disease resistance and response to vaccination. However, identification of the causal polymorphisms is not straightforward as it generally requires large numbers of animals with linked phenotypes and genotypes. Investigation of genes underlying complex traits such as resistance or response to viral pathogens requires several genetic approaches including candidate genes deduced from knowledge about the cellular pathways leading to protection or pathology, or unbiased whole genome scans using markers spread across the genome. Evidence for host genetic variation exists for a number of viral diseases in cattle including bovine respiratory disease and anecdotally, foot and mouth disease virus (FMDV). We immunised and vaccinated a cattle cross herd with a 40-mer peptide derived from FMDV and a vaccine against bovine respiratory syncytial virus (BRSV). Genetic variation has been quantified. A candidate gene approach has grouped high and low antibody and T cell responders by common motifs in the peptide binding pockets of the bovine major histocompatibility complex (BoLA) DRB3 gene. This suggests that vaccines with a minimal number of epitopes that are recognised by most cattle could be designed. Whole genome scans using microsatellite and single nucleotide polymorphism (SNP) markers has revealed many novel quantitative trait loci (QTL) and SNP markers controlling both humoral and cell-mediated immunity, some of which are in genes of known immunological relevance including the toll-like receptors (TLRs). The sequencing, assembly and annotation of livestock genomes and is continuing apace. In addition, provision of high-density SNP chips should make it possible to link phenotypes with genotypes in field populations without the need for structured populations or pedigree information. This will hopefully enable fine mapping of QTL and ultimate identification of the causal gene(s). The research could lead to selection of animals that are more resistant to disease and new ways to improve vaccine efficacy. PMID:21621277

Glass, Elizabeth J; Baxter, Rebecca; Leach, Richard J; Jann, Oliver C

2012-07-15

58

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

PubMed

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

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

2013-11-12

59

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

PubMed Central

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

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

2013-01-01

60

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

PubMed

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

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

2012-10-01

61

Interactions between viral and prokaryotic pathogens in a mixed infection with cardiovirus and mycoplasma.  

PubMed

In the natural environment, animal and plant viruses often share ecological niches with microorganisms, but the interactions between these pathogens, although potentially having important implications, are poorly investigated. The present report demonstrates, in a model system, profound mutual effects of mycoplasma and cardioviruses in animal cell cultures. In contrast to mycoplasma-free cells, cultures contaminated with Mycoplasma hyorhinis responded to infection with encephalomyocarditis virus (EMCV), a picornavirus, but not with poliovirus (also a picornavirus), with a strong activation of a DNase(s), as evidenced by the TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) immunofluorescence assay and electrophoretic analysis of host DNA. This degradation was reminiscent of that observed upon apoptosis but was caspase independent, judging by the failure of the specific pan-caspase inhibitor Q-VD-OPh to prevent it. The electrophoretic mobility of the enzyme responsible for DNA degradation and dependence of its activity on ionic conditions strongly suggested that it was represented by a DNase(s) of mycoplasma origin. In cells not infected with EMCV, the relevant DNase was dormant. The possibility is discussed that activation of the mycoplasma DNase might be linked to a relatively early increase in permeability of plasma membrane of the infected cells caused by EMCV. This type of unanticipated virus-mycoplasma "cooperation" may exemplify the complexity of pathogen-host interactions under conditions when viruses and microorganisms are infecting the same host. In the course of the present study, it was also demonstrated that pan-caspase inhibitor zVAD(OMe).fmk strongly suppressed cardiovirus polyprotein processing, illustrating an additional pitfall in investigations of viral effects on the apoptotic system of host cells. PMID:19605479

Lidsky, Peter V; Romanova, Lyudmila I; Kolesnikova, Marina S; Bardina, Maryana V; Khitrina, Elena V; Hato, Stanleyson V; van Kuppeveld, Frank J M; Agol, Vadim I

2009-10-01

62

Interactions between Viral and Prokaryotic Pathogens in a Mixed Infection with Cardiovirus and Mycoplasma?  

PubMed Central

In the natural environment, animal and plant viruses often share ecological niches with microorganisms, but the interactions between these pathogens, although potentially having important implications, are poorly investigated. The present report demonstrates, in a model system, profound mutual effects of mycoplasma and cardioviruses in animal cell cultures. In contrast to mycoplasma-free cells, cultures contaminated with Mycoplasma hyorhinis responded to infection with encephalomyocarditis virus (EMCV), a picornavirus, but not with poliovirus (also a picornavirus), with a strong activation of a DNase(s), as evidenced by the TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) immunofluorescence assay and electrophoretic analysis of host DNA. This degradation was reminiscent of that observed upon apoptosis but was caspase independent, judging by the failure of the specific pan-caspase inhibitor Q-VD-OPh to prevent it. The electrophoretic mobility of the enzyme responsible for DNA degradation and dependence of its activity on ionic conditions strongly suggested that it was represented by a DNase(s) of mycoplasma origin. In cells not infected with EMCV, the relevant DNase was dormant. The possibility is discussed that activation of the mycoplasma DNase might be linked to a relatively early increase in permeability of plasma membrane of the infected cells caused by EMCV. This type of unanticipated virus-mycoplasma “cooperation” may exemplify the complexity of pathogen-host interactions under conditions when viruses and microorganisms are infecting the same host. In the course of the present study, it was also demonstrated that pan-caspase inhibitor zVAD(OMe).fmk strongly suppressed cardiovirus polyprotein processing, illustrating an additional pitfall in investigations of viral effects on the apoptotic system of host cells. PMID:19605479

Lidsky, Peter V.; Romanova, Lyudmila I.; Kolesnikova, Marina S.; Bardina, Maryana V.; Khitrina, Elena V.; Hato, Stanleyson V.; van Kuppeveld, Frank J. M.; Agol, Vadim I.

2009-01-01

63

Development of Real-Time PCR Array for Simultaneous Detection of Eight Human Blood-Borne Viral Pathogens  

PubMed Central

Background Real-time PCR array for rapid detection of multiple viral pathogens should be highly useful in cases where the sample volume and the time of testing are limited, i.e. in the eligibility testing of tissue and organ donors. Findings We developed a real-time PCR array capable of simultaneously detecting eight human viral pathogens: human immunodeficiency virus types 1 and 2 (HIV-1 and -2), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus-1 and -2 (HTLV-1 and -2), vaccinia virus (VACV) and West Nile virus (WNV). One hundred twenty (120) primers were designed using a combination of bioinformatics approaches, and, after experimental testing, 24 primer sets targeting eight viral pathogens were selected to set up the array with SYBR Green chemistry. The specificity and sensitivity of the virus-specific primer sets selected for the array were evaluated using analytical panels with known amounts of viruses spiked into human plasma. The array detected: 10 genome equivalents (geq)/ml of HIV-2 and HCV, 50 geq of HIV-1 (subtype B), HBV (genotype A) and WNV. It detected 100–1,000 geq/ml of plasma of HIV-1 subtypes (A – G), group N and CRF (AE and AG) isolates. Further evaluation with a panel consisting of 28 HIV-1 and HIV-2 clinical isolates revealed no cross-reactivity of HIV-1 or HIV-2 specific primers with another type of HIV. All 28 viral isolates were identified with specific primer sets targeting the most conserved genome areas. The PCR array correctly identified viral infections in a panel of 17 previously quantified clinical plasma samples positive for HIV-1, HCV or HBV at as low as several geq per PCR reaction. Conclusions The viral array described here demonstrated adequate performance in the testing of donors’ clinical samples. Further improvement in its sensitivity for the broad spectrum of HIV-1 subtypes is under development. PMID:22912836

Pripuzova, Natalia; Wang, Richard; Tsai, Shien; Li, Bingjie; Hung, Guo-Chiuan; Ptak, Roger G.; Lo, Shyh-Ching

2012-01-01

64

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

Microsoft Academic Search

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

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

2010-01-01

65

Development of a real-time multiplex PCR assay for detection of viral pathogens of penaeid shrimp  

Microsoft Academic Search

A real-time multiplex polymerase chain reaction (rtm-PCR) assay was developed and optimized to simultaneously detect three\\u000a viral pathogens of shrimp in one reaction. Three sets of specific oligonucleotide primers for white spot syndrome virus (WSSV),\\u000a infectious hypodermal and haematopoietic necrosis virus (IHHNV) and Taura syndrome virus (TSV), along with three TaqMan probes\\u000a specific for each virus were used in the

Zhixun Xie; Liji Xie; Yaoshan Pang; Zhaofa Lu; Zhiqin Xie; Jianhua Sun; Xianwen Deng; Jiabo Liu; Xiaofei Tang; Mazhar Khan

2008-01-01

66

Inactivation of bacterial and viral fish pathogens by ozonation or UV irradiation in water of different salinity  

Microsoft Academic Search

Bacterial and viral fish pathogens were exposed to ozone or ultraviolet (UV) irradiation in laboratory batch systems. Inactivation curves were made for Aeromonas salmonicida subsp. salmonicida, Vibrio anguillarum, Vibrio salmonicida, Yersinia ruckeri and the infectious pancreatic necrosis virus (IPNV) in ozonated lake, brackish and sea water at 9–12°C. The four bacteria tested were inactivated by 99·99% (4 log reductions in

Helge Liltved; Halvor Hektoen; Harry Efraimsen

1995-01-01

67

Seroprevalences to Viral Pathogens in Free-Ranging and Captive Cheetahs (Acinonyx jubatus) on Namibian Farmland?  

PubMed Central

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

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

2010-01-01

68

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

PubMed Central

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

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

2014-01-01

69

Fate and transport of zoonotic, bacterial, viral, and parasitic pathogens during swine manure treatment, storage, and land application.  

PubMed

Members of the public are always somewhat aware of foodborne and other zoonotic pathogens; however, recent illnesses traced to produce and the emergence of pandemic H1N1 influenza virus have increased the scrutiny on all areas of food production. The Council for Agricultural Science and Technology has recently published a comprehensive review of the fate and transport of zoonotic pathogens that can be associated with swine manure. The majority of microbes in swine manure are not zoonotic, but several bacterial, viral, and parasitic pathogens have been detected. Awareness of the potential zoonotic pathogens in swine manure and how treatment, storage, and handling affect their survival and their potential to persist in the environment is critical to ensure that producers and consumers are not at risk. This review discusses the primary zoonotic pathogens associated with swine manure, including bacteria, viruses, and parasites, as well as their fate and transport. Because the ecology of microbes in swine waste is still poorly described, several recommendations for future research are made to better understand and reduce human health risks. These recommendations include examination of environmental and ecological conditions that contribute to off-farm transport and development of quantitative risk assessments. PMID:20348375

Ziemer, C J; Bonner, J M; Cole, D; Vinjé, J; Constantini, V; Goyal, S; Gramer, M; Mackie, R; Meng, X J; Myers, G; Saif, L J

2010-04-01

70

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

PubMed Central

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

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

2013-01-01

71

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

E-print Network

1994; Tompkins, White & Boots 2003; Torchin & Mitchell 2004; Mitchell et al. 2006; Borer et al. 2007b in Pacific Coast grasslands Eric W. Seabloom1 *, Elizabeth T. Borer1 , Anna Jolles2 and Charles E. Mitchell3 of pathogens (Mitchell et al. 2006). In addition, environmental factors can alter pathogen prevalence

Crews, Stephen

72

Are Ranaviruses Capable of Contributing to Species Declines?  

E-print Network

of Ranavirus Die-offs First Isolated: ·Dr. Allan Granoff ·R i i (1962) ·St. Jude Hospital ·Rana pipiens (1962 Ambystomatidae Salamandridae Norman Wells, NWT >30 States & 5 Provinces; 25 Spp Uncommon Lithobates sylvaticus

Gray, Matthew

73

Mutations in the Cytoplasmic Domain of the Newcastle Disease Virus Fusion Protein Confer Hyperfusogenic Phenotypes Modulating Viral Replication and Pathogenicity  

PubMed Central

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

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

2013-01-01

74

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

PubMed Central

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

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

75

to identify surface proteins from viral and bacterial pathogens that share structural fea-  

E-print Network

that the effects on plant growth of rising night-time temperatures are opposite to those of increasing daytime with host-cell ligands. Reasoning that interactions of ligand mimics with host recep- tors might facilitate pathogen adhesion and access to host cells, the researchers then tested

Myneni, Ranga B.

76

A New Ranavirus Isolated from Pseudacris clarkii Tadpoles in Playa Wetlands in the Southern High Plains, Texas  

Microsoft Academic Search

Mass die-offs of amphibian populations pose a challenging problem for conservation biologists. Ranaviruses often cause systemic infections in amphibians and, in North America, are especially virulent and lethal to larvae and metamorphs. In this paper we describe a novel ranavirus isolate as well as the first recorded occurrence of ranavirus in the southern High Plains of Texas and in associated

Shannon M. Torrence; D. Earl Green; Catherine J. Benson; Hon S. Ip; Loren M. Smith; Scott T. McMurry

2010-01-01

77

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

PubMed Central

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

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

2014-01-01

78

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

PubMed Central

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

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

79

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

PubMed Central

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

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

2014-01-01

80

Dose and host characteristics influence virulence of ranavirus infections  

Microsoft Academic Search

Parasites play a prominent role in the ecology, evolution, and more recently, conservation of many organisms. For example,\\u000a emerging infectious diseases, including a group of lethal ranaviruses, are associated with the declines and extinctions of\\u000a amphibians around the world. An increasingly important basic and applied question is: what controls parasite virulence? We\\u000a used a dose-response experiment with three laboratory-bred clutches

Jesse L. Brunner; Kathryn Richards; James P. Collins

2005-01-01

81

Complete Genome Sequence of a Ranavirus Isolated from Chinese Giant Salamander (Andrias davidianus)  

PubMed Central

A ranavirus (RV) was isolated from Chinese giant salamanders (Andrias davidianus) in China in 2010 and provisionally designated Andrias davidianus ranavirus (ADRV). The complete genome sequence is 106,719 nucleotides long. Genomic sequence and phylogenetic analyses showed that ADRV has a high degree of conservation with other RVs. PMID:24407629

Wang, Na; Zhang, Min; Zhang, Lifeng; Jing, Hongli; Jiang, Yulin; Lin, Xiangmei

2014-01-01

82

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

PubMed

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

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

2011-07-18

83

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

PubMed Central

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

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

2011-01-01

84

Viral Pathogens and Acute Lung Injury: Investigations Inspired by the SARS Epidemic and the 2009 H1N1 Influenza Pandemic  

PubMed Central

Acute viral pneumonia is an important cause of acute lung injury (ALI), although not enough is known about the exact incidence of viral infection in ALI. Polymerase chain reaction-based assays, direct fluorescent antigen (DFA) assays, and viral cultures can detect viruses in samples from the human respiratory tract, but the presence of the virus does not prove it to be a pathogen, nor does it give information regarding the interaction of viruses with the host immune response and bacterial flora of the respiratory tract. The severe acute respiratory syndrome (SARS) epidemic and the 2009 H1N1 influenza pandemic provided a better understanding of how viral pathogens mediate lung injury. Although the viruses initially infect the respiratory epithelium, the relative role of epithelial damage and endothelial dysfunction has not been well defined. The inflammatory host immune response to H1N1 infection is a major contributor to lung injury. The SARS coronavirus causes lung injury and inflammation in part through actions on the nonclassical renin angiotensin pathway. The lessons learned from the pandemic outbreaks of SARS coronavirus and H1N1 capture key principles of virally mediated ALI. There are pathogen-specific pathways underlying virally mediated ALI that converge onto a common end pathway resulting in diffuse alveolar damage. In terms of therapy, lung protective ventilation is the cornerstone of supportive care. There is little evidence that corticosteroids are beneficial, and they might be harmful. Future therapeutic strategies may be targeted to specific pathogens, the pathogenetic pathways in the host immune response, or enhancing repair and regeneration of tissue damage. PMID:23934716

Hendrickson, Carolyn M.; Matthay, Michael A.

2014-01-01

85

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

NASA Astrophysics Data System (ADS)

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.

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

1993-05-01

86

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

NASA Astrophysics Data System (ADS)

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.

Daaboul, George

87

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

PubMed Central

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

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

2005-01-01

88

Development of slide ELISA (SELISA) for detection of four poultry viral pathogens by direct heat fixation of viruses on glass slides.  

PubMed

The development of an easy and simpler method of slide enzyme-linked immunosorbent assay (SELISA) for the diagnosis of four economically important poultry viruses viz., Newcastle disease virus (NDV), infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV) and egg drop syndrome 76 virus (EDS 76) and the use of SELISA for semi quantitation of NDV are described. The positive signals for viral aggregates were detected under light microscope. This is the first report regarding the development of SELISA based on heat fixation for the diagnosis of viral pathogens. PMID:25218174

Desingu, P A; Singh, S D; Dhama, K; Vinodh Kumar, O R; Singh, R; Singh, R K

2014-12-01

89

Viral infection  

PubMed Central

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

Puigdomenech, Isabel; de Armas-Rillo, Laura; Machado, Jose-David

2011-01-01

90

PCR detection of ranavirus in adult anurans from the Louisville Zoological Garden.  

PubMed

Ranaviruses are known to cause mortality in a variety of anuran species and have the potential to significantly impact wild and captive frog populations. In this study, 16 captive frogs and toads from the Louisville Zoological Garden were examined for the presence of ranavirus; this group included 14 Cope's grey tree frogs (Hyla chrysoscelis), an American toad (Bufo americanus), and a southern toad (Bufo terrestris). All animals were wild caught and were evaluated via polymerase chain reaction (PCR), while animals that died were also assessed via histologic study to understand the role of ranaviral disease in these specimens. Of the animals that died, 82% were positive for ranavirus via PCR. Multiple swab samples collected over time from live tree frogs were positive for ranavirus via PCR. These findings reveal that ranaviral infection in captive adult anurans may occur without clinical signs or consistent histopathologic lesions. PMID:19746873

Driskell, Elizabeth A; Miller, Debra L; Swist, Shannon L; Gyimesi, Zoltan S

2009-09-01

91

Broad Distribution of Ranavirus in Free-Ranging Rana dybowskii in Heilongjiang, China  

Microsoft Academic Search

Ranaviruses have been associated with die-offs in cultured amphibians in China, but their presence in wild amphibians has\\u000a not yet been assessed. We sampled free-ranging Rana dybowskii at seven sites throughout Heilongjiang Province to determine the presence and prevalence of ranaviruses in this region. Our\\u000a results revealed an overall infection prevalence of 5.7% (18\\/315) for adults and 42.5% (51\\/120) for

Kai Xu; Dong-Ze Zhu; Ying Wei; Lisa M. Schloegel; Xiao-Feng Chen; Xiao-Long Wang

2010-01-01

92

Combined administration in a single injection of a feline multivalent modified live vaccine against FHV, FCV, and FPLV together with a recombinant FeLV vaccine is both safe and efficacious for all four major feline viral pathogens  

Microsoft Academic Search

Nobivac Tricat, a lyophilised trivalent modified live attenuated vaccine is routinely used to protect cats against three commonly diagnosed feline viral pathogens namely herpesvirus, calicivirus and panleukopenia virus. The recognition of feline leukaemia virus (FeLV) as an important viral pathogen has prompted the development of an efficacious liquid recombinant subunit FeLV vaccine (p45 envelope protein). Lyophilised Tricat vaccine was dissolved

Theo Kanellos; David J. Sutton; Claire F. Salisbury; William. Stuart K. Chalmers

2008-01-01

93

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

PubMed Central

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

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

2010-01-01

94

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

PubMed

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

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

2010-01-01

95

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

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

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

2013-01-01

96

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

PubMed

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

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

2013-05-01

97

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

PubMed

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

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

2013-07-22

98

Evaluation of a polyclonal antibody for the detection and identification of ranaviruses from freshwater fish and amphibians.  

PubMed

A rabbit polyclonal antibody (PAb) raised against European catfish virus (ECV; isolated from black bullhead Ameiurus melas in France) was produced and then evaluated using a panel of 9 ranavirus isolates collected from different lower vertebrate species originating from Australia, North and South America, Southeast Asia, and Europe. Using ranavirus-infected epithelioma papillosum cyprini (EPC) cell cultures, the specificity of the PAb was determined by Western blot, immunogold electron microscopy, and direct enzyme-linked immunosorbent assay (ELISA). Western blot analysis demonstrated that the PAb reacted strongly with a protein with a molecular weight corresponding to approximately 49 kDa. Immunogold electron microscopy provided direct evidence that the epitopes recognized by this PAb were located on the outer surface of virions. The PAb was used for the preparation of a peroxidase-labeled conjugate for the direct ELISA detection of ranaviruses in infected EPC cell cultures. The specificity of the conjugated PAb was tested using ranaviruses, some representative fish viruses of the genera Rhabdovirus and Birnavirus, and samples from various non-infected fish species. The PAb detected all tested ranaviruses except for 2 Santee-Cooper ranaviruses. The direct ELISA enabled the detection of ranavirus from a concentration of 10(3.5) to 10(3.8) TCID50 ml(-1) cell culture. The results of this study revealed that the rabbit PAb raised against ECV could be useful for the development of specific and standardized diagnostic assays for the detection of ranaviruses from freshwater fish and amphibians. PMID:20481086

Cinkova, Katerina; Reschova, Stanislava; Kulich, Pavel; Vesely, Tomas

2010-04-01

99

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

PubMed

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

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

2011-08-01

100

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

PubMed

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

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

2011-04-01

101

Conventional inactivated bivalent H5/H7 vaccine prevents viral localization in muscles of turkeys infected experimentally with low pathogenic avian influenza and highly pathogenic avian influenza H7N1 isolates.  

PubMed

Highly pathogenic avian influenza (HPAI) viruses cause viraemia and systemic infections with virus replication in internal organs and muscles; in contrast, low pathogenicity avian influenza (LPAI) viruses produce mild infections with low mortality rates and local virus replication. There is little available information on the ability of LPAI viruses to cause viraemia or on the presence of avian influenza viruses in general in the muscles of infected turkeys. The aim of the present study was to determine the ability of LPAI and HPAI H7N1 viruses to reach muscle tissues following experimental infection and to determine the efficacy of vaccination in preventing viraemia and meat localization. The potential of infective muscle tissue to act as a source of infection for susceptible turkeys by mimicking the practice of swill-feeding was also investigated. The HPAI virus was isolated from blood and muscle tissues of all unvaccinated turkeys; LPAI could be isolated only from blood of one bird and could be detected only by reverse transcriptase-polymerase chain reaction in muscles. In contrast, no viable virus or viral RNA could be detected in muscles of vaccinated/challenged turkeys, indicating that viral localization in muscle tissue is prevented in vaccinated birds. PMID:18622857

Toffan, Anna; Serena Beato, Maria; De Nardi, Roberta; Bertoli, Elena; Salviato, Annalisa; Cattoli, Giovanni; Terregino, Calogero; Capua, Ilaria

2008-08-01

102

A new ranavirus isolated from Pseudacris clarkii tadpoles in playa wetlands in the southern High Plains, Texas.  

PubMed

Mass die-offs of amphibian populations pose a challenging problem for conservation biologists. Ranaviruses often cause systemic infections in amphibians and, in North America, are especially virulent and lethal to larvae and metamorphs. In this paper we describe a novel ranavirus isolate as well as the first recorded occurrence of ranavirus in the southern High Plains of Texas and in associated populations of the spotted chorus frog Pseudacris clarkii. The breeding sites were playas, that is, wetlands that fill via isolated thunderstorms that can occur infrequently; thus, not every playa has water or breeding amphibians annually. We did not detect ranavirus in sympatric anurans, but other reports document ranaviruses in Pseudacris spp. elsewhere. The occurrence of multiple isolates of ranavirus in a number of Pseudacris species suggests that this genus of frogs is highly susceptible to ranaviruses and may experience exceptionally high mortality rates from infection. Thus, the virus may contribute to substantial seasonal population declines and low seasonal recruitment, with negative impacts on populations of breeding adults in successive years. PMID:20848879

Torrence, Shannon M; Green, D Earl; Benson, Catherine J; Ip, Hon S; Smith, Loren M; McMurry, Scott T

2010-06-01

103

Detection of major bacterial and viral pathogens in trash fish used to feed cultured flounder in Korea  

Microsoft Academic Search

The possibility of trash fish food-direct pathogen infection to cultured flounder is a very important concern of fish farmers in Korea. A total of 26 groups of trash fish and shrimp samples were collected from 11 hatcheries on Jeju Island. Four groups and two groups of homogenized frozen trash fish samples were directly isolated and confirmed by PCR assays with

Ji Hyung Kim; Dennis K. Gomez; Casiano H. Choresca; Se Chang Park

2007-01-01

104

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

SciTech Connect

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.

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

2007-04-11

105

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

E-print Network

-blooded animals (such as freshwater turtles) that come in contact with the virus in water or by eating live or dead infected individuals may also succumb to the disease. After a ranavirus outbreak, aquatic). Matthew J. Gray, Ph.D., CWB, is an Associate Professor of Wildlife Ecology in the Center for Wildlife

Gray, Matthew

106

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

E-print Network

-offs of farmed Chinese giant salamanders (Andrias davidianus) in Leshan, Sichuan Province, China. The farmed to the natural infections. Our data suggested that the virus isolate was a novel member of the genus Ranavirus, family Iridoviridae. We tentatively named the virus as Chinese giant salamander virus (CGSV-L). CGSV

Gray, Matthew

107

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

E-print Network

Genomic sequence of a ranavirus (family Iridoviridae) associated with salamander mortalities 2003; accepted 1 August 2003 Abstract Disease is among the suspected causes of amphibian population), are implicated in salamander die-offs in Arizona and Canada, respectively. We report the complete sequence

108

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

PubMed

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

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

2012-10-01

109

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

PubMed Central

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

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

2012-01-01

110

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

PubMed

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

Forzán, María J; Wood, John

2013-10-01

111

The Laurentian Great Lakes strain (MI03) of the viral haemorrhagic septicaemia virus is highly pathogenic for juvenile muskellunge, Esox masquinongy (Mitchill).  

PubMed

The Great Lakes strain of viral haemorrhagic septicaemia virus (VHSV) isolated from adult subclinical muskellunge, Esox masquinongy (Mitchill), in Lake St. Clair, MI, USA was shown to be highly pathogenic in juvenile muskellunge through intraperitoneal (i.p.) injection and waterborne challenge. Mortality began as early as 3 days after exposure in waterborne challenged fish, whereas fish infected by the i.p. route experienced the first mortality by 5 days post-infection (p.i.). The median lethal intraperitoneal injection dose (IP-LD(50)) was approximately 2.21 plaque forming units (PFU) as opposed to the median lethal immersion challenge dose (IM-LD(50)) of 1.7 x 10(4) PFU mL(-1). A high, medium and low dose of infection caused acute, subacute and chronic progression of the disease, respectively, as was evident by the cumulative mortality data. Clinical signs of disease observed in dead and moribund fish were very pale gills, dermal petechial haemorrhages along the flanks, severe nuchal haemorrhages, intramuscular haemorrhages at the fin-muscle junction and focal haemorrhaging on the caudal peduncle. Internal lesions included livers that were pale, discoloured and friable, and kidneys that were either congested or degenerative in appearance, and petechial to ecchymotic haemorrhages on the swim bladder wall. Histopathologic examination demonstrated massive haemorrhages in the swimbladder wall and muscle, severe vacuolation and multifocal necrosis of the liver, multifocal necrosis of the gills and depletion of lymphoid tissues within the spleen. Kidney tissues also exhibited a mixed pattern of degeneration that included tubular necrosis, interstitial oedema and congestion. Virus was recovered from kidney and spleen tissues through tissue culture and reverse transcriptase-polymerase chain reaction (RT-PCR). PMID:20367742

Kim, R K; Faisal, M

2010-06-01

112

Viral determinants of simian immunodeficiency virus (SIV) virulence in rhesus macaques assessed by using attenuated and pathogenic molecular clones of SIVmac.  

PubMed Central

To identify viral determinants of simian immunodeficiency virus (SIV) virulence, two pairs of reciprocal recombinants constructed from a pathogenic (SIVmac239) and a nonpathogenic (SIVmac1A11) molecular clone of SIV were tested in rhesus macaques. A large 6.2-kb fragment containing gag, pol, env, and the regulatory genes from each of the cloned (parental) viruses was exchanged to produce one pair of recombinant viruses (designated SIVmac1A11/239gag-env/1A11 and SIVmac239/1A11gag-env/239 to indicate the genetic origins of the 5'/internal/3' regions, respectively, of the virus). A smaller 1.4-kb fragment containing the external env domain of each of the parental viruses was exchanged to create the second pair (SIVmac1A11/239env/1A11 and SIVmac239/1A11env/239) of recombinant viruses. Each of the two parental and four recombinant viruses was inoculated intravenously into four rhesus macaques, and all 24 animals were viremic by 4 weeks postinoculation (p.i.). Virus could not be isolated from peripheral blood mononuclear cells (PBMC) of any animals infected with SIVmac1A11 after 6 weeks p.i. but was consistently isolated from all macaques inoculated with SIVmac239 for 92 weeks p.i. Virus isolation was variable from animals infected with recombinant viruses; SIVmac1A11/239gag-env/1A11 and SIVmac239/1A11env/239 were isolated most frequently. Animals inoculated with SIVmac239 had 10 to 100 times more virus-infected PBMC than those infected with recombinant viruses. Three animals infected with SIVmac239 died with simian AIDS (SAIDS) during the 2-year observation period after inoculation, and the fourth SIVmac239-infected animal had clinical signs of SAIDS. Two animals infected with recombinant viruses died with SAIDS; one was infected with SIVmac239/1A11gag-env/239, and the other was infected with SIVmac1A11/239gag-env/1A11. The remaining 18 macaques remained healthy by 2 years p.i., and 13 were aviremic. One year after inoculation, peripheral lymph nodes of some of these healthy, aviremic animals harbored infected cells. All animals seroconverted within the first few weeks of infection, and the magnitude of antibody response to SIV was proportional to the levels and duration of viremia. Virus-suppressive PBMC were detected within 2 to 4 weeks p.i. in all animals but tended to decline as viremia disappeared. There was no association of levels of cell-mediated virus-suppressive activity and either virus load or disease progression. Taken together, these results indicate that differences in more than one region of the viral genome are responsible for the lack of virulence of SIVmac1A11. PMID:8371353

Marthas, M L; Ramos, R A; Lohman, B L; Van Rompay, K K; Unger, R E; Miller, C J; Banapour, B; Pedersen, N C; Luciw, P A

1993-01-01

113

Ranaviruses (family Iridoviridae ): emerging cold-blooded killers  

Microsoft Academic Search

Summary.  ?Although possessing novel replicative and structural features, the family Iridoviridae has not been as extensively studied as other families of large, DNA-containing viruses (e.g., poxviridae and herpesviridae). This oversight most likely reflects the inability of iridoviruses to infect mammals and birds, and their heretofore low\\u000a pathogenicity among cold-blooded animals and invertebrates. In fact, the original frog virus isolates (e.g., frog

V. G. Chinchar

2002-01-01

114

Conventional inactivated bivalent H5\\/H7 vaccine prevents viral localization in muscles of turkeys infected experimentally with low pathogenic avian influenza and highly pathogenic avian influenza H7N1 isolates  

Microsoft Academic Search

Highly pathogenic avian influenza (HPAI) viruses cause viraemia and systemic infections with virus replication in internal organs and muscles; in contrast, low pathogenicity avian influenza (LPAI) viruses produce mild infections with low mortality rates and local virus replication. There is little available information on the ability of LPAI viruses to cause viraemia or on the presence of avian influenza viruses

Anna Toffan; Maria Serena Beato; Roberta De Nardi; Elena Bertoli; Annalisa Salviato; Giovanni Cattoli; Calogero Terregino; Ilaria Capua

2008-01-01

115

Cytokine determinants of viral tropism  

Microsoft Academic Search

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

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

2009-01-01

116

Quantification system for the viral dynamics of a highly pathogenic simian/human immunodeficiency virus based on an in vitro experiment and a mathematical model  

PubMed Central

Background Developing a quantitative understanding of viral kinetics is useful for determining the pathogenesis and transmissibility of the virus, predicting the course of disease, and evaluating the effects of antiviral therapy. The availability of data in clinical, animal, and cell culture studies, however, has been quite limited. Many studies of virus infection kinetics have been based solely on measures of total or infectious virus count. Here, we introduce a new mathematical model which tracks both infectious and total viral load, as well as the fraction of infected and uninfected cells within a cell culture, and apply it to analyze time-course data of an SHIV infection in vitro. Results We infected HSC-F cells with SHIV-KS661 and measured the concentration of Nef-negative (target) and Nef-positive (infected) HSC-F cells, the total viral load, and the infectious viral load daily for nine days. The experiments were repeated at four different MOIs, and the model was fitted to the full dataset simultaneously. Our analysis allowed us to extract an infected cell half-life of 14.1 h, a half-life of SHIV-KS661 infectiousness of 17.9 h, a virus burst size of 22.1 thousand RNA copies or 0.19 TCID50, and a basic reproductive number of 62.8. Furthermore, we calculated that SHIV-KS661 virus-infected cells produce at least 1 infectious virion for every 350 virions produced. Conclusions Our method, combining in vitro experiments and a mathematical model, provides detailed quantitative insights into the kinetics of the SHIV infection which could be used to significantly improve the understanding of SHIV and HIV-1 pathogenesis. The method could also be applied to other viral infections and used to improve the in vitro determination of the effect and efficacy of antiviral compounds. PMID:22364292

2012-01-01

117

Viral Phylodynamics  

PubMed Central

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

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

2013-01-01

118

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

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;

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

2007-01-01

119

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

Microsoft Academic Search

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

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

1999-01-01

120

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

PubMed Central

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

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

2013-01-01

121

Serological survey of selected canine viral pathogens and zoonoses in grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) from Alaska.  

PubMed

Between 1988 and 1991, 644 serum samples were collected from 480 grizzly bears (Ursus arctos horribilis) and 40 black bears (Ursus americanus) from Alaska, United States of America, and were tested for selected canine viral infections and zoonoses. Antibody prevalence in grizzly bears was 0% for parvovirus, 8.3% (40/480) for distemper, 14% (68/480) for infectious hepatitis, 16.5% (79/480) for brucellosis, 19% (93/480) for tularaemia and 47% (225/478) for trichinellosis. In black bears, prevalence ranged from 0% for distemper and parvovirus to 27.5% for trichinellosis and 32% for tularaemia. Antibody prevalence for brucellosis (2.5%) and tularaemia (32%) were identical for grizzly bears and black bears from the geographical area of interior Alaska. Links between differences in prevalence and the origin of the grizzly bears were observed. Antibodies to canine distemper virus and infectious hepatitis virus were mainly detected in grizzly bears from Kodiak Island and the Alaskan Peninsula. Brucellosis antibodies were prevalent in grizzly bears from western and northern Alaska, whereas tularaemia antibodies were detected in grizzly bears from interior Alaska and the Arctic. There was a strong gradient for antibodies to Trichinella spp. from southern to northern Alaska. For most diseases, antibody prevalence increased with age. However, for several infections, no antibodies were detected in grizzly bears aged from 0 to 2 years, in contrast to the presence of those infections in black bears. Grizzly bears served as excellent sentinels for surveillance of zoonotic infections in wildlife in Alaska. PMID:9850547

Chomel, B B; Kasten, R W; Chappuis, G; Soulier, M; Kikuchi, Y

1998-12-01

122

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

PubMed

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

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

2013-11-01

123

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

PubMed Central

In order to assess the microbial water quality in canal waters throughout the Florida Keys, a survey was conducted to determine the concentration of microbial fecal indicators and the presence of human pathogenic microorganisms. A total of 19 sites, including 17 canal sites and 2 nearshore water sites, were assayed for total coliforms, fecal coliforms, Escherichia coli, Clostridium perfringens, enterococci, coliphages, F-specific (F+) RNA coliphages, Giardia lamblia, Cryptosporidium parvum, and human enteric viruses (polioviruses, coxsackie A and B viruses, echoviruses, hepatitis A viruses, Norwalk viruses, and small round-structured viruses). Numbers of coliforms ranged from <1 to 1,410, E. coli organisms from <1 to 130, Clostridium spp. from <1 to 520, and enterococci from <1 to 800 CFU/100 ml of sample. Two sites were positive for coliphages, but no F+ phages were identified. The sites were ranked according to microbial water quality and compared to various water quality standards and guidelines. Seventy-nine percent of the sites were positive for the presence of enteroviruses by reverse transcriptase PCR (polioviruses, coxsackie A and B viruses, and echoviruses). Sixty-three percent of the sites were positive for the presence of hepatitis A viruses. Ten percent of the sites were positive for the presence of Norwalk viruses. Ninety-five percent of the sites were positive for at least one of the virus groups. These results indicate that the canals and nearshore waters throughout the Florida Keys are being impacted by human fecal material carrying human enteric viruses through current wastewater treatment strategies such as septic tanks. Exposure to canal waters through recreation and work may be contributing to human health risks. PMID:10473424

Griffin, Dale W.; Gibson, Charles J.; Lipp, Erin K.; Riley, Kelley; Paul, John H.; Rose, Joan B.

1999-01-01

124

[Viral hepatitis].  

PubMed

Viral hepatitis is associated with significant morbidity and mortality worldwide. Hepatitis A and E viruses are enterally transmitted and lead to usually self-limited acute hepatitis. Hepatitis B, C and D viruses are transmitted by parenteral routes and can lead to chronic hepatitis with progression to liver cirrhosis and hepatocellular carcinoma. Here, we briefly review current understanding and new developments in the virology and epidemiology, diagnosis, natural history, therapy and prevention of viral hepatitis. PMID:21452137

Moradpour, Darius; Blum, Hubert E

2011-04-01

125

Viral rhinitis  

Microsoft Academic Search

Viral rhinitis is a common, morbid, and costly malady, often complicated by otitis media, sinusitis, and asthma. Current therapies\\u000a are relatively ineffective and aimed at reducing symptoms rather than moderating underlying mechanisms. Nasal elevations of\\u000a proinflammatory cytokines track symptom expression during viral rhinitis, and it is hypothesized that these chemicals orchestrate\\u000a a common response to infection with many different viruses

Deborah A. Gentile; David P. Skoner

2001-01-01

126

ISOLATION AND PARTIAL SEQUENCING OF A FV-3-LIKE RANAVIRUS FROM THE CARCASS OF A JUVENILE EASTERN PAINTED TURTLE (Chrysemys picta picta)  

E-print Network

PAINTED TURTLE (Chrysemys picta picta) L. Iwanowicz, C. Densmore, C. Hahn U.S. Geological Survey, Leetown Science Center Kearneysville, WV. USA In the Spring of 2006, a painted turtle carcass recoveredISOLATION AND PARTIAL SEQUENCING OF A FV-3-LIKE RANAVIRUS FROM THE CARCASS OF A JUVENILE EASTERN

Gray, Matthew

127

Viral meningitis.  

PubMed

Viral meningitis is part of the aseptic meningitis syndrome but must be distinguished from bacterial meningitis on the basis of a careful examination of the CSF and sound clinical judgment. Enteroviruses probably account for the bulk of cases of aseptic meningitis that occur in the United States and which are reported to the Centers for Disease Control each year. The seasonal pattern in the incidence of aseptic meningitis is largely due to the seasonal variation of enteroviral infections. Early on, the CSF in patients with viral meningitis frequently contains a predominance of polymorphonuclear leukocytes and may even have a low glucose level. The presence of neutrophils in the initial CSF sample is especially common in patients with enteroviral infections. A CSF glucose level lower than 50 per cent of a simultaneously drawn blood glucose determination is not uncommon in patients with viral meningitis due to mumps, LCM, and herpes simplex. In a patient with a predominance of polymorphonuclear leukocytes in the initial CSF specimen and in whom a viral infection is suspected, antibiotics may be withheld if a spinal tap is repeated within 12 hours. A shift from polymorphonuclear leukocytes to mononuclear cells makes viral meningitis the likely diagnosis. Both herpes simplex and varicella-zoster may infect the meninges by means of spread from cervical and dorsal root ganglia in a retrograde fashion much the way they spread in an antegrade fashion to the skin. HSV-2 is more likely to cause the clinical syndrome of viral meningitis, while HSV-1 is more likely to cause a meningoencephalitis with serious brain dysfunction. The identification of a specific viral agent in body fluids, especially the CSF, in a patient with aseptic meningitis is of more than academic interest, since it can shorten duration of hospital stay and eliminate unnecessary antimicrobial therapy. The diagnosis of enteroviral infections depends upon the isolation of a virus from CSF, stool, or throat plus a fourfold antibody response in the serum to the viral isolate. The 60-odd serotypes of enterovirus, each with different antigenic determinants, preclude serologic testing alone as a useful diagnostic test to identify the patient infected with coxsackievirus or echovirus. For infections, due to herpes simplex, varicella-zoster, LCM, and arboviruses, a serologic test alone can be useful.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3990441

Ratzan, K R

1985-03-01

128

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

PubMed

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

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

2014-11-01

129

VIRAL GASTROENTERITIS  

EPA Science Inventory

Two virus types have been clearly shown to have epidemiologic importance in viral gastroenteritis, i.e., rotavirus and Norwalk virus. Four other virus types have been associated with gastroenteritis but their epidemiologic importance is not yet known, i.e., enteric adenovirus, ca...

130

Sumoylation at the Host-Pathogen Interface  

PubMed Central

Many viral proteins have been shown to be sumoylated with corresponding regulatory effects on their protein function, indicating that this host cell modification process is widely exploited by viral pathogens to control viral activity. In addition to using sumoylation to regulate their own proteins, several viral pathogens have been shown to modulate overall host sumoylation levels. Given the large number of cellular targets for SUMO addition and the breadth of critical cellular processes that are regulated via sumoylation, viral modulation of overall sumoylation presumably alters the cellular environment to ensure that it is favorable for viral reproduction and/or persistence. Like some viruses, certain bacterial plant pathogens also target the sumoylation system, usually decreasing sumoylation to disrupt host anti-pathogen responses. The recent demonstration that Listeria monocytogenes also disrupts host sumoylation, and that this is required for efficient infection, extends the plant pathogen observations to a human pathogen and suggests that pathogen modulation of host sumoylation may be more widespread than previously appreciated. This review will focus on recent aspects of how pathogens modulate the host sumoylation system and how this benefits the pathogen. PMID:23795346

Wilson, Van G.

2012-01-01

131

Human adenovirus: Viral pathogen with increasing importance.  

PubMed

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

Ghebremedhin, B

2014-03-01

132

Human adenovirus: Viral pathogen with increasing importance  

PubMed Central

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

2014-01-01

133

Unexpected rarity of the pathogen Batrachochytrium dendrobatidis in Appalachian Plethodon Salamanders: 1957-2011.  

PubMed

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

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

2014-01-01

134

Ranavirus-associated morbidity and mortality in a group of captive eastern box turtles (Terrapene carolina carolina).  

PubMed

Seven captive eastern box turtles (Terrapene carolina carolina) from a large collection of North American chelonians in North Carolina became acutely ill in the fall of 2002. Five of the turtles died. Clinical signs included cutaneous abscessation, oral ulceration or abscessation (or both), respiratory distress, anorexia, and lethargy. The predominant postmortem lesion was fibrinoid vasculitis of various organs, including skin, mucous membranes, lungs, and liver. No inclusion bodies were detected by histopathology or electron microscopy of formalin-fixed tissue. An iridovirus was isolated from tissues obtained postmortem from two of the box turtles that died. The virus was characterized by electron microscopy, polymerase chain reaction, and sequence analysis of a portion of the major capsid protein as a member of the genus Ranavirus. PMID:15732597

De Voe, Ryan; Geissler, Kyleigh; Elmore, Susan; Rotstein, David; Lewbart, Greg; Guy, James

2004-12-01

135

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...

136

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

Microsoft Academic Search

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

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

2002-01-01

137

Viral vectors for vaccine applications  

PubMed Central

Traditional approach of inactivated or live-attenuated vaccine immunization has resulted in impressive success in the reduction and control of infectious disease outbreaks. However, many pathogens remain less amenable to deal with the traditional vaccine strategies, and more appropriate vaccine strategy is in need. Recent discoveries that led to increased understanding of viral molecular biology and genetics has rendered the used of viruses as vaccine platforms and as potential anti-cancer agents. Due to their ability to effectively induce both humoral and cell-mediated immune responses, viral vectors are deemed as an attractive alternative to the traditional platforms to deliver vaccine antigens as well as to specifically target and kill tumor cells. With potential targets ranging from cancers to a vast number of infectious diseases, the benefits resulting from successful application of viral vectors to prevent and treat human diseases can be immense. PMID:23858400

Choi, Youngjoo

2013-01-01

138

DC-SIGN: escape mechanism for pathogens  

Microsoft Academic Search

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

Teunis B. H. Geijtenbeek; Yvette van Kooyk

2003-01-01

139

Viral Quasispecies Evolution  

PubMed Central

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

Sheldon, Julie; Perales, Celia

2012-01-01

140

Viral miniproteins.  

PubMed

Many viruses encode short transmembrane proteins that play vital roles in virus replication or virulence. Because many of these proteins are less than 50 amino acids long and not homologous to cellular proteins, their open reading frames were often overlooked during the initial annotation of viral genomes. Some of these proteins oligomerize in membranes and form ion channels. Other miniproteins bind to cellular transmembrane proteins and modulate their activity, whereas still others have an unknown mechanism of action. Based on the underlying principles of transmembrane miniprotein structure, it is possible to build artificial small transmembrane proteins that modulate a variety of biological processes. These findings suggest that short transmembrane proteins provide a versatile mechanism to regulate a wide range of cellular activities, and we speculate that cells also express many similar proteins that have not yet been discovered. PMID:24742054

DiMaio, Daniel

2014-09-01

141

Viral Hijackers  

NSDL National Science Digital Library

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 virusesâif 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.

Engineering K-Phd Program

142

Mortality Rates Differ Among Amphibian Populations Exposed to Three Strains of a Lethal Ranavirus  

Microsoft Academic Search

Infectious diseases are a growing threat to biodiversity, in many cases because of synergistic effects with habitat loss,\\u000a environmental contamination, and climate change. Emergence of pathogens as new threats to host populations can also arise\\u000a when novel combinations of hosts and pathogens are unintentionally brought together, for example, via commercial trade or\\u000a wildlife relocations and reintroductions. Chytrid fungus (Batrachochytrium dendrobatidis)

Danna M. Schock; Trent K. Bollinger; James P. Collins

2009-01-01

143

Host–Pathogen Systems Biology  

Microsoft Academic Search

\\u000a Unlike traditional biological research that focuses on a small set of components, systems biology studies the complex interactions\\u000a among a large number of genes, proteins, and other elements of biological networks and systems. Host-pathogen systems biology\\u000a examines the interactions between the components of two distinct organisms: a microbial or viral pathogen and its animal host.\\u000a With the availability of complete

Christian V. Forst

144

Diagnostics and discovery in viral hemorrhagic fevers.  

PubMed

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

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

2009-09-01

145

Coxsackieviral replication and pathogenicity: lessons from gene modified animal models  

Microsoft Academic Search

Coxsackieviruses have been implicated in the pathogenesis of human myocarditis and some forms of dilated cardiomyopathy. A considerable portion of our knowledge about the pathophysiology of viral heart disease is derived from animal studies. In particular, investigations utilising gene-targeted mice provide valuable new insights into various aspects of viral pathogenicity and host factors involved in the control of viral replication.

Rainer Wessely

2004-01-01

146

Central roles of NLRs and inflammasomes in viral infection  

Microsoft Academic Search

The immune response to viral infections is determined by a complex interplay between the pathogen and the host. Innate immune cells express a set of cytosolic sensors to detect viral infection. Recognition by these sensors induces the production of type I interferons and the assembly of inflammasome complexes that activate caspase-1, leading to production of interleukin-1? (IL-1?) and IL-18. Here,

Thirumala-Devi Kanneganti

2010-01-01

147

Signal perception in plant pathogen defense  

Microsoft Academic Search

Highly sensitive and specific recognition systems for microbial pathogens are essential for disease resistance in plants. Structurally diverse elicitors from various pathogens have been identified and shown to trigger plant defense mechanisms. Elicitor recognition by the plant is assumed to be mediated by receptors. Plant receptors for fungus-derived elicitors appear to reside preferentially in the plasma membrane, whereas viral and

T. Nürnberger

1999-01-01

148

Viral haemorrhagic fevers  

Microsoft Academic Search

Viral haemorrhagic fevers are viral infections that can cause shock, haemorrhage and multi-organ dysfunction. Their geographical distribution is limited by the ecology of their vectors, and many of them exist in tropical zones. The most common viral haemorrhagic fevers are not transmissible from person to person, and no viral haemorrhagic fevers are a threat to casual contacts. However, four viruses

Barbara Bannister

2005-01-01

149

NLRs, inflammasomes, and viral infection  

PubMed Central

NLR proteins are innate immune sensors that respond to microbial infection. Upon pathogen infection, some NLR proteins form large complexes, called inflammasomes, which activate caspase-1 and induce the production of active IL-1? and IL-18. Activation of inflammasomes can also lead to an inflammatory cell death program, named pyroptosis. In this review, we will discuss the role of various NLR proteins in sensing different viral infections, as well as the strategies used by several RNA and DNA viruses to counteract the antiviral effects of NLR-dependent inflammasomes. PMID:22581934

Jacobs, Sarah R.; Damania, Blossom

2012-01-01

150

Pathogenesis of the viral hemorrhagic fevers.  

PubMed

Four families of enveloped RNA viruses, filoviruses, flaviviruses, arenaviruses, and bunyaviruses, cause hemorrhagic fevers. These viruses are maintained in specific natural cycles involving nonhuman primates, bats, rodents, domestic ruminants, humans, mosquitoes, and ticks. Vascular instability varies from mild to fatal shock, and hemorrhage ranges from none to life threatening. The pathogenic mechanisms are extremely diverse and include deficiency of hepatic synthesis of coagulation factors owing to hepatocellular necrosis, cytokine storm, increased permeability by vascular endothelial growth factor, complement activation, and disseminated intravascular coagulation in one or more hemorrhagic fevers. The severity of disease caused by these agents varies tremendously; there are extremely high fatality rates in Ebola and Marburg hemorrhagic fevers, and asymptomatic infection predominates in yellow fever and dengue viral infections. Although ineffective immunity and high viral loads are characteristic of several viral hemorrhagic fevers, severe plasma leakage occurs at the time of viral clearance and defervescence in dengue hemorrhagic fever. PMID:23121052

Paessler, Slobodan; Walker, David H

2013-01-24

151

Severe Viral Infections and Primary Immunodeficiencies  

PubMed Central

Patients with severe viral infections are often not thoroughly evaluated for immunodeficiencies. In this review, we summarize primary immunodeficiencies that predispose individuals to severe viral infections. Some immunodeficiencies enhance susceptibility to disease with a specific virus or family of viruses, whereas others predispose to diseases with multiple viruses in addition to disease with other microbes. Although the role of cytotoxic T cells in controlling viral infections is well known, a number of immunodeficiencies that predispose to severe viral diseases have recently been ascribed to defects in the Toll-like receptor–interferon signaling pathway. These immunodeficiencies are rare, but it is important to identify them both for prognostic information and for genetic counseling. Undoubtedly, additional mutations in proteins in the innate and adaptive arms of the immune system will be identified in the future, which will reveal the importance of these proteins in controlling infections caused by viruses and other pathogens. PMID:21960712

Cohen, Jeffrey I.

2011-01-01

152

Complete Genome Sequence of the European Sheatfish Virus  

PubMed Central

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

Mavian, Carla; Lopez-Bueno, Alberto; Fernandez Somalo, Maria Pilar; Alcami, Antonio

2012-01-01

153

Dual role of commensal bacteria in viral infections  

PubMed Central

Summary With our capabilities to culture and sequence the commensal bacteria that dwell on and within a host, we can now study the host in its entirety, as a supraorganism that must be navigated by the pathogen invader. At present, the majority of studies have focused on the interaction between the host’s microbiota and bacterial pathogens. This is not unwarranted, given that bacterial pathogens must compete with commensal organisms for the limited territory afforded by the host. However, viral pathogens also enter the host through surfaces coated with microbial life and encounter an immune system shaped by this symbiotic community. Therefore, we believe the microbiota cannot be ignored when examining the interplay between the host and viral pathogens. Here we review work that details mechanisms by which the microbiota either promotes or inhibits viral replication and virally-induced pathogenesis. The impact of the microbitota on viral infection promises to be a new and exciting avenue of investigation, which will ultimately lead to better treatments and preventions of virally-induced diseases. PMID:23947358

Wilks, Jessica; Beilinson, Helen; Golovkina, Tatyana V.

2013-01-01

154

Broad-Spectrum Drugs Against Viral Agents  

PubMed Central

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

Christopher, Mary E.; Wong, Jonathan P.

2008-01-01

155

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

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

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

2010-01-01

156

Mitophagy in viral infections.  

PubMed

Antiviral innate immune responses and apoptosis are the two major factors limiting viral infections. Successful viral infection requires the virus to take advantage of the cellular machinery to bypass cellular defenses. Accumulated evidences show that autophagy plays a crucial role in cell-to-virus interaction. Here, we focus on how viruses subvert mitophagy to favor viral replication by mitigating innate immune responses and apoptotic signaling. PMID:25050805

Xia, Mao; Meng, Gang; Li, Min; Wei, Jiwu

2014-11-01

157

Prevention and treatment of viral diarrhea in pediatrics.  

PubMed

Diarrhea is the second largest cause of mortality worldwide in children from the perinatal period to the age of 5 years. Rotavirus has been the most commonly identified viral cause of diarrhea in children. Norovirus is now recognized as the second most common viral pathogen. Adenovirus, astrovirus and sapovirus are the other major viral causes of pediatric gastroenteritis. Strategies for prevention include basic hygiene, optimization of nutrition and, ultimately, vaccination. Two new vaccines have recently been licensed for the prevention of rotavirus, the monovalent human rotavirus vaccine (Rotarix) and the pentavalent bovine-human reassortant vaccine (RotaTeq). These vaccines have already dramatically decreased the morbidity associated with rotavirus in countries where they are widely used. Efforts to develop a norovirus vaccine face substantial hurdles. Treatment of the viral pathogens is primarily limited to symptomatic measures. PMID:20109050

Anderson, Evan J

2010-02-01

158

Viral Load Distribution in  

Microsoft Academic Search

An unprecedented community outbreak of severe acute respiratory syndrome (SARS) occurred in the Amoy Gardens, a high-rise residential complex in Hong Kong. Droplet, air, contaminated fomites, and rodent pests have been proposed to be mechanisms for transmitting SARS in a short period. We studied nasopharyngeal viral load of SARS patients on admission and their geographic distribu- tion. Higher nasopharyngeal viral

SARS Outbreak; Chung-Ming Chu; Vincent C. C. Cheng; Ivan F. N. Hung; Kin-Sang Chan; Bone S. F. Tang; Thomas H. F. Tsang; Kwok-Hung Chan; Kwok-Yung Yuen

2005-01-01

159

Viral Disease Networks?  

NASA Astrophysics Data System (ADS)

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.

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

2010-03-01

160

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

PubMed

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

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

2013-11-25

161

Memory in viral quasispecies.  

PubMed

Biological adaptive systems share some common features: variation among their constituent elements and continuity of core information. Some of them, such as the immune system, are endowed with memory of past events. In this study we provide direct evidence that evolving viral quasispecies possess a molecular memory in the form of minority components that populate their mutant spectra. The experiments have involved foot-and-mouth disease virus populations with known evolutionary histories. The composition and behavior of the viral population in response to a selective constraint were influenced by past evolutionary history in a way that could not be predicted from examination of consensus nucleotide sequences of the viral populations. The molecular memory of the viral quasispecies influenced both the nature and the intensity of the response of the virus to a selective constraint. PMID:10729128

Ruiz-Jarabo, C M; Arias, A; Baranowski, E; Escarmís, C; Domingo, E

2000-04-01

162

HIV Viral Load  

MedlinePLUS

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

163

Animal models for highly pathogenic emerging viruses  

PubMed Central

Exotic and emerging viral pathogens associated with high morbidity and mortality in humans are being identified annually with recent examples including Lujo virus in southern Africa, Severe fever with Thrombocytopenia virus in China and a SARS-like coronavirus in the Middle East. The sporadic nature of these infections hampers our understanding of these diseases and limits the opportunities to design appropriate medical countermeasures against them. Due to this, animal models are utilized to gain insight into the pathogenesis of disease with the overall goal of identifying potential targets for intervention and evaluating specific therapeutics and vaccines. For these reasons it is imperative that animal models of disease recapitulate the human condition as closely as possible in order to provide the best predictive data with respect to the potential efficacy in humans. In this article we review the current status of disease models for highly pathogenic and emerging viral pathogens. PMID:23403208

Safronetz, David; Geisbert, Thomas W.; Feldmann, Heinz

2013-01-01

164

Viral membrane fusion  

Microsoft Academic Search

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

Stephen C Harrison

2008-01-01

165

To Go Viral  

E-print Network

Mathematical models are validated against empirical data, while examining potential indicators for an online video that went viral. We revisit some concepts of infectious disease modeling (e.g. reproductive number) and we comment on the role of model parameters that interplay in the spread of innovations. The dataset employed here provides strong evidence that the number of online views is governed by exponential growth patterns, explaining a common feature of viral videos.

Cintron-Arias, Ariel

2014-01-01

166

The Fecal Viral Flora of Wild Rodents  

PubMed Central

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

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

2011-01-01

167

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

Microsoft Academic Search

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

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

2005-01-01

168

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

Microsoft Academic Search

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

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

2001-01-01

169

Ranaviruses in European reptiles  

E-print Network

in the liver and spleen · Virus detected by EM First reports #12;· Group of 7 juvenile Hermann`s tortoises, spleen, kidney, gonads · NOT from heart, brain, spinal cord ­ Animal 2: · Tongue · NOT from brain liver and spleen · Virus isolation in cell culture (TH-1) ­ From the tongue Fourth case: chelonians

Gray, Matthew

170

Pathogenic Human Viruses in Coastal Waters  

PubMed Central

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

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

2003-01-01

171

[Viral hepatitis in travellers].  

PubMed

Considering the geographical asymmetric distribution of viral hepatitis A, B and E, having a much higher prevalence in the less developed world, travellers from developed countries are exposed to a considerable and often underestimated risk of hepatitis infection. In fact a significant percentage of viral hepatitis occurring in developed countries is travel related. This results from globalization and increased mobility from tourism, international work, humanitarian and religious missions or other travel related activities. Several studies published in Europe and North America shown that more than 50% of reported cases of hepatitis A are travel related. On the other hand frequent outbreaks of hepatitis A and E in specific geographic areas raise the risk of infection in these restricted zones and that should be clearly identified. Selected aspects related with the distribution of hepatitis A, B and E are reviewed, particularly the situation in Portugal according to the published studies, as well as relevant clinical manifestations and differential diagnosis of viral hepatitis. Basic prevention rules considering enteric transmitted hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B) are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical situations and daily practice "pre travel" advice issues are discussed according to WHO/CDC recommendations and the Portuguese National Vaccination Program. Implications from near future availability of a hepatitis E vaccine, a currently in phase 2 trial, are highlighted. Potential indications for travellers to endemic countries like India, Nepal and some regions of China, where up to 30% of sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are considered. Continued epidemiological surveillance for viral hepatitis is essential to recognize and control possible outbreaks, but also to identify new viral hepatitis agents that may emerge as important global health issues. PMID:18331700

Abreu, Cândida

2007-01-01

172

Hepatitis E Virus (HEV) – An Emerging Viral Pathogen  

Microsoft Academic Search

\\u000a Hepatitis E virus (HEV) is the second major etiologic agent of enterically transmitted non-A, non-B hepatitis worldwide. HEV\\u000a is an unenveloped, single-stranded RNA virus having genome of approximately 8 kb in size. It is the sole member of the genus\\u000a Hepevirus in the family of Hepeviridae. Although it is most commonly recognised to occur in large outbreaks, HEV infection\\u000a accounts

Avrelija Cenci?; Walter Chingwaru

173

Avian Diagnostic and Therapeutic Antibodies to Viral Emerging Pathogens  

SciTech Connect

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.

David Bradley

2011-03-31

174

Polypyrrole nanoribbon based chemiresistive immunosensors for viral plant pathogen detection  

E-print Network

of cucumber mosaic virus (CMV). The sensitivity of the nano-immunosensors was enhanced by reducing Cucumber mosaic virus (CMV), the plant virus genus Cucumovi- rus (family Bromoviridae), is commonly found viruses, effective treatments have not been reported to prevent and/or eliminate CMV infection. Due

Chen, Wilfred

175

Experimental viral evolution to specific host MHC genotypes reveals fitness and virulence trade-offs  

E-print Network

are maintained. host-pathogen | antibiotic resistance | endangered species | pathogen escape of adaptive immunityExperimental viral evolution to specific host MHC genotypes reveals fitness and virulence trade and virulence evolution of a mouse-specific retrovirus to its mammalian host across multiple MHC genotypes

Potts, Wayne

176

KSHV Rta Promoter Specification and Viral Reactivation  

PubMed Central

Viruses are obligate intracellular pathogens whose biological success depends upon replication and packaging of viral genomes, and transmission of progeny viruses to new hosts. The biological success of herpesviruses is enhanced by their ability to reproduce their genomes without producing progeny viruses or killing the host cells, a process called latency. Latency permits a herpesvirus to remain undetected in its animal host for decades while maintaining the potential to reactivate, or switch, to a productive life cycle when host conditions are conducive to generating viral progeny. Direct interactions between many host and viral molecules are implicated in controlling herpesviral reactivation, suggesting complex biological networks that control the decision. One viral protein that is necessary and sufficient to switch latent Kaposi’s sarcoma-associated herpesvirus (KSHV) into the lytic infection cycle is called K-Rta. K-Rta is a transcriptional activator that specifies promoters by binding DNA directly and interacting with cellular proteins. Among these cellular proteins, binding of K-Rta to RBP-Jk is essential for viral reactivation. In contrast to the canonical model for Notch signaling, RBP-Jk is not uniformly and constitutively bound to the latent KSHV genome, but rather is recruited to DNA by interactions with K-Rta. Stimulation of RBP-Jk DNA binding requires high affinity binding of Rta to repetitive and palindromic “CANT DNA repeats” in promoters, and formation of ternary complexes with RBP-Jk. However, while K-Rta expression is necessary for initiating KSHV reactivation, K-Rta’s role as the switch is inefficient. Many factors modulate K-Rta’s function, suggesting that KSHV reactivation can be significantly regulated post-Rta expression and challenging the notion that herpesviral reactivation is bistable. This review analyzes rapidly evolving research on KSHV K-Rta to consider the role of K-Rta promoter specification in regulating the progression of KSHV reactivation. PMID:22347875

Guito, Jonathan; Lukac, David M.

2011-01-01

177

Transport of viral specimens.  

PubMed Central

The diagnosis of viral infections by culture relies on the collection of proper specimens, proper care to protect the virus in the specimens from environmental damage, and use of an adequate transport system to maintain virus activity. Collection of specimens with swabs that are toxic to either virus or cell culture should be avoided. A variety of transport media have been formulated, beginning with early bacteriological transport media. Certain swab-tube combinations have proven to be both effective and convenient. Of the liquid transport media, sucrose-based and broth-based media appear to be the most widely accepted and used. Studies on virus stability show that most viruses tested are sufficiently stable in transport media to withstand a transport time of 1 to 3 days. Some viruses may withstand longer transport times. In many cases, it is not necessary to store virus specimens in a refrigerator or send them to the laboratory on wet ice or frozen on dry ice. However, the specimen should not be exposed to environmental extremes. Modern viral transport media allow for more effective use of viral culture and culture enhancement techniques for the diagnosis of human viral infections. PMID:2187591

Johnson, F B

1990-01-01

178

Chronic viral diseases.  

PubMed Central

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

Berris, B

1986-01-01

179

Viral hemorrhagic fever  

Microsoft Academic Search

Viral hemorrhagic fever (VHF) is a severe, often fatal disease in humans and nonhuman primates (e.g., monkeys and chimpanzees). The two main causes of VHF are Marburg and Ebola virus infection. Lassa fever and Crimean-Congo hemorrhagic fever occur less commonly. Marburg and Ebola viruses are RNA filoviruses. Filoviruses first emerged as the cause of significant clinical outbreaks of VHF in

Amy Boardman

2003-01-01

180

[Viral encephalitis in children].  

PubMed

Viral encephalitis is a severe illness that produces inflammation of the brain. CNS viral infections frequently occur as a complication of systemic viral infections. Over 100 viruses are implicated as causative agents, including herpes simplex virus type I which is the most common agent implied in non-epidemic encephalitis in all population groups in the world, and is responsible for the most severe cases in all ages. Many viruses, for which there are vaccines, may also cause encephalitis: measles, mumps, polio, rabies, rubella, and chickenpox. The virus causes an inflammation of the brain tissue, which may progress to destruction of nerve cells, cause bleeding and brain damage, leading to severe encephalitis, such as hemorrhagic or necrotizing encephalitis, with a worse prognosis, producing serious sequelae or death. The clinical evolution includes the presence of headache, fever and altered consciousness rapidly progressive. The outcome of viral encephalitis is variable, some cases are mild, with full recovery, but there are serious cases that can cause severe sequel in the brain. To diagnose this illness as soon as possible is essential, through laboratory tests (biochemistry, virus PCR, culture) and neuroimaging (CT, MRI) and above all, the establishment of early treatment to prevent the development of the process and possible complications. The prognosis worsens if the initiation of treatment is delayed. PMID:24072056

Téllez de Meneses, Monserrat; Vila, Miguel T; Barbero Aguirre, Pedro; Montoya, José F

2013-01-01

181

Rapid Detection of Pathogens  

SciTech Connect

Pathogen identification is a crucial first defense against bioterrorism. A major emphasis of our national biodefense strategy is to establish fast, accurate and sensitive assays for diagnosis of infectious diseases agents. Such assays will ensure early and appropriate treatment of infected patients. Rapid diagnostics can also support infection control measures, which monitor and limit the spread of infectious diseases agents. Many select agents are highly transmissible in the early stages of disease, and it is critical to identify infected patients and limit the risk to the remainder of the population and to stem potential panic in the general population. Nucleic acid-based molecular approaches for identification overcome many of the deficiencies associated with conventional culture methods by exploiting both large- and small-scale genomic differences between organisms. PCR-based amplification of highly conserved ribosomal RNA (rRNA) genes, intergenic sequences, and specific toxin genes is currently the most reliable approach for bacterial, fungal and many viral pathogenic agents. When combined with fluorescence-based oligonucleotide detection systems, this approach provides real-time, quantitative, high fidelity analysis capable of single nucleotide allelic discrimination (4). These probe systems offer rapid turn around time (<2 h) and are suitable for high throughput, automated multiplex operations that are critical for clinical diagnostic laboratories. In this pilot program, we have used molecular beacon technology invented at the Public health Research Institute to develop a new generation of molecular probes to rapidly detect important agents of infectious diseases. We have also developed protocols to rapidly extract nucleic acids from a variety of clinical specimen including and blood and tissue to for detection in the molecular assays. This work represented a cooperative research development program between the Kramer-Tyagi/Perlin labs on probe development and the Perlin lab in sample preparation and testing in animal models.

David Perlin

2005-08-14

182

Common and unique features of viral RNA-dependent polymerases.  

PubMed

Eukaryotes and bacteria can be infected with a wide variety of RNA viruses. On average, these pathogens share little sequence similarity and use different replication and transcription strategies. Nevertheless, the members of nearly all RNA virus families depend on the activity of a virally encoded RNA-dependent polymerase for the condensation of nucleotide triphosphates. This review provides an overview of our current understanding of the viral RNA-dependent polymerase structure and the biochemistry and biophysics that is involved in replicating and transcribing the genetic material of RNA viruses. PMID:25080879

Te Velthuis, Aartjan J W

2014-11-01

183

Viral otitis media  

Microsoft Academic Search

Acute otitis media (AOM) and viral upper respiratory tract infections (URIs) represent the two most common diseases affecting\\u000a the human population, and account for substantial patient morbidity and health care costs. Epidemiologic and experimental\\u000a studies suggest that URIs play a causal role in the pathogenesis of AOM. Specifically, viruses can either invade the middle\\u000a ear (ME) space and invoke an

Craig A. Buchman; George M. Brinson

2003-01-01

184

Assessment of Virally Vectored Autoimmunity as a Biocontrol Strategy for Cane Toads  

PubMed Central

Background The cane toad, Bufo (Chaunus) marinus, is one of the most notorious vertebrate pests introduced into Australia over the last 200 years and, so far, efforts to identify a naturally occurring B. marinus-specific pathogen for use as a biological control agent have been unsuccessful. We explored an alternative approach that entailed genetically modifying a pathogen with broad host specificity so that it no longer caused disease, but carried a gene to disrupt the cane toad life cycle in a species specific manner. Methodology/Principal Findings The adult beta globin gene was selected as the model gene for proof of concept of autoimmunity as a biocontrol method for cane toads. A previous report showed injection of bullfrog tadpoles with adult beta globin resulted in an alteration in the form of beta globin expressed in metamorphs as well as reduced survival. In B. marinus we established for the first time that the switch from tadpole to adult globin exists. The effect of injecting B. marinus tadpoles with purified recombinant adult globin protein was then assessed using behavioural (swim speed in tadpoles and jump length in metamorphs), developmental (time to metamorphosis, weight and length at various developmental stages, protein profile of adult globin) and genetic (adult globin mRNA levels) measures. However, we were unable to detect any differences between treated and control animals. Further, globin delivery using Bohle iridovirus, an Australian ranavirus isolate belonging to the Iridovirus family, did not reduce the survival of metamorphs or alter the form of beta globin expressed in metamorphs. Conclusions/Significance While we were able to show for the first time that the switch from tadpole to adult globin does occur in B. marinus, we were not able to induce autoimmunity and disrupt metamorphosis. The short development time of B. marinus tadpoles may preclude this approach. PMID:21283623

Robinson, Anthony J.; Venables, Daryl; Voysey, Rhonda D.; Boyle, Donna G.; Shanmuganathan, Thayalini; Hardy, Christopher M.; Siddon, Nicole A.; Hyatt, Alex D.

2011-01-01

185

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

Microsoft Academic Search

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

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

2000-01-01

186

DISEASES OF AQUATIC ORGANISMS Dis Aquat Org  

E-print Network

2008, the World Organization for Animal Health (OIE) classified Ranavirus as a notifiable pathogen (OIE. There are no treatments or vaccinations currently available for ranaviruses (Robert et al. 2007). Captive ranaculture

Gray, Matthew

187

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

Microsoft Academic Search

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

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

1997-01-01

188

Viral entry mechanisms: the increasing diversity of paramyxovirus entry  

PubMed Central

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

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

2009-01-01

189

Inflammasomes and viruses: cellular defence versus viral offence.  

PubMed

Pro-inflammatory cytokines are important mediators in immune responses against invading pathogens, including viruses. Precursors of the pro-inflammatory cytokines interleukin (IL)-1? and IL-18 are processed by caspase-1. Caspase-1 is activated through autocleavage, but how this is regulated remained elusive for a long time. In 2002, an intracellular multimeric complex was discovered that facilitated caspase-1 cleavage and was termed 'inflammasome'. To date, different inflammasomes have been described, which recognize a variety of ligands and pathogens. In this review, we discuss the role of inflammasomes in sensing viral infection as well as the evasion strategies that viruses developed to circumvent inflammasome-dependent effects. PMID:22739062

Gram, Anna M; Frenkel, Joost; Ressing, Maaike E

2012-10-01

190

Defective viral genomes: critical danger signals of viral infections.  

PubMed

Viruses efficiently block the host antiviral response in order to replicate and spread before host intervention. The mechanism initiating antiviral immunity during stealth viral replication is unknown, but recent data demonstrate that defective viral genomes generated at peak virus replication are critical for this process in vivo. This article summarizes the supporting evidence and highlights gaps in our understanding of the mechanisms and impact of immunostimulatory defective viral genomes generated during natural infections. PMID:24872580

López, Carolina B

2014-08-01

191

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

PubMed

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

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

2014-08-01

192

Monitoring and managing viral infections in pediatric renal transplant recipients  

Microsoft Academic Search

Viral infections remain a significant cause of morbidity and mortality following renal transplantation. The pediatric cohort\\u000a is at high risk of developing virus-related complications due to immunological naiveté and the increased alloreactivity risk\\u000a that requires maintaining a heavily immunosuppressive environment. Although cytomegalovirus is the most common opportunistic\\u000a pathogen seen in transplant recipients, numerous other viruses may affect clinical outcome. Recent

Patrizia Comoli; Fabrizio Ginevri

193

Complete viral RNA genome sequencing of ultra-low copy samples by sequence-independent amplification  

PubMed Central

RNA viruses are the causative agents for AIDS, influenza, SARS, and other serious health threats. Development of rapid and broadly applicable methods for complete viral genome sequencing is highly desirable to fully understand all aspects of these infectious agents as well as for surveillance of viral pandemic threats and emerging pathogens. However, traditional viral detection methods rely on prior sequence or antigen knowledge. In this study, we describe sequence-independent amplification for samples containing ultra-low amounts of viral RNA coupled with Illumina sequencing and de novo assembly optimized for viral genomes. With 5 million reads, we capture 96 to 100% of the viral protein coding region of HIV, respiratory syncytial and West Nile viral samples from as little as 100 copies of viral RNA. The methods presented here are scalable to large numbers of samples and capable of generating full or near full length viral genomes from clone and clinical samples with low amounts of viral RNA, without prior sequence information and in the presence of substantial host contamination. PMID:22962364

Malboeuf, Christine M.; Yang, Xiao; Charlebois, Patrick; Qu, James; Berlin, Aaron M.; Casali, Monica; Pesko, Kendra N.; Boutwell, Christian L.; DeVincenzo, John P.; Ebel, Gregory D.; Allen, Todd M.; Zody, Michael C.; Henn, Matthew R.; Levin, Joshua Z.

2013-01-01

194

Cellular immune therapy for viral infections in transplant patients  

PubMed Central

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

Khanna, Rajiv; Smith, Corey

2013-01-01

195

Host and viral ecology determine bat rabies seasonality and maintenance  

PubMed Central

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

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.

2011-01-01

196

Host and viral ecology determine bat rabies seasonality and maintenance.  

PubMed

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

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

197

[Prevention of viral hepatitis].  

PubMed

Prevention of viral hepatitis infection involves health measures designed to avert transmission of viral agents and promote the use of gammaglobulin and vaccines. The availability of safe drinking water and improvements in quality of life result in better individual hygiene; these factors have had the greatest impact on hepatitis A prevention. Serum gammaglobulin administration has been replaced by vaccinations for pre-exposure, and to a great extent for post-exposure prophylaxis because of the progressively lower anti-HAV content of gammaglobulin and the short duration of the protective effect. Universal vaccination in childhood is the recommended measure for controlling hepatitis A. Adults belonging to high-risk groups should also undergo vaccination. The incidence of hepatitis B has decreased worldwide because of universal vaccination programs, initiated in preadolescence and childhood. Prevention of hepatitis C requires control of situations in which there is a likelihood of parenteral infection with the virus. Post-transfusion hepatitis has been virtually eradicated, but considerable effort is still needed to prevent nosocomial hepatitis. PMID:17194391

Bruguera, Miguel

2006-12-01

198

[Viral haemorrhagic fever].  

PubMed

Viral haemorrhagic fever denotes various kinds of febrile illness caused by certain viruses which often presents with bleeding tendency and occasionally shock. Out of these, the four maladies, Lassa fever, Ebola haemorrhagic fever, Marburg haemorrhagic fever and Crimean-Congo haemorrhagic fever which are endemically present in Africa or eastern Europe, are known to be such diseases with high man-to-man communicability. These four haemorrhagic fevers are, therefore, designated as special conditions requiring isolation during the period when the infected patients are shedding the viruses, not only in Japan but also in many other countries. We have so far only one such case of Lassa fever who returned to Japan from Sierra Leone in 1987. Some haemorrhagic fevers including dengue (haemorrhagic) fever and hantavirus infections (e.g. haemorrhagic fever with renal syndrome) are not known to be man-to-man transmissible and requiring no isolation. We have a number of dengue and dengue haemorrhagic fevers here in Japan today among imported febrile cases from tropical or subtropical countries. Every physician should take viral haemorrhagic fevers into consideration as one of the possibilities in diagnosing patients returning from overseas travel. PMID:9283226

Masuda, G

1997-08-01

199

Viral hepatitis in Bucharest.  

PubMed

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

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

1993-01-01

200

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

USGS Publications Warehouse

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

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

2013-01-01

201

Viral IRES RNA structures and ribosome interactions  

PubMed Central

In eukaryotes, protein synthesis initiates primarily by a mechanism that requires a modified nucleotide ‘cap’ on the mRNA and also proteins that recruit and position the ribosome. Many pathogenic viruses use an alternative, cap-independent mechanism that substitutes RNA structure for the cap and many proteins. The RNAs driving this process are called internal ribosome-entry sites (IRESs) and some are able to bind the ribosome directly using a specific 3D RNA structure. Recent structures of IRES RNAs and IRES–ribosome complexes are revealing the structural basis of viral IRES’ ‘hijacking’ of the protein-making machinery. It now seems that there are fundamental differences in the 3D structures used by different IRESs, although there are some common features in how they interact with ribosomes. PMID:18468443

Kieft, Jeffrey S.

2009-01-01

202

The Evolution of a `Tragedy of the Commons' in a Host-Pathogen Metapopulation Jevin West1, Antony Dean2, Claudia Neuhauser2, Brendan Bohannan3 & Benjamin Kerr1,2  

E-print Network

and evolution of disease. The host is the bacterium Escherichia coli and the pathogen is the virus T4 coliphage is Escherichia coli and its viral pathogen is T4 coliphage (Fig 1). The experiments (described

Bergstrom, Carl T.

203

[Viral hemorrhagic fever].  

PubMed

Viral haemorrhagic fevers, such as Lassa fever and yellow fever, cause tens of thousands of deaths annually outside the Netherlands. The viruses are mostly transmitted by mosquitoes, ticks or via excreta of rodents. Important to travellers are yellow fever, dengue and Lassa and Ebola fever. For yellow fever there is an efficacious vaccine. Dengue is frequently observed in travellers; prevention consists in avoiding mosquito bites, the treatment is symptomatic. Lassa and Ebola fever are extremely rare among travellers; a management protocol can be obtained from the Netherlands Ministry of Health, Welfare and Sports. Diagnostics of a patient from the tropics with fever and haemorrhagic diathesis should be aimed at treatable disorders such as malaria, typhoid fever, rickettsiosis or bacterial sepsis, because the probability of such a disease is much higher than that of Lassa or Ebola fever. PMID:9562757

Kager, P A

1998-02-28

204

Dengue viral infections  

PubMed Central

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

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

2004-01-01

205

A Strategy To Estimate Unknown Viral Diversity in Mammals  

PubMed Central

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

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

206

Innate immune responses of salmonid fish to viral infections.  

PubMed

Viruses are the most serious pathogenic threat to the production of the main aquacultured salmonid species the rainbow trout Oncorhynchus mykiss and the Atlantic salmon Salmo salar. The viral diseases Infectious Pancreatic Necrosis (IPN), Pancreatic Disease (PD), Infectious Haemorrhagic Necrosis (IHN), Viral Haemorrhagic Septicaemia (VHS), and Infectious Salmon Anaemia (ISA) cause massive economic losses to the global salmonid aquaculture industry every year. To date, no solution exists to treat livestock affected by a viral disease and only a small number of efficient vaccines are available to prevent infection. As a consequence, understanding the host immune response against viruses in these fish species is critical to develop prophylactic and preventive control measures. The innate immune response represents an important part of the host defence mechanism preventing viral replication after infection. It is a fast acting response designed to inhibit virus propagation immediately within the host, allowing for the adaptive specific immunity to develop. It has cellular and humoral components which act in synergy. This review will cover inflammation responses, the cell types involved, apoptosis, antimicrobial peptides. Particular attention will be given to the type I interferon system as the major player in the innate antiviral defence mechanism of salmonids. Viral evasion strategies will also be discussed. PMID:23981327

Collet, Bertrand

2014-04-01

207

Viral infections in mice with reconstituted human immune system components.  

PubMed

Pathogenic viruses are often difficult to study due to their exclusive tropism for humans. The development of mice with human immune system components opens the possibility to study those human pathogens with a tropism for the human hematopoietic lineage in vivo. These include HCMV, EBV, KSHV, HIV, HTLV-1, dengue virus and JC virus. Furthermore, some human pathogens, like HSV-2, adenovirus, HCV, HBV and influenza A virus, with an additional tropism for somatic mouse tissues or for additional transplanted human tissues, mainly liver, have been explored in these models. The cellular tropism of these viruses, their associated diseases and primarily cell-mediated immune responses to these viral infections will be discussed in this review. Already some exciting information has been gained from these novel chimeric in vivo models and future avenues to gain more insights into the pathology, but also potential therapies, will be outlined. Although the respective in vivo models of human immune responses can still be significantly improved, they already provide preclinical systems for in vivo studies of important viral pathogens of humans. PMID:24953718

Münz, Christian

2014-09-01

208

Nonlytic viral spread enhanced by autophagy components  

PubMed Central

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

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

2014-01-01

209

Detection of Viral Hemorrhagic Septicemia Virus  

E-print Network

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

unknown authors

210

Clinical and experimental aspects of viral myocarditis.  

PubMed Central

Picornaviruses are frequently implicated as the etiological agents of acute myocarditis. This association is based historically on serological evidence of rising antibody titers to specific pathogens and more recently on identification of viral genomic material in endocardial biopsy specimens through in situ hybridization. Only rarely is infectious virus isolated from either the patient or the heart during periods of maximum myocardial inflammation and injury. Thus, despite a probable viral etiology, much interest centers on the role of the immune system in cardiac damage and the likelihood that the infection triggers an autoimmune response to heart-specific antigens. Heart-reactive antibodies and T cells are found in most myocarditis patients, and immunosuppressive therapy has proven beneficial in many, though not all, cases. Furthermore, murine models of coxsackievirus group B type 3-induced myocarditis also demonstrate that virus infection initiates autoimmunity and that these autoimmune effectors are predominately responsible for tissue injury. How virus-host interactions overcome presumed self-tolerance to heart antigens is discussed, and evidence supporting various theories of virus-initiated autoimmunity and disease pathogenesis are delineated. PMID:2650861

Leslie, K; Blay, R; Haisch, C; Lodge, A; Weller, A; Huber, S

1989-01-01

211

[Viral encephalitis virus, a new bioterrorist menace].  

PubMed

Often responsible for little known infections, today viral encephalitis viruses appear as a new bioterrorist menace, because of their easy production and their great pathogenic potential. Spraying is the best way to permit the rapid diffusion of certain encephalitis viruses. Diagnosis of viral encephalitis, predominating in tropical surroundings, is difficult. In the majority of cases, symptoms differ little from those of common flu. With supplementary examinations, the biological abnormalities are usually non-specific. There are no characteristic images on scans or MRI. Identification of the virus in the nasopharynx, blood or cerebrospinal fluid, in serology, PCR or RT-PCR permits confirmation of the virus. Treatment is essentially symptomatic and relies on appropriate reanimation measures. Ribavirin can be indicated in some cases such as the Rift Valley fever, but is formally contraindicated in West Nile encephalitis. The aim of terrorist groups who would use this type of weapon is more to provoke panic and disorganisation than to kill as many people as possible. PMID:15687967

Rigaudeau, Sophie; Micol, Romain; Bricaire, François; Bossi, Philippe

2005-01-29

212

Potential lactoferrin activity against pathogenic viruses.  

PubMed

Lactoferrin (LF) is an 80-kDa globular glycoprotein with high affinity for metal ions, particularly for iron. This protein possesses many biological functions, including the binding and release of iron and serves as one of the important components of the innate immune system, where it acts as a potent inhibitor of several pathogens. LF has efficacious antibacterial and antiviral activities against a wide range of Gram-positive and Gram-negative bacteria and against both naked and enveloped DNA and RNA viruses. In its antiviral pursuit, LF acts predominantly at the acute phase of the viral infection or even at the intracellular stage, as in hepatitis C virus infection. LF inhibits the entry of viral particles into host cells, either by direct attachment to the viral particles or by blocking their cellular receptors. This wide range of activities may be attributed to the capacity of LF to bind iron and its ability to interfere with the cellular receptors of both hosts and pathogenic microbes. PMID:25282173

Redwan, Elrashdy M; Uversky, Vladimir N; El-Fakharany, Esmail M; Al-Mehdar, Hussein

2014-10-01

213

Mechanical Properties of Viral Capsids  

NASA Astrophysics Data System (ADS)

Viral genomes, whether they involve RNA or DNA molecules, are invariably protected by a rigid, single-protein-thick, shell referred to as ``capsid.'' Viral capsids are known to tolerate wide ranges of pH and salt conditions and to withstand internal pressures as high as 100 atms. We study the mechanical properties of viral capsids, calling explicit attention to the inhomogeneity of the shells that is inherent in their being discrete/polyhedral rather than continuous/spherical. We analyze the distribution of stress in these capsids due to isotropic internal pressure (arising, for instance, from genome confinement and/or osmotic activity), and compare the results with appropriate generalizations of classical elasticity theory. We also examine the competing mechanisms for viral shell failure, e.g., in-plane crack formation vs radial bursting. The biological consequences of the special stabilities and stress distributions of viral capsids are also discussed.

Zandi, Roya; Reguera, David

2005-03-01

214

Deep Sequencing to Identify the Causes of Viral Encephalitis  

PubMed Central

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

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

2014-01-01

215

Metagenomics-based analysis of viral communities in dairy lagoon wastewater.  

PubMed

Microbial populations, especially those of viruses, are poorly studied in dairy wastewater treatment operations. Here we report signature nucleic acid metagenomic sequences obtained by pyrosequencing viromes of virus-like particles that were extracted from two dairy waste treatment lagoons. The lagoons are operated in series, with Lagoon I being used as the primary stage and Lagoon II as the secondary stage of wastewater treatment. An average of 2000 sequences was obtained from each lagoon. More than 300 signatures from each lagoon matched sequences in the virus database of the National Center for Biotechnology Information (NCBI). We utilized a bioinformatics approach and transmission electron microscopy (TEM) to characterize the viral diversity and presence of potential viral pathogens within the lagoons. Our results showed differences in viral community compositions between Lagoon I and Lagoon II, suggesting that the viral community changes significantly in the transition of water between the two lagoons. Furthermore, the diverse viral community in the lagoon samples contained signature sequences of a variety of bacterial, plant, and animal viruses. Bacteriophage sequences dominated the viral community metagenomes in both lagoons. Ultimately these results can be used to identify viral bioindicators to rapidly assess wastewater treatment quality and the potential impacts of dairy operations on watersheds. Our viral metagenomic sequences have been submitted to GenBank (GPID 65805) and can provide insight into the composition and structure of viral communities within wastewaters of dairy lagoon systems. PMID:23220059

Alhamlan, F S; Ederer, M M; Brown, C J; Coats, E R; Crawford, R L

2013-02-15

216

137 Interplay between host defenses and viral anti-defenses as a major factor of viral cytopathogenicity  

PubMed Central

The prevailing paradigm posits that virus-induced cellular injuries (cytopathic effect, CPE) are caused by hijacking of cellular substrates, energy, and infrastructure by the pathogens for the needs of their reproduction. However, this appears to be not the sole, and even not the most important, mechanism of cellular pathology triggered by viral infections. There is ground to believe that the most severe harm may come not from viral reproduction as such but rather from (miscalculated) host defenses as well as from viral anti-defensive activities. The experiments to be presented strongly support this notion. By using as a model system HeLa cells infected with mengovirus (a strain of encephalomyocarditis virus, a lytic picornavirus), we show that the major signs of CPE caused by this virus can be uncoupled from its reproduction. This can be achieved by partial mutual disarmament of the virus (by mutational inactivation of one of its anti-defensive “security” proteins, the leader protein) and the host (by chemical inhibition of one of its defensive innate immunity mechanisms, apoptosis). Under such conditions, the appearance of major cellular injuries is postponed until well after the completion of the viral reproduction. Remarkably, a more profound disarmament of the virus (by additional deletion of its second security protein, 2A) accompanied with a marked suppression of the viral reproduction leads to a faster death of the infected apoptosis-deficient cells due primarily to their defensive suicidal programmed necrosis. Thus, efficient strategies to ameliorate virus-induced injuries may include measures aimed at suppression of not only viral reproduction or viral anti-host functions but also of host defenses.

Agol, Vadim I.

2014-01-01

217

RAB11-mediated trafficking in host-pathogen interactions.  

PubMed

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

Guichard, Annabel; Nizet, Victor; Bier, Ethan

2014-09-01

218

Pathogen Chip for Respiratory Tract Infections  

PubMed Central

Determining the viral etiology of respiratory tract infections (RTI) has been limited for the most part to specific primer PCR-based methods due to their increased sensitivity and specificity compared to other methods, such as tissue culture. However, specific primer approaches have limited the ability to fully understand the diversity of infecting pathogens. A pathogen chip system (PathChip), developed at the Genome Institute of Singapore (GIS), using a random-tagged PCR coupled to a chip with over 170,000 probes, has the potential to recognize all known human viral pathogens. We tested 290 nasal wash specimens from Filipino children <2 years of age with respiratory tract infections using culture and 3 PCR methods—EraGen, Luminex, and the GIS PathChip. The PathChip had good diagnostic accuracy, ranging from 85.9% (95% confidence interval [CI], 81.3 to 89.7%) for rhinovirus/enteroviruses to 98.6% (95% CI, 96.5 to 99.6%) for PIV 2, compared to the other methods and additionally identified a number of viruses not detected by these methods. PMID:23303493

Patel, Champa; Sung, Wing-Kin; Lee, Charlie W. H.; Loh, Kuan Hon; Lucero, Marilla; Nohynek, Hanna; Nai, Geraldine; Thien, Pei Ling; Koh, Chee Wee; Chan, Yang Sun; Ma, Jianmin; Maurer-Stroh, Sebastian; Carosone-Link, Phyllis; Hibberd, Martin L.; Wong, Christopher W.

2013-01-01

219

Pathogen chip for respiratory tract infections.  

PubMed

Determining the viral etiology of respiratory tract infections (RTI) has been limited for the most part to specific primer PCR-based methods due to their increased sensitivity and specificity compared to other methods, such as tissue culture. However, specific primer approaches have limited the ability to fully understand the diversity of infecting pathogens. A pathogen chip system (PathChip), developed at the Genome Institute of Singapore (GIS), using a random-tagged PCR coupled to a chip with over 170,000 probes, has the potential to recognize all known human viral pathogens. We tested 290 nasal wash specimens from Filipino children <2 years of age with respiratory tract infections using culture and 3 PCR methods-EraGen, Luminex, and the GIS PathChip. The PathChip had good diagnostic accuracy, ranging from 85.9% (95% confidence interval [CI], 81.3 to 89.7%) for rhinovirus/enteroviruses to 98.6% (95% CI, 96.5 to 99.6%) for PIV 2, compared to the other methods and additionally identified a number of viruses not detected by these methods. PMID:23303493

Simões, Eric A F; Patel, Champa; Sung, Wing-Kin; Lee, Charlie W H; Loh, Kuan Hon; Lucero, Marilla; Nohynek, Hanna; Nai, Geraldine; Thien, Pei Ling; Koh, Chee Wee; Chan, Yang Sun; Ma, Jianmin; Maurer-Stroh, Sebastian; Carosone-Link, Phyllis; Hibberd, Martin L; Wong, Christopher W

2013-03-01

220

Molecular Basis of Latency in Pathogenic Human Viruses  

NASA Astrophysics Data System (ADS)

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

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

1991-11-01

221

[Emerging viral diseases].  

PubMed

Emerging and re-emerging infectious diseases have again entered the public arena in recent years. This is due to factors such as evolving lifestyles, ecological and socio-political upheavals, and recent diagnostic advances. Numerous pathogens, including viruses like West Nile, Chikungunya and Japanese encephalitis on the one hand, and hemorrhagic fever viruses like Ebola and Maburg, are particular concerns. Recently, the Corona virus responsible for SARS, which caused an epidemic sufficiently worrisome to challenge crisis management concepts, was successfully isolated. It is in this context that so-called "bird flu'", may be on the verge of causing a human pandemic. Pox and Monkeypox are "virtually emerging" viruses that have potential for use in bioterrorism. The management and treatment of these emerging infectious diseases calls for new approaches, organizations and infrastructures. PMID:17140098

Bricaire, François; Bossi, Philippe

2006-03-01

222

DENGUE VIRAL INFECTIONS  

PubMed Central

Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF) occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections. PMID:20418983

Gurugama, Padmalal; Garg, Pankaj; Perera, Jennifer; Wijewickrama, Ananda; Seneviratne, Suranjith L

2010-01-01

223

Molecular basis of host specificity in human pathogenic bacteria  

PubMed Central

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.

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

2014-01-01

224

Polycistronic viral vectors.  

PubMed

Traditionally, vectors for gene transfer/therapy experiments were mono- or bicistronic. In the latter case, vectors express the gene of interest coupled with a marker gene. An increasing demand for more complex polycistronic vectors has arisen in recent years to obtain complex gene transfer/therapy effects. In particular, this demand is stimulated by the hope of a more powerful effect from combined gene therapy than from single gene therapy in a process whose parallels lie in the multi-drug combined therapies for cancer or AIDS. In the 1980's we had only splicing signals and internal promoters to construct such vectors: now a new set of biotechnological tools enables us to design new and more reliable bicistronic and polycistronic vectors. This article focuses on the description and comparison of the strategies for co-expression of two genes in bicistronic vectors, from the oldest to the more recently described: internal promoters, splicing, reinitiation, IRES, self-processing peptides (e.g. foot-and-mouth disease virus 2A), proteolytic cleavable sites (e.g. fusagen) and fusion of genes. I propose a classification of these strategies based upon either the use of multiple transcripts (with transcriptional mechanisms), or single transcripts (using translational/post-translational mechanisms). I also examine the different attempts to utilize these strategies in the construction of polycistronic vectors and the main problems encountered. Several potential uses of these polycistronic vectors, both in basic research and in therapy-focused applications, are discussed. The importance of the study of viral gene expression strategies and the need to transfer this knowledge to vector design is highlighted. PMID:12189721

de Felipe, P

2002-09-01

225

Mathematical models of viral latency.  

PubMed

While viral latency remains one of the biggest challenges for successful antiviral therapy, it has also inspired mathematical modelers to develop dynamical system approaches with the aim of predicting the impact of drug efficacy on disease progression and the persistence of latent viral reservoirs. In this review we present several differential equation models and assess their relative success in giving advice to the working clinician and their predictive power for inferring long term viral eradication from short term abatement. Many models predict that there is a considerable likelihood of viral rebound due to continuous reseeding of latent reservoirs. Most mathematical models of HIV latency suffer from being reductionist by ignoring the growing variety of different cell types harboring latent virus, the considerable intercellular delay involved in reactivation, and host-related epigenetic modifications which may alter considerably the dynamical system of immune cell populations. PMID:23896280

Selinger, Christian; Katze, Michael G

2013-08-01

226

Viruses of fish: an overview of significant pathogens.  

PubMed

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

Crane, Mark; Hyatt, Alex

2011-11-01

227

Viral RNAs Are Unusually Compact  

PubMed Central

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

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

2014-01-01

228

The role of IL-10 in regulating immunity to persistent viral infections.  

PubMed

The immune system has evolved multipronged responses that are critical to effectively defend the body from invading pathogens and to clear infection. However, the same weapons employed to eradicate infection can have caustic effects on normal bystander cells. Therefore, tight regulation is vital and the host must balance engendering correct and sufficient immune responses to pathogens while limiting errant and excessive immunopathology. To accomplish this task, a complex network of positive and negative immune signals are delivered, which in most instances successfully eliminate the pathogen. However, in response to some viral infections, immune function is rapidly suppressed leading to viral persistence. Immune suppression is a critical obstacle to the control of many persistent viral infections such as HIV, hepatitis C, and hepatitis B virus, which together affect more than 500 million individuals worldwide. Thus, the ability to therapeutically enhance immunity is a potentially powerful approach to resolve persistent infections. The host-derived cytokine IL-10 is a key player in the establishment and perpetuation of viral persistence. This chapter discusses the role of IL-10 in viral persistence and explores the exciting prospect of therapeutically blocking IL-10 to increase antiviral immunity and vaccine efficacy. PMID:20703965

Wilson, Elizabeth B; Brooks, David G

2011-01-01

229

The Structure of Marek Disease Virus DNA: The Presence of Unique Expansion in Nonpathogenic Viral DNA  

Microsoft Academic Search

DNA of Marek disease virus (MDV) consists of two unique regions UL and US flanked by long inverted repeat regions TRL and IRL, and short inverted repeat regions TRS and IRS, respectively, similar to herpes simplex virus DNA. Comparison of restriction patterns between pathogenic and nonpathogenic MDV DNA was made to identify a region of viral DNA different between these

K. Fukuchi; A. Tanaka; L. W. Schierman; R. L. Witter; M. Nonoyama

1985-01-01

230

CD46 Is a Cellular Receptor for Bovine Viral Diarrhea Virus  

Microsoft Academic Search

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

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

2004-01-01

231

Kinetics of Facultative Heterochromatin and Polycomb Group Protein Association with the Herpes Simplex Viral Genome during  

E-print Network

Center, University of North Carolina, Chapel Hill, North Carolina, USA. ABSTRACT The herpes simplex virus during latent infection of neurons. IMPORTANCE The human pathogen herpes simplex virus (HSV) hides protein association with the herpes simplex viral genome during establishment of latent infection. mBio 4

Knipe, David M.

232

Viral Vectors: A Wide Range of Choices and High Levels of Service  

Microsoft Academic Search

Viruses are intracellular parasites with simple DNA or RNA genomes. Virus life revolves around three steps: infection of a host cell, replication of its genome within the host cell environment, and formation of new virions; this process is often but not always associated with pathogenic effects against the host organism. Since the mid-1980s, the main goal of viral vectorology has

P. Osten; V. Grinevich; A. Cetin

233

Antigen quantification as in vitro alternative for potency testing of inactivated viral poultry vaccines  

Microsoft Academic Search

Routine batch control of licensed inactivated viral vaccines for poultry usually includes a potency assay as a measure of vaccine efficacy. Potency assays often consist of vaccination?challenge experiments in the target species or in laboratory animals. Instead of measuring the protection of vaccinated animals against virulent pathogens, the serological response after vaccination can be quantified for some vaccines. In vitro

P. A. Maas; M. P. M. de Winter; S. Venema; H. L. Oei; I. J. T. M. Claassen

2000-01-01

234

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

Microsoft Academic Search

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

MATTHIAS SCHWEIZER; ERNST PETERHANS

2001-01-01

235

Acute and Chronic Airway Responses to Viral Infection: Implications for Asthma and Chronic Obstructive Pulmonary Disease  

Microsoft Academic Search

Despite the high clinical impact of established and emerging respi- ratory viruses, some critical aspects of the host response to these pathogens still need to be defined. In that context, we aimed at two major issues: first, what are the innate immune mechanisms that control common respiratory viral infections; and second, whether these mechanisms also cause long-term airway disease. Using

Michael J. Holtzman; Jeffrey W. Tyner; Edy Y. Kim; Mindy S. Lo; Anand C. Patel; Laurie P. Shornick; Eugene Agapov; Yong Zhang

2005-01-01

236

[Treatment of viral hepatitis].  

PubMed

Chronic forms of viral B,C and D hepatitis and fulminant hepatitis represent a serious healthcare problem. The study deals with the changes in the strategy in treating these diseases. During the chronic active hepatitis caused by the B hepatitis virus, the main aim of treatment is to cease multiplication of viruses, eliminate the clinical symptoms, prevent the development of cirrhosis, or the origin of hepatocellular carcinoma. The authors analyze the possibilities of the application of corticosteroids, viricidal drugs (vidarabin and interferons) and other medicaments (acyclovir, zidovudin, duramin, gancyclovir, chinacrin, and others) besides corticosteroids, interleukin 2 and tymozin from the group of immunomodulators were tested. The testing included the factor stimulating the colonies of granulocytes and myeloblasts and other substances. The therapy of acute protracted B hepatitis by means of interferon still requires controlled studies. Superinfection by D virus in chronic carriers of HBsAG causes chronic hepatitis which quickly leads to the development of cirrhosis. The therapy on basis of alpha interferon decreases the RNA virus D hepatitis serum level and leads to an improvement in the development of chronic hepatitis in half of the patients. Therapy of chronic C hepatitis on basis of corticosteroids is ineffective, and can be dangerous. Acyclovir is proved to be ineffective as well. The open study indicated certain positive results in application of interferon. The fulminant hepatitis can be defined as a development of encephalopathy and a decrease of the prothrombin time to less than 50% in the course of acute hepatitis. The break-point in the therapy of fulminant hepatitis took place in association with the performance of the transplantation of the liver. Impossibility to transplant the liver means that the effect of therapy of fulminant hepatitis is merely of supportive value. Majority of patients die due to neurologic complications, namely unmanageable oedema of the brain. But still, neither the antioedema therapy, e.g. on basis of manitol, as well as by means of corticosteroids, hemodialysis, hemofiltration, plasmapheresis and hemoperfusion, nor the treatment on basis of E1 prostaglandine improved the survival of patients. (Tab. 2, Ref. 82). PMID:8556359

Miguet, J; Hrusovský, S

1995-09-01

237

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

PubMed Central

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

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

2014-01-01

238

Emerging Pathogens - How Safe is Blood?  

PubMed Central

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

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

2014-01-01

239

Detection of Viral Hemorrhagic Septicemia Virus  

E-print Network

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

unknown authors

240

Enteric Pathogens Associated with Childhood Diarrhea in Tripoli-Libya  

PubMed Central

Stool samples from children < 5 years of age with diarrhea (N = 239) were examined for enteric pathogens using a combination of culture, enzyme-immunoassay, and polymerase chain reaction methods. Pathogens were detected in 122 (51%) stool samples; single pathogens were detected in 37.2% and co-pathogens in 13.8% of samples. Norovirus, rotavirus, and diarrheagenic Escherichia coli (DEC) were the most frequently detected pathogens (15.5%, 13.4%, and 11.2%, respectively); Salmonella, adenovirus, and Aeromonas were detected less frequently (7.9%, 7.1%, and 4.2%). The most commonly detected DEC was enteroaggregative E. coli (5.4%). Resistance to ? 3 antimicrobials was observed in 60% (18/30) of the bacterial pathogens. Salmonella resistance to ciprofloxacin (63.1%) has become a concern. Enteric viral pathogens were the most significant causative agents of childhood diarrhea in Tripoli. Bacterial pathogens were also important contributors to pediatric diarrhea. The emergence of ciprofloxacin-resistant Salmonella represents a serious health problem that must be addressed by Libyan health authorities PMID:21633024

Rahouma, Amal; Klena, John D.; Krema, Zaineb; Abobker, Abdalwahed A.; Treesh, Khalid; Franka, Ezzedin; Abusnena, Omar; Shaheen, Hind I.; El Mohammady, Hanan; Abudher, Abdulhafid; Ghenghesh, Khalifa Sifaw

2011-01-01

241

Ranaviruses: Past, Present, and 1st Intl. Symposium of Ranaviruses,  

E-print Network

disease identified First Insect Iridovirus Identified FV3 identified FV3 Life Cycle Elucidated) ornate burrowing frog [AU ­ BIV] · Bloch and Larsen (1993) Turbot [Scandinavia] · Chua et al. (1994, but low mortality ­ Genus: Megalocytivirus lifethreatening infections in >52 8 Genus: Megalocytivirus...life

Gray, Matthew

242

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

NASA Astrophysics Data System (ADS)

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

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

2010-04-01

243

Epidemiology of the spread of viral diseases under aquaculture.  

PubMed

Aquaculture production is increasing rapidly worldwide. However, production has been associated with the emergence of several novel diseases, including viral diseases, that have caused serious problems for producers. Using examples largely from salmon farming in Scotland I review briefly the factors that allow transmission to occur in aquaculture. These include transmission through the water, which is relatively local to the infected farm, and anthropogenic transports (such as transport of fish between sites) that may occur over very long distances. A Disease Management Area (DMA) approach, as developed in Scotland to fight infectious salmon anaemia, can be effective at reducing pathogen transmission and hence disease emergence. PMID:23206337

Murray, Alexander G

2013-02-01

244

Epidemiology, etiology, x-ray features, importance of co-infections and clinical features of viral pneumonia in developing countries.  

PubMed

Pneumonia is still the number one killer of young children globally, accounting for 18% of mortality in children under 5 years of age. An estimated 120 million new cases of pneumonia occur globally each year. In developing countries, management and prevention efforts against pneumonia have traditionally focused on bacterial pathogens. More recently however, viral pathogens have gained attention as a result of improved diagnostic methods, such as polymerase chain reaction, outbreaks of severe disease caused by emerging pathogens, discovery of new respiratory viruses as well as the decrease in bacterial pneumonia as a consequence of the introduction of highly effective conjugate vaccines. Although the epidemiology, etiology and clinical characterization of viral infections are being studied extensively in the developed world, little data are available from low- and middle-income countries. In this paper, we review the epidemiology, etiology, clinical and radiological features of viral pneumonia in developing countries. PMID:24410617

Lanaspa, Miguel; Annamalay, Alicia A; LeSouëf, Peter; Bassat, Quique

2014-01-01

245

Mechanical properties of viral capsids  

NASA Astrophysics Data System (ADS)

Viruses are known to tolerate wide ranges of pH and salt conditions and to withstand internal pressures as high as 100atmospheres . In this paper we investigate the mechanical properties of viral capsids, calling explicit attention to the inhomogeneity of the shells that is inherent to their discrete and polyhedral nature. We calculate the distribution of stress in these capsids and analyze their response to isotropic internal pressure (arising, for instance, from genome confinement and/or osmotic activity). We compare our results with appropriate generalizations of classical (i.e., continuum) elasticity theory. We also examine competing mechanisms for viral shell failure, e.g., in-plane crack formation vs radial bursting. The biological consequences of the special stabilities and stress distributions of viral capsids are also discussed.

Zandi, Roya; Reguera, David

2005-08-01

246

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

PubMed

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

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

2014-11-01

247

Coinfection. Helminth infection reactivates latent ?-herpesvirus via cytokine competition at a viral promoter.  

PubMed

Mammals are coinfected by multiple pathogens that interact through unknown mechanisms. We found that helminth infection, characterized by the induction of the cytokine interleukin-4 (IL-4) and the activation of the transcription factor Stat6, reactivated murine ?-herpesvirus infection in vivo. IL-4 promoted viral replication and blocked the antiviral effects of interferon-? (IFN?) by inducing Stat6 binding to the promoter for an important viral transcriptional transactivator. IL-4 also reactivated human Kaposi's sarcoma-associated herpesvirus from latency in cultured cells. Exogenous IL-4 plus blockade of IFN? reactivated latent murine ?-herpesvirus infection in vivo, suggesting a "two-signal" model for viral reactivation. Thus, chronic herpesvirus infection, a component of the mammalian virome, is regulated by the counterpoised actions of multiple cytokines on viral promoters that have evolved to sense host immune status. PMID:24968940

Reese, T A; Wakeman, B S; Choi, H S; Hufford, M M; Huang, S C; Zhang, X; Buck, M D; Jezewski, A; Kambal, A; Liu, C Y; Goel, G; Murray, P J; Xavier, R J; Kaplan, M H; Renne, R; Speck, S H; Artyomov, M N; Pearce, E J; Virgin, H W

2014-08-01

248

Recent insights into the evolution of innate viral sensing in animals  

PubMed Central

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

Lewis, Samuel H; Obbard, Darren J

2014-01-01

249

Vaccines against dangerous pathogens  

Microsoft Academic Search

Dangerous pathogens are defined by the UK Health and Safety Executive's advisory committee as category 3 (those which cause severe human disease for which prophylaxis or therapy is usually available) or category 4 (as for category 3, but for which prophylaxis or therapy is not available). Research and development of vaccines for such pathogens is challenging, due to the safety

E D Williamson; R W Titball

2002-01-01

250

Emerging Escherichia pathogen.  

PubMed

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

Kaewpoowat, Quanhathai; Permpalung, Nitipong; Sentochnik, Deborah E

2013-08-01

251

Emerging Escherichia Pathogen  

PubMed Central

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

Permpalung, Nitipong; Sentochnik, Deborah E.

2013-01-01

252

BACTERIAL WATERBORNE PATHOGENS  

EPA Science Inventory

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

253

Plant pathogen resistance  

DOEpatents

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

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

2012-11-27

254

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

Microsoft Academic Search

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.

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

255

Therapy of chronic viral hepatitis.  

PubMed

Chronic infection with hepatitis B virus (HBV), the delta agent (HDV) or hepatitis C virus (HCV) carries high risks of chronic liver disease which can result in cirrhosis and hepatocellular carcinoma. Many antiviral agents have been tried to inhibit viral replication and thereby limit infectivity and the risks of eventual serious liver disease. Interferon offers a 30-40% chance of viral clearance to the hepatitis B carrier, offers a good chance of clinical response in parenterally acquired chronic non-A non-B hepatitis and may be of benefit for some patients with chronic delta infection. PMID:1716277

Main, J

1991-06-01

256

[Emerging viral diseases in Europe].  

PubMed

Emergence of viral agents in Europe is influenced by various factors. Climatic changes influencing possible vectors, insufficient vaccination, and travel of man and goods are among the most important reasons to explain these changes. Fever and arthralgia are the leading symptoms in infection with Dengue, Sindbis, or Chikungunya virus. In contrast, tick-born encephalitis (TBE), Toscana, or West Nile virus infections mainly lead to meningo-encephalitis. In Europe, hemorrhagic fever is caused by Crimean Congo and Hanta virus. Protective vaccines are available for emerging viral agents like TBE, influenza and measles. PMID:22511281

Löbermann, M; Gürtler, L G; Eichler-Löbermann, B; Reisinger, E C

2012-04-01

257

Rotavirus and other viral diarrhoeas*  

PubMed Central

Recent evidence indicates that viruses are an important cause of acute diarrhoea in infants and young children in both developed and developing countries. This article reviews the available information on the epidemiology, clinical features, and laboratory diagnosis of acute diarrhoea due to two of the more important and recently discovered viruses, namely rotaviruses and the Norwalk and Norwalk-like agents, or to other viral agents. Research priorities are also recommended that will help to elucidate the epidemiology, pathophysiology, and means of preventing viral diarrhoeas. Foremost among these research priorities is the development of a rotavirus vaccine for use in man. PMID:6249509

1980-01-01

258

Cytosolic Viral Sensor RIG-I Is a 5'-Triphosphate-Dependent Translocase on Double-Stranded RNA  

Microsoft Academic Search

Retinoic acid inducible-gene I (RIG-I) is a cytosolic multidomain protein that detects viral RNA and elicits an antiviral immune response. Two N-terminal caspase activation and recruitment domains (CARDs) transmit the signal, and the regulatory domain prevents signaling in the absence of viral RNA. 5'-triphosphate and double-stranded RNA (dsRNA) are two molecular patterns that enable RIG-I to discriminate pathogenic from self-RNA.

Sua Myong; Sheng Cui; Peter V. Cornish; Axel Kirchhofer; Michaela U. Gack; Jae U. Jung; Karl-Peter Hopfner; Taekjip Ha

2009-01-01

259

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

E-print Network

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

Chandran, Kartik

260

Post-extraction stabilization of HIV viral RNA for quantitative molecular tests  

PubMed Central

Two approaches to stabilize viral nucleic acid in processed clinical specimens were evaluated. HIV-1 RNA extracted from clinical specimens was stabilized in a dry matrix in a commercial product (RNAstable, Biomatrica, San Diego, CA, USA) and in a reverse-transcription reaction mixture in liquid form as cDNA. As few as 145 HIV-1 genome copies of viral RNA are reliably stabilized by RNAstable at 45°C for 92 days and in the cDNA format at 45°C for 7 days as determined by real-time PCR. With RNAstable the R2 at days 1, 7, and 92 were 0.888, 0.871, and 0.943 when compared to baseline viral load values. The cDNA generated from the same clinical specimens was highly stable with an R2 value of 0.762 when comparing viral load determinations at day 7 to baseline values. In conclusion viral RNA stabilized in a dry RNAstable matrix is highly stable for long periods of time at high temperatures across a substantial dynamic range. Viral RNA signal can also be stabilized in liquid in the form of cDNA for limited periods of time. Methods that reduce reliance on the cold chain and preserve specimen integrity are critical for extending the reach of molecular testing to low-resource settings. Products based on anhydrobiosis, such as the RNAstable should be evaluated further to support viral pathogen diagnosis. PMID:22433512

Stevens, Daniel S.; Crudder, Christopher H.; Domingo, Gonzalo J.

2012-01-01

261

Reverse transcriptase directs viral evolution in a deep ocean methane seep  

NASA Astrophysics Data System (ADS)

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.

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

2013-12-01

262

What are bloodborne pathogens? Bloodborne pathogens are infectious materials  

E-print Network

available Hepatitis B vaccinations to all employees with occupational exposure to bloodborne pathogens receive regular training that covers the dangers of bloodborne pathogens, preventive practices, and post

Pawlowski, Wojtek

263

Bacterial, Fungal, Parasitic, and Viral Myositis  

PubMed Central

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

Crum-Cianflone, Nancy F.

2008-01-01

264

[Viral hemorrhagic fevers as a biological weapon].  

PubMed

Viral haemorrhagic fevers are zoonoses caused by a group of phylogenetically diverse RNA-viruses, capable of causing serious haemorrhagic complications in humans. The West-African Ebola and Marburg viruses pose the most significant threat because of their easy spreading through direct contact with the ill person and high death rate reaching 90%. They are considered among the most dangerous agents possibly used in bioterrorist attack and have been studied as a part of the Soviet biological weapons programme. The first symptoms of the Ebola haemorrhagic fever appear 4 to 16 days after the infection and are rather unspecific (fever, flu-like and gastrointestinal symptoms, cough, sore throat, conjunctivitis). Within a few days the disease leads to weight loss, haemorrhagic complications and circulatory insufficiency. The infection may be transmitted through direct contact with the patient, his/her body fluids and cadavers; droplet transmission is much less likely. There is no specific prophylaxis nor treatment; still, isolation of patients and use of personal protection means by persons providing care to patients seem efficient in stopping the infection. The knowledge of the biology and epidemiology of Filoviridae is still limited, which makes the results of bioterrorist attack using these pathogens hard to predict. PMID:12728677

Grygorczuk, Sambor; Hermanowska-Szpakowicz, Teresa

2003-02-01

265

Sequencing Needs for Viral Diagnostics  

Microsoft Academic Search

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

Shea N. Gardner; Marisa W. Lam; Nisha J. Mulakken; Clinton L. Torres; Jason R. Smith; Tom R. Slezak

2004-01-01

266

VIRAL EVOLUTION Genomic surveillance elucidates  

E-print Network

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

Napp, Nils

267

Nosocomial Spread of Viral Disease  

PubMed Central

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

Aitken, Celia; Jeffries, Donald J.

2001-01-01

268

Method of Inhibiting Viral Production.  

National Technical Information Service (NTIS)

Viruses produce a series of antigens upon infection of a given cell. These antigens can be subdivided into two major categories, latent and lytic. Latent antigens are viral antigens not directly associated with the replication cycle of the virus, but in t...

I. Magrath, W. Soldschmidts

1990-01-01

269

Viral exanthems in the tropics  

Microsoft Academic Search

Viral exanthems are a common problem in tropical regions, particularly affecting children. Most exanthems are transient and harmless, but some are potentially very dangerous. Pregnant women and malnourished or immunocompromised infants carry the greatest risk of adverse outcome. In this article, parvovirus B19; dengue and yellow fever; West Nile, Barmah Forest, Marburg, and Ebola viruses, and human herpesviruses; asymmetric periflexural

Sueli Coelho da Silva Carneiro; Tania Cestari; Samuel H. Allen; Marcia Ramos e-Silva

2007-01-01

270

Maternal immunization against viral disease  

Microsoft Academic Search

The protective effect of maternal antibody against many viral diseases has been recognized. The use of maternal immunization has been considered as a means to augment this protection in the young infant against disease. Advantages of maternal immunization include the fact that young infants are most susceptible to infections but least responsive to vaccines, that pregnant women are accessible to

Janet Englund; W. Paul Glezen; Pedro A. Piedra

1998-01-01

271

Nucleic Acid Transport in Plant-Pathogen Interactions  

Microsoft Academic Search

\\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

Robert Lartey; Vitaly Citovsky

272

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

PubMed

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

Rustagi, Arjun; Gale, Michael

2014-03-20

273

Emerging roles of pathogens in Alzheimer disease.  

PubMed

Chronic spirochetal infection can cause slowly progressive dementia, cortical atrophy and amyloid deposition in the atrophic form of general paresis. There is a significant association between Alzheimer disease (AD) and various types of spirochete (including the periodontal pathogen Treponemas and Borrelia burgdorferi), and other pathogens such as Chlamydophyla pneumoniae and herpes simplex virus type-1 (HSV-1). Exposure of mammalian neuronal and glial cells and organotypic cultures to spirochetes reproduces the biological and pathological hallmarks of AD. Senile-plaque-like beta amyloid (A?) deposits are also observed in mice following inhalation of C. pneumoniae in vivo, and A? accumulation and phosphorylation of tau is induced in neurons by HSV-1 in vitro and in vivo. Specific bacterial ligands, and bacterial and viral DNA and RNA all increase the expression of proinflammatory molecules, which activates the innate and adaptive immune systems. Evasion of pathogens from destruction by the host immune reactions leads to persistent infection, chronic inflammation, neuronal destruction and A? deposition. A? has been shown to be a pore-forming antimicrobial peptide, indicating that A? accumulation might be a response to infection. Global attention and action is needed to support this emerging field of research because dementia might be prevented by combined antibiotic, antiviral and anti-inflammatory therapy. PMID:21933454

Miklossy, Judith

2011-01-01

274

RNA virus quasispecies: significance for viral disease and epidemiology.  

PubMed

The experimental evidence available for animal and plant RNA viruses, as well as other RNA genetic elements (viroids, satellites, retroelements, etc.), reinforces the view that many different types of genetic alterations may occur during RNA genome replication. This is fundamentally because of infidelity of genome replication and large population sizes. Homologous and heterologous recombination, as well as gene reassortments occur frequently during replication of retroviruses and most riboviruses, especially those that use enzymes with limited processivity. Following the generation of variant genomes, selection, which is dependent on environmental parameters in ways that are poorly understood, sorts out those genome fits enough to generate viable quasispecies. Chance events can also be destabilizing, as illustrated by recent results on fitness loss and other phenotypic changes accompanying bottleneck transmission. Variation, selection, and random sampling of genomes occur continuously and unavoidably during virus evolution. Evolution of RNA viruses is largely unpredictable because of the stochastic nature of mutation and recombination events, as well as the subtle effects of chance transmission events and host/environmental factors. Among environmental factors, alterations resulting from human intervention (deforestation, agricultural activities, global climatic changes, etc.) may alter dispersal patterns and provide new adaptive possibilities to viral quasispecies. Current understanding of RNA virus evolution suggests several strategies to control and diagnose viral diseases. The new generation of chemically defined vaccines and diagnostic reagents (monoclonal antibodies, peptide antigens, oligonucleotides for polymerase chain reaction amplification, etc.) may be adequate to prevent disease and detect some or even most of the circulating quasispecies of any given RNA pathogen. However, the dynamics of viral quasispecies mandate careful consideration of those reagents to be incorporated into diagnostic kits. Broadening diagnosis without jeopardizing specificity of detection will be challenging. There is a finite probability (impossible to quantify at present) that a defined vaccine may promote selection of escape mutants or a particular diagnostic kit may fail to detect a viral pathogen. Of particular concern are the potential long-term effects of weak selective pressures that may initially go unnoticed. Variant viruses resulting from evolutionary pressure imposed by vaccines or drugs may insidiously and gradually replace previous quasispecies. The great potential for variation and phenotypic diversity of some important RNA virus pathogens (human immunodeficiency virus, the hepatitis viruses, the newly recognized human hantaviruses, etc.) has become clear. Prevention and therapy should rely on multicomponent vaccines and antiviral agents to address the complexity of RNA quasispecies mutant spectra.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7827789

Duarte, E A; Novella, I S; Weaver, S C; Domingo, E; Wain-Hobson, S; Clarke, D K; Moya, A; Elena, S F; de la Torre, J C; Holland, J J

1994-08-01

275

RNA silencing suppression by plant pathogens: defence, counter-defence and counter-counter-defence.  

PubMed

RNA silencing is a central regulator of gene expression in most eukaryotes and acts both at the transcriptional level through DNA methylation and at the post-transcriptional level through direct mRNA interference mediated by small RNAs. In plants and invertebrates, the same pathways also function directly in host defence against viruses by targeting viral RNA for degradation. Successful viruses have consequently evolved diverse mechanisms to avoid silencing, most notably through the expression of viral suppressors of RNA silencing. RNA silencing suppressors have also been recently identified in plant pathogenic bacteria and oomycetes, suggesting that disruption of host silencing is a general virulence strategy across several kingdoms of plant pathogens. There is also increasing evidence that plants have evolved specific defences against RNA-silencing suppression by pathogens, providing yet another illustration of the never-ending molecular arms race between plant pathogens and their hosts. PMID:24129510

Pumplin, Nathan; Voinnet, Olivier

2013-11-01

276

Elevated Th17 response in infants undergoing respiratory viral infection.  

PubMed

IL-17 and T-helper (Th)17 cells contribute to viral airway pathology in human newborns. Because umbilical cord blood T cells fail to differentiate toward the Th17 lineage in the presence of autologous antigen-presenting cells, we asked whether Th17 cells are present in young infants that experience respiratory viral infection. To this end, we analyzed tracheal aspirate samples from infant patients suffering from acute respiratory syncytial virus (RSV) infection and healthy infant controls. Acute RSV infection associates with elevated IL-17 and accumulation of CD161(+) T cells in acute RSV infected lungs. Correspondingly, local Th17 polarizing cytokines were increased. In peripheral blood, we show that Th17 cells are absent in healthy 1-month-old infants, but are present in acute RSV patients. The triggering of pathogen-associated pattern receptors TLR4 and TLR7 promotes the generation of a Th17-polarizing cytokine environment by 1-month-old infant dendritic cell (DC). We thus conclude that although Th17 cells are absent in healthy newborns, Th17 cells are present in peripheral blood and the airways of infants that experience viral infection, thereby contributing to airway immunopathology. PMID:24650560

Stoppelenburg, Arie J; de Roock, Sytze; Hennus, Marije P; Bont, Louis; Boes, Marianne

2014-05-01

277

ISG15 Regulates Peritoneal Macrophages Functionality against Viral Infection  

PubMed Central

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

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

2013-01-01

278

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

Microsoft Academic Search

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

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

279

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

E-print Network

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

Shamos, Michael I.

280

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

PubMed Central

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

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

2012-01-01

281

Human Pathogen Importation Importing "Human" Pathogens from Outside Canada  

E-print Network

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

282

Enterovirus 71 Protease 2Apro Targets MAVS to Inhibit Anti-Viral Type I Interferon Responses  

PubMed Central

Enterovirus 71 (EV71) is the major causative pathogen of hand, foot, and mouth disease (HFMD). Its pathogenicity is not fully understood, but innate immune evasion is likely a key factor. Strategies to circumvent the initiation and effector phases of anti-viral innate immunity are well known; less well known is whether EV71 evades the signal transduction phase regulated by a sophisticated interplay of cellular and viral proteins. Here, we show that EV71 inhibits anti-viral type I interferon (IFN) responses by targeting the mitochondrial anti-viral signaling (MAVS) protein—a unique adaptor molecule activated upon retinoic acid induced gene-I (RIG-I) and melanoma differentiation associated gene (MDA-5) viral recognition receptor signaling—upstream of type I interferon production. MAVS was cleaved and released from mitochondria during EV71 infection. An in vitro cleavage assay demonstrated that the viral 2A protease (2Apro), but not the mutant 2Apro (2Apro-110) containing an inactivated catalytic site, cleaved MAVS. The Protease-Glo assay revealed that MAVS was cleaved at 3 residues between the proline-rich and transmembrane domains, and the resulting fragmentation effectively inactivated downstream signaling. In addition to MAVS cleavage, we found that EV71 infection also induced morphologic and functional changes to the mitochondria. The EV71 structural protein VP1 was detected on purified mitochondria, suggesting not only a novel role for mitochondria in the EV71 replication cycle but also an explanation of how EV71-derived 2Apro could approach MAVS. Taken together, our findings reveal a novel strategy employed by EV71 to escape host anti-viral innate immunity that complements the known EV71-mediated immune-evasion mechanisms. PMID:23555247

Wang, Bei; Xi, Xueyan; Lei, Xiaobo; Zhang, Xiaoyan; Cui, Sheng; Wang, Jianwei; Jin, Qi; Zhao, Zhendong

2013-01-01

283

Autistic disorder and viral infections  

Microsoft Academic Search

Autistic disorder (autism) is a behaviorally defined developmental disorder with a wide range of behaviors. Although the etiology\\u000a of autism is unknown, data suggest that autism results from multiple etiologies with both genetic and environmental contributions,\\u000a which may explain the spectrum of behaviors seen in this disorder. One proposed etiology for autism is viral infection very\\u000a early in development. The

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

2005-01-01

284

Viral exanthems in the tropics.  

PubMed

Viral exanthems are a common problem in tropical regions, particularly affecting children. Most exanthems are transient and harmless, but some are potentially very dangerous. Pregnant women and malnourished or immunocompromised infants carry the greatest risk of adverse outcome. In this article, parvovirus B19; dengue and yellow fever; West Nile, Barmah Forest, Marburg, and Ebola viruses, and human herpesviruses; asymmetric periflexural exanthema of childhood; measles; rubella; enteroviruses; Lassa fever; and South American hemorrhagic fevers will be discussed. PMID:17350501

Carneiro, Sueli Coelho da Silva; Cestari, Tania; Allen, Samuel H; Ramos e-Silva, Marcia

2007-01-01

285

[Emergence of "new" viral zoonoses].  

PubMed

In the last two to three decades a significant increase of viral zoonotic infections was observed. These zoonoses are not only newly (or previously unrecognized) emerging diseases, but also due to the reappearance of diseases thought to have been defeated (re-emerging diseases). "New" viral diseases can arise when viruses broaden their host-range (monkey poxvirus; equine morbillivirus), or can be a consequence of intrinsic properties of the virus itself, such as high mutation rates (influenza A virus). Most new or reemerging viral zoonoses are due to infections with hemorrhagic viruses. Many of them are transmitted by insects (arboviruses, e.g. yellow fever virus) or by rodents (e.g. Hanta viruses), others by contact with patients and nosocomial infections (e.g. Ebola virus). The emergence and increase of these diseases are a consequence of anthropogenic environmental changes, such as distortions of the ecological balance and changes in agriculture. In addition, the uncontrolled growth of the cities in tropical and subtropical regions without improvement of the public health measures and the increasing international animal trade and travel also favour the spread and recurrence of these diseases. PMID:10488638

Greiser-Wilke, I; Haas, L

1999-08-01

286

Molecular Engineering of Viral Gene Delivery Vehicles  

PubMed Central

Viruses can be engineered to efficiently deliver exogenous genes, but their natural gene delivery properties often fail to meet human therapeutic needs. Therefore, engineering viral vectors with new properties, including enhanced targeting abilities and resistance to immune responses, is a growing area of research. This review discusses protein engineering approaches to generate viral vectors with novel gene delivery capabilities. Rational design of viral vectors has yielded successful advances in vitro, and to an extent in vivo. However, there is often insufficient knowledge of viral structure-function relationships to reengineer existing functions or create new capabilities, such as virus-cell interactions, whose molecular basis is distributed throughout the primary sequence of the viral proteins. Therefore, high-throughput library and directed evolution methods offer alternative approaches to engineer viral vectors with desired properties. Parallel and integrated efforts in rational and library-based design promise to aid the translation of engineered viral vectors toward the clinic. PMID:18647114

Schaffer, David V.; Koerber, James T.; Lim, Kwang-il

2009-01-01

287

Evolution of microbial pathogens.  

PubMed Central

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

Morschhauser, J; Kohler, G; Ziebuhr, W; Blum-Oehler, G; Dobrindt, U; Hacker, J

2000-01-01

288

Persistence of Highly Pathogenic Avian Influenza Viruses in Natural Ecosystems  

PubMed Central

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

Feare, Chris J.; Renaud, Francois; Thomas, Frederic; Gauthier-Clerc, Michel

2010-01-01

289

Optimization and clinical validation of a pathogen detection microarray  

PubMed Central

DNA microarrays used as 'genomic sensors' have great potential in clinical diagnostics. Biases inherent in random PCR-amplification, cross-hybridization effects, and inadequate microarray analysis, however, limit detection sensitivity and specificity. Here, we have studied the relationships between viral amplification efficiency, hybridization signal, and target-probe annealing specificity using a customized microarray platform. Novel features of this platform include the development of a robust algorithm that accurately predicts PCR bias during DNA amplification and can be used to improve PCR primer design, as well as a powerful statistical concept for inferring pathogen identity from probe recognition signatures. Compared to real-time PCR, the microarray platform identified pathogens with 94% accuracy (76% sensitivity and 100% specificity) in a panel of 36 patient specimens. Our findings show that microarrays can be used for the robust and accurate diagnosis of pathogens, and further substantiate the use of microarray technology in clinical diagnostics. PMID:17531104

Wong, Christopher W; Heng, Charlie Lee Wah; Wan Yee, Leong; Soh, Shirlena WL; Kartasasmita, Cissy B; Simoes, Eric AF; Hibberd, Martin L; Sung, Wing-Kin; Miller, Lance D

2007-01-01

290

Uncovering Viral Protein-Protein Interactions and their Role in Arenavirus Life Cycle  

PubMed Central

The Arenaviridae family includes widely distributed pathogens that cause severe hemorrhagic fever in humans. Replication and packaging of their single-stranded RNA genome involve RNA recognition by viral proteins and a number of key protein-protein interactions. Viral RNA synthesis is directed by the virus-encoded RNA dependent-RNA polymerase (L protein) and requires viral RNA encapsidation by the Nucleoprotein. In addition to the role that the interaction between L and the Nucleoprotein may have in the replication process, polymerase activity appears to be modulated by the association between L and the small multifunctional Z protein. Z is also a structural component of the virions that plays an essential role in viral morphogenesis. Indeed, interaction of the Z protein with the Nucleoprotein is critical for genome packaging. Furthermore, current evidence suggests that binding between Z and the viral envelope glycoprotein complex is required for virion infectivity, and that Z homo-oligomerization is an essential step for particle assembly and budding. Efforts to understand the molecular basis of arenavirus life cycle have revealed important details on these viral protein-protein interactions that will be reviewed in this article. PMID:23170177

Loureiro, Maria Eugenia; D'Antuono, Alejandra; Levingston Macleod, Jesica M.; Lopez, Nora

2012-01-01

291

Viral-templated Palladium Nanocatalysts  

NASA Astrophysics Data System (ADS)

Despite recent progress on nanocatalysis, there exist several critical challenges in simple and readily controllable nanocatalyst synthesis including the unpredictable particle growth, deactivation of catalytic activity, cumbersome catalyst recovery and lack of in-situ reaction monitoring. In this dissertation, two novel approaches are presented for the fabrication of viral-templated palladium (Pd) nanocatalysts, and their catalytic activities for dichromate reduction reaction and Suzuki Coupling reaction were thoroughly studied. In the first approach, viral template based bottom-up assembly is employed for the Pd nanocatalyst synthesis in a chip-based format. Specifically, genetically displayed cysteine residues on each coat protein of Tobacco Mosaic Virus (TMV) templates provide precisely spaced thiol functionalities for readily controllable surface assembly and enhanced formation of catalytically active Pd nanoparticles. Catalysts with the chip-based format allow for simple separation and in-situ monitoring of the reaction extent. Thorough examination of synthesis-structure-activity relationship of Pd nanoparticles formed on surface-assembled viral templates shows that Pd nanoparticle size, catalyst loading density and catalytic activity of viral-templated Pd nanocatalysts can be readily controlled simply by tuning the synthesis conditions. The viral-templated Pd nanocatalysts with optimized synthesis conditions are shown to have higher catalytic activity per unit Pd mass than the commercial Pd/C catalysts. Furthermore, tunable and selective surface assembly of TMV biotemplates is exploited to control the loading density and location of Pd nanocatalysts on solid substrates via preferential electroless deposition. In addition, the catalytic activities of surface-assembled TMV-templated Pd nanocatalysts were also investigated for the ligand-free Suzuki Coupling reaction under mild reaction conditions. The chip-based format enables simple catalyst separation and reuse as well as facile product recovery. Reaction condition studies show that the solvent ratio played an important role in the selectivity of the Suzuki reaction, and that a higher water/acetonitrile ratio significantly facilitated the cross-coupling pathway. Meanwhile, in-depth characterizations including Atomic Force Microscopy (AFM), Grazing Incidence Small Angle X-ray Scattering (GISAXS), Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) and X-ray Photoelectron Spectroscopy (XPS) were carried out for these chip-based viral-templated Pd nanocatalysts. In the second approach, catalytically active TMV-templated Pd nanoparticles are encapsulated in readily exploited polymeric microparticle formats. Specifically, small (1˜2 nm), uniform and highly crystalline palladium (Pd) nanoparticles are spontaneously formed along (TMV) biotemplates without external reducing agents. The as-prepared Pd-TMV complexes are integrated into the hybrid poly(ethylene glycol)(PEG)-based microparticles via replica molding (RM) technique in a simple, robust and highly reproducible manner. The Pd-TMV complex structure was characterized by Transmission Electron Microscopy (TEM). The hybrid Pd-TMV-PEG microparticles are examined to have high catalytic activity, recyclability and stability through dichromate reduction. Combined these findings represent a significant step toward simple, robust, scalable synthesis and fabrication of efficient biotemplate-supported Pd nanocatalysts in readily deployable polymeric formats with high capacity in a well-controlled manner. These two simple, robust and readily controllable approaches for the fabrication of viral-templated Pd nanocatalysts, in both chip-based and hydrogel-encapsulated formats, can be readily extended to a variety of other nano-bio hybrid material synthesis in other catalytic reaction systems.

Yang, Cuixian

292

Viral induction of site-specific chromosome damage.  

PubMed

The advent of advanced cell culture and cytogenetics techniques in the 1950s opened a new avenue for research on the pathogenic interactions between animal viruses and their hosts. Studies of many viruses revealed their ability to nonspecifically induce cytogenetic damage to their host cell's chromosomes. However, only three viruses, the oncogenic adenoviruses, herpes simplex virus (HSV) and human cytomegalovirus (HCMV), have been found to cause non-random, site-specific chromosomal damage. Adenovirus (Ad) type 12 induces fragility at four distinct loci (RNU1, RNU2, RN5S and PSU1) in many different types of human cells. A common feature of these loci is that they contain a repeated array of transcriptionally active genes encoding small structural RNAs. Site-specific induction of breaks also requires the virally encoded E1B protein of M(r) 55000 and the C-terminus of the cellular p53 protein. Analysis of the induction of damage by HSV and HCMV necessitates consideration of several factors, including the strain of virus used, the timing of infection, the type of cell used, and the multiplicity of infection. Both HSV strains 1 and 2 are cytotoxic, although the former seems to be more proficient at inducing damage. At early times post infection, HSV induces breaks and specific uncoiling of the centromeres of chromosomes 1, 9 and 16. This is followed at later times by a more complete severing of all of the chromosomes, termed pulverisation. Damage by HSV requires viral entry and de novo viral protein synthesis, with immediate early viral proteins responsible for the induction of breaks and uncoiling and early gene products (most likely nucleases) involved in the extensive pulverisation seen later. HCMV has been studied primarily in permissive human fibroblasts. Its ability to induce specific damage in chromosome 1 at two loci, 1q21 and 1q42, was only recently revealed as the cells must be in S-phase when they are infected for the breaks to be observed. In contrast to adenovirus and HSV, HCMV induction of specific breakage requires only viral entry into the cell and not de novo viral protein expression. This latter point may be a factor in its ability to cause damage in the developing fetal brain, where the most severe clinical manifestations of congenital infection are observed. PMID:12516060

Fortunato, Elizabeth A; Spector, Deborah H

2003-01-01

293

Pathogens: raft hijackers.  

PubMed

Throughout evolution, organisms have developed immune-surveillance networks to protect themselves from potential pathogens. At the cellular level, the signalling events that regulate these defensive responses take place in membrane rafts--dynamic microdomains that are enriched in cholesterol and glycosphingolipids--that facilitate many protein-protein and lipid-protein interactions at the cell surface. Pathogens have evolved many strategies to ensure their own survival and to evade the host immune system, in some cases by hijacking rafts. However, understanding the means by which pathogens exploit rafts might lead to new therapeutic strategies to prevent or alleviate certain infectious diseases, such as those caused by HIV-1 or Ebola virus. PMID:12876558

Mañes, Santos; del Real, Gustavo; Martínez-A, Carlos

2003-07-01

294

Neopolyploidy and pathogen resistance  

PubMed Central

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

Oswald, Benjamin P; Nuismer, Scott L

2007-01-01

295

Luteovirus: insights into pathogenicity.  

PubMed

Luteoviruses are economically important plant viruses, infecting almost all cereals throughout the world. Idiosyncrasies related to this virus group may be a strategic consequence of viral genome compression. However, many fundamental questions have yet to be resolved. This review summarizes selected findings covering molecular aspects of pathogenesis relating to plant-infecting RNA viruses in general, and luteoviruses in specific. These studies enhance our understanding of the replication structures and the virus infection pathways. PMID:25091739

Ali, Muhammad; Hameed, Shahid; Tahir, Muhammad

2014-11-01

296

Host-pathogen interaction in HIV infection  

PubMed Central

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

Chowdhury, Ankita; Silvestri, Guido

2013-01-01

297

Tickling the TLR7 to cure viral hepatitis  

PubMed Central

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

2014-01-01

298

The change of etiological agents and clinical signs of epidemic viral conjunctivitis over an 18-year period in southern Taiwan  

Microsoft Academic Search

Background Epidemic viral conjunctivitis is a highly contagious eye disease that occurs worldwide and is caused mainly by adenoviruses and enteroviruses. An 18-year analysis of the changes of pathogens and clinical signs in a subtropical and densely populated island presents certain special features. Methods We retrospectively analyzed the clinical information and laboratory records of the conjunctivitis patients with positive conjunctival

Cheng-Hsien Chang; Kuei-Hsiang Lin; Min-Muh Sheu; Wen-Loong Huang; Huei-Zu Wang; Chen-Wu Chen

2003-01-01

299

Emerging viral diseases of fish and shrimp  

PubMed Central

The rise of aquaculture has been one of the most profound changes in global food production of the past 100 years. Driven by population growth, rising demand for seafood and a levelling of production from capture fisheries, the practice of farming aquatic animals has expanded rapidly to become a major global industry. Aquaculture is now integral to the economies of many countries. It has provided employment and been a major driver of socio-economic development in poor rural and coastal communities, particularly in Asia, and has relieved pressure on the sustainability of the natural harvest from our rivers, lakes and oceans. However, the rapid growth of aquaculture has also been the source of anthropogenic change on a massive scale. Aquatic animals have been displaced from their natural environment, cultured in high density, exposed to environmental stress, provided artificial or unnatural feeds, and a prolific global trade has developed in both live aquatic animals and their products. At the same time, over-exploitation of fisheries and anthropogenic stress on aquatic ecosystems has placed pressure on wild fish populations. Not surprisingly, the consequence has been the emergence and spread of an increasing array of new diseases. This review examines the rise and characteristics of aquaculture, the major viral pathogens of fish and shrimp and their impacts, and the particular characteristics of disease emergence in an aquatic, rather than terrestrial, context. It also considers the potential for future disease emergence in aquatic animals as aquaculture continues to expand and faces the challenges presented by climate change. PMID:20409453

Walker, Peter J.; Winton, James R.

2010-01-01

300

A viral RNA structural element alters host recognition of nonself RNA.  

PubMed

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

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

2014-02-14

301

Molecular Epidemiology of Viral Hemorrhagic Septicemia Virus in the Great Lakes Region  

E-print Network

Viral hemorrhagic septicemia virus (VHSV) is considered by many nations and international organizations to be one of the most important viral pathogens of finfish (Office International des Epizooties 2007). For several decades following its initial characterization in the 1950s, VHSV was thought to be limited to Europe where it was regarded as an endemic pathogen of freshwater fish that was especially problematic for farmed rainbow trout, an introduced species (Wolf 1988; Smail 1999). Subsequently, it was shown that VHSV was present among many species of marine and anadromous fishes in both the Pacific and Atlantic Oceans where it has been associated with substantial mortality among both wild and cultured fish (Meyers and Winton 1995; Skall et al. 2005). Beginning in 2005, reports from the Great Lakes region indicated that VHSV had been isolated from fish that had experienced very large die-offs in the wild (Elsayed et al.

unknown authors

302

Genetic shift of env V3 loop viral sequences in patients with HIV-associated neurocognitive disorder during antiretroviral therapy.  

PubMed

The development of human immunodeficiency virus type 1 (HIV)-associated neurocognitive disorder (HAND) involves the adaptation of viral sequences coding for the V3 loop of the env protein. The plasma and cerebrospinal fluid (CSF) may contain viral populations from various cellular sources and with differing pathogenicity. Combination antiretroviral therapy (cART) may alter the relative abundance of these viral populations, leading to a genetic shift. We characterized plasma and CNS viral populations prior to and during cART and relate the findings to viral elimination kinetics and the clinical phenotype. Longitudinal plasma and CSF samples of five chronically infected HIV patients, four of whom had HAND, and one seroconverter were analyzed for V3 sequences by RT-PCR and sequence analysis. In the chronically infected patients, pre-cART plasma and CSF viral sequences were different irrespective of viral elimination kinetics and clinical phenotype. cART induced replacement of plasma viral populations in all subjects. CSF viral populations underwent a clear genetic shift in some patients but remained stable in others. This was not dependent on the presence of HAND. The genetic shift of CSF V3 sequences was absent in the two subjects whose CSF viral load initially increased during cART. In one patient, pre- and post-treatment CSF sequences were closely related to the post-treatment plasma sequences, suggesting a common cellular source. We found heterogeneous patterns of genetic compartmentalization and genetic shift over time. Although these did not closely match viral elimination kinetics and clinical phenotype, the results imply different patterns of the dynamics and relative contribution of compartment-specific virus populations in chronic HIV infection. PMID:24101298

Eggers, Christian; Müller, Oliver; Thordsen, Ingo; Schreiber, Michael; Methner, Axel

2013-12-01

303

Drug Sanctuaries, Low Steady State Viral Loads and Viral Blips.  

SciTech Connect

Patients on HAART for long periods of time obtain viral loads (VLs) below 50 copies/ml. Ultrasensitive VL assays show that some of these patients obtain a low steady state VL, while others continue to exhibit VL declines to below 5 copies/ml. Low steady states can be explained by two-compartment models that incorporate a drug sanctuary. Interestingly, when patients exhibit continued declines below 50 copies/ml the rate of decline has a half-life of {approx} 6 months, consistent with some estimates of the rate of latent cell decline. Some patients, despite having sustained undetectable VLs show periods of transient viremia (blips). I will present some statistical characterization of the blips observed in a set of 123 patients, suggesting that blips are generated largely by random processes, that blips tend to correspond to periods of a few weeks in which VLs are elevated, and that VL decay from the peak of a blip may have two-phases. Using new results suggesting that the viral burst size, N {approx} 5 x 10{sup 4}, we estimate the number of cells needed to produce a blip.

Perelson, Alan S.,; Callaway, D. (Duncan); Pomerantz, R. J. (Roger J.); Chen, H. Y.; Markowitz, M.; Ho, David D.; Di Mascio, M. (Michele)

2002-01-01

304

The contribution of molecular epidemiology to the understanding and control of viral diseases of salmonid aquaculture  

PubMed Central

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

2011-01-01

305

Use of specific-pathogen-free (SPF) rhesus macaques to better model oral pediatric cytomegalovirus infection  

PubMed Central

Congenital human cytomegalovirus (HCMV) infection can result in lifelong neurological deficits. Seronegative pregnant woman often acquire primary HCMV from clinically asymptomatic, but HCMV-shedding children. Potential age-related differences in viral and immune parameters of primary RhCMV infection were examined in an oral rhesus CMV infection model in specific pathogen free macaques. PMID:22620273

dela Pena, Myra Grace; Strelow, Lisa; Barry, Peter A.

2012-01-01

306

Life-History Responses to Pathogens in Tiger Salamander (Ambystoma tigrinum) Larvae  

E-print Network

Life-History Responses to Pathogens in Tiger Salamander (Ambystoma tigrinum) Larvae MATTHEW J in Arizona Tiger Salamanders (Ambystoma tigrinum nebulosum). Viral epidemics cause extreme mortality in natural populations and, thus, impose a strong selective force. We tested how exposure to ATV during

Storfer, Andrew

307

Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza  

PubMed Central

Background Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients. Methods Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient. Results Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-?, the chemotactic factors MIP-1?, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p < 0.05). Correlation studies demonstrated also the existence of a significant positive association between the levels of these mediators, evidencing that they are simultaneously regulated in response to the virus. Conclusions Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1. PMID:21880131

2011-01-01

308

Primate viral diseases in perspective.  

PubMed

The recent occurrence of fatal Herpesvirus simiae (B virus) infection in human subjects has again focused the attention of primatologists on this virus. B virus, however, is only one of a number of viral diseases that plays a role in primate colony management. This report is to emphasize to the primatologist a number of viruses other than H. simiae, with high morbidity and mortality rates, of importance for health management of nonhuman primate animal colonies. This concept is supported by the recent occurrence in colonies of nonhuman primates of simian hemorrhagic fever virus, SA8, herpesvirus, respiratory syncytial virus, encephalomyocarditis virus, Ebola virus, and simian immunodeficiency viruses. PMID:2174083

Kalter, S S; Heberling, R L

1990-01-01

309

Therapeutic options for diseases due to potential viral agents of bioterrorism.  

PubMed

The etiologic agents of smallpox and viral hemorrhagic fever have emerged as potential agents of bioterrorism due to their virulence, potential for human to human dissemination and limited strategies for treatment and prevention. Cidofovir has shown significant promise in animal models, and limited case reports in humans are encouraging. Ribavirin is the treatment of choice for certain hemorrhagic fever viral infections, but has no current application to Ebola and Marburg infections. Current vaccine strategies for smallpox are effective, but carry significant risk for complications. Licensed vaccines for hemorrhagic fever viruses are limited to yellow fever, but animal studies are promising. Genomic analysis of the viral pathogen and the animal model response to infection may provide valuable information enabling the development of novel treatment and prevention strategies. Current knowledge of these strategies is reviewed. PMID:12669378

Bronze, Michael S; Greenfield, Ronald A

2003-02-01

310

Rapid Detection of Pathogens  

Microsoft Academic Search

Pathogen identification is a crucial first defense against bioterrorism. A major emphasis of our national biodefense strategy is to establish fast, accurate and sensitive assays for diagnosis of infectious diseases agents. Such assays will ensure early and appropriate treatment of infected patients. Rapid diagnostics can also support infection control measures, which monitor and limit the spread of infectious diseases agents.

David Perlin

2005-01-01

311

Quality controls for bovine viral diarrhea virus-free IVF embryos  

Microsoft Academic Search

Introduction of bovine viral diarrhea virus (BVDV) with cumulus-oocyte-complexes (COCs) from the abattoir is a concern in the production of bovine embryos in vitro. Further, International Embryo Transfer Society (IETS) guidelines for washing and trypsin treatment of invivo-derived bovine embryos ensure freedom from a variety of pathogens, but these procedures appear to be less effective when applied to IVF embryos.

D. A. Stringfellow; K. P. Riddell; P. K. Galik; P. Damiani; M. D. Bishop; J. C. Wright

2000-01-01

312

Bovine viral diarrhea virus: Its effects on estradiol, progesterone and prostaglandin secretion in the cow  

Microsoft Academic Search

Bovine viral diarrhea virus (BVDV) is a major cattle pathogen responsible for a spectrum of symptoms, including reproductive failure. This study was designed to establish the effects of BVDV infection on estradiol, progesterone and PGF2alpha secretion in the cow. Seven BVDV-free cows were challenged with non-cytopathogenic BVDV (strain Pe 515: 5sx106tissue culture infected dose50) so that peak viremia occurred during

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

1999-01-01

313

The contribution of molecular epidemiology to the understanding and control of viral diseases of salmonid aquaculture  

Microsoft Academic Search

Molecular epidemiology is a science which utilizes molecular biology to define the distribution of disease in a population\\u000a (descriptive epidemiology) and relies heavily on integration of traditional (or analytical) epidemiological approaches to\\u000a identify the etiological determinants of this distribution. The study of viral pathogens of aquaculture has provided many\\u000a exciting opportunities to apply such tools. This review considers the extent

Michael Snow

2011-01-01

314

Viral Factors Determine Progression to AIDS in Simian Immunodeficiency Virus-Infected Newborn Rhesus Macaques  

Microsoft Academic Search

To evaluate how viral variants may affect disease progression in human pediatric AIDS, we studied the potential of three simian immunodeficiency virus (SIV) isolates to induce simian AIDS in newborn rhesus macaques. The three virus isolates were previously shown to range from pathogenic (SIVmac251 and SIV- mac239) to nonpathogenic (SIVmac1A11) when inoculated intravenously into juvenile and adult rhesus macaques.Sixnewbornmacaquesinoculatedwithpathogenic,unclonedSIVmac251developedpersistent,high levelsofcell-associatedandcell-freeviremia,hadnodetectableantiviralantibodies,andhadpoorweightgain;

MARTA L. MARTHAS; KOEN K. A. VAN ROMPAY; MOSES OTSYULA; CHRISTOPHER J. MILLER; DON R. CANFIELD; NIELS C. PEDERSEN; ANDMICHAEL B. MCCHESNEY

1995-01-01

315

Pathogen-like particles: biomimetic vaccine carriers engineered at the nanoscale.  

PubMed

Vaccine adjuvants are an essential component of vaccine design, helping to generate immunity to pathogen antigens in the absence of infection. Recent advances in nanoscale engineering have created a new class of particulate bionanotechnology that uses biomimicry to better integrate adjuvant and antigen. These pathogen-like particles, or PLPs, can come from a variety of sources, ranging from fully synthetic platforms to biologically derived, self-assembling systems. By employing molecularly engineered targeting and stimulation of key immune cells, recent studies utilizing PLPs as vaccine delivery platforms have shown great promise against high-impact, unsolved vaccine targets ranging from bacterial and viral pathogens to cancer and addiction. PMID:24832075

Rosenthal, Joseph A; Chen, Linxiao; Baker, Jenny L; Putnam, David; DeLisa, Matthew P

2014-08-01

316

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

PubMed Central

The human respiratory tract is heavily exposed to microorganisms. Viral respiratory tract pathogens, like RSV, influenza and rhinoviruses cause major morbidity and mortality from respiratory tract disease. Furthermore, as viruses have limited means of transmission, viruses that cause pathogenicity in other tissues may be transmitted through the respiratory tract. It is therefore important to chart the human virome in this compartment. We have studied nasopharyngeal aspirate samples submitted to the Karolinska University Laboratory, Stockholm, Sweden from March 2004 to May 2005 for diagnosis of respiratory tract infections. We have used a metagenomic sequencing strategy to characterize viruses, as this provides the most unbiased view of the samples. Virus enrichment followed by 454 sequencing resulted in totally 703,790 reads and 110,931 of these were found to be of viral origin by using an automated classification pipeline. The snapshot of the respiratory tract virome of these 210 patients revealed 39 species and many more strains of viruses. Most of the viral sequences were classified into one of three major families; Paramyxoviridae, Picornaviridae or Orthomyxoviridae. The study also identified one novel type of Rhinovirus C, and identified a number of previously undescribed viral genetic fragments of unknown origin. PMID:22355331

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

2012-01-01

317

Compartmentalization of the gut viral reservoir in HIV-1 infected patients  

PubMed Central

Background Recently there has been an increasing interest and appreciation for the gut as both a viral reservoir as well as an important host-pathogen interface in human immunodefiency virus type 1 (HIV-1) infection. The gut associated lymphoid tissue (GALT) is the largest lymphoid organ infected by HIV-1. In this study we examined if different HIV-1 quasispecies are found in different parts of the gut of HIV-1 infected individuals. Results Gut biopsies (esophagus, stomach, duodenum and colorectum) were obtained from eight HIV-1 infected preHAART (highly active antiretroviral therapy) patients. HIV-1 Nef and Reverse transcriptase (RT) encoding sequences were obtained through nested PCR amplification from DNA isolated from the gut biopsy tissues. The PCR fragments were cloned and sequenced. The resulting sequences were subjected to various phylogenetic analyses. Expression of the nef gene and viral RNA in the different gut tissues was determined using real-time RT-PCR. Phylogenetic analysis of the Nef protein-encoding region revealed compartmentalization of viral replication in the gut within patients. Viral diversity in both the Nef and RT encoding region varied in different parts of the gut. Moreover, increased nef gene expression (p < 0.05) and higher levels of viral genome were observed in the colorectum (p < 0.05). These differences could reflect an adaptation of HIV-1 to the various tissues. Conclusion Our results indicated that different HIV-1 quasispecies populate different parts of the gut, and that viral replication in the gut is compartmentalized. These observations underscore the importance of the gut as a host-pathogen interface in HIV-1 infection. PMID:18053211

van Marle, Guido; Gill, M John; Kolodka, Dione; McManus, Leah; Grant, Tannika; Church, Deirdre L

2007-01-01

318

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

PubMed Central

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

Perales-Linares, Renzo; Navas-Martin, Sonia

2013-01-01

319

Commercialization of veterinary viral vaccines.  

PubMed

If vaccines are to reliably prevent disease, they must be developed, produced and quality-controlled according to very strict regulations and procedures. Veterinary viral vaccine registrations are governed by different rules in different countries, but these rules all emphasize that the quality of the raw materials--the cells, eggs, animals or plants that are used in production--need to be carefully controlled. The veterinary vaccine business is also very cost-conscious. Emphasis over the last 5-10 years has therefore been to develop culture systems that minimize labor and sterility problems and thus provide for reliable and cost-effective production. Implementing these often more complex systems in a production environment takes considerable effort, first in scale-up trials and further down the line in convincing production personnel to change their familiar system for something new and possibly untried. To complete scale-up trials successfully, it is absolutely necessary to understand the biochemistry of the cells and the influence of the virus on the cells under scale-up and later production conditions. Once a viral product can be produced on a large scale, it is imperative that the quality of the end-product is controlled in an intelligent way. One needs to know whether the end-product performs in the animal as was intended during its conception in the research and development department. The development of the appropriate tests to demonstrate this plays an important role in the successful development of a vaccine. PMID:15984331

Flore, P H

2004-12-01

320

Sequencing needs for viral diagnostics.  

PubMed

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. Severe acute respiratory syndrome 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. PMID:15583268

Gardner, Shea N; Lam, Marisa W; Mulakken, Nisha J; Torres, Clinton L; Smith, Jason R; Slezak, Tom R

2004-12-01

321

Sequencing Needs for Viral Diagnostics  

SciTech Connect

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.

Gardner, S N; Lam, M; Mulakken, N J; Torres, C L; Smith, J R; Slezak, T

2004-01-26

322

Viral Advertising: Definitional Review and Synthesis  

Microsoft Academic Search

The objectives of this article are threefold. First, it provides an overview of the past published social media research focusing on different aspects of the viral communication, variously termed “electronic word-of-mouth,” “word-of-mouse,” “viral marketing,” and “buzz.” Second, it clarifies and analyzes the concept of viral advertising in social media. Third, it provides a definition to reduce the prevailing ambiguities in

Maria Petrescu; Pradeep Korgaonkar

2011-01-01

323

Viral security proteins: counteracting host defences  

Microsoft Academic Search

Interactions with host defences are key aspects of viral infection. Various viral proteins perform counter-defensive functions, but a distinct class, called security proteins, is dedicated specifically to counteracting host defences. Here, the properties of the picornavirus security proteins L and 2A are discussed. These proteins have well-defined positions in the viral polyprotein, flanking the capsid precursor, but they are structurally

Anatoly P. Gmyl; Vadim I. Agol

2010-01-01

324

Viral Load Monitoring in HIV Infection.  

PubMed

Measurement of HIV-1 viral load is now an accepted part of clinical practice for the determination of clinical prognosis and antiretroviral effectiveness in HIV infection. Consensus guidelines have been published on the appropriate use of this testing. Furthermore, recent advances in molecular technology have improved the sensitivity and reproducibility of viral load assays, and these improved assays have provided new insight into the pathogenesis of HIV disease. This article reviews new issues affecting viral load quantification, including viral subtypes, sex, compartmental differences, and other covariables. PMID:11095829

Holodniy

1999-12-01

325

Did viral disease of humans wipe out the Neandertals?  

PubMed

Neandertals were an anatomically distinct hominoid species inhabiting a vast geographical area ranging from Portugal to western Siberia and from northern Europe to the Middle East. The species became extinct 28,000 years ago, coinciding with the arrival of anatomically modern humans (AMHs) in Europe 40,000 years ago. There has been considerable debate surrounding the main causes of the extinction of Neandertals. After at least 200,000 years of successful adaption to the climate, flora and fauna of Eurasia, it is not clear why they suddenly failed to survive. For many years, climate change or competition with anatomically modern human (AMH) have been the leading hypotheses. Recently these hypotheses have somewhat fallen out of favour due to the recognition that Neandertals were a highly developed species with complex social structure, culture and technical skills. Were AMHs lucky and survived some catastrophe that eradicated the Neandertals? It seems unlikely that this is the case considering the close timing of the arrival of AMHs and the disappearance of Neandertals. Perhaps the arrival of AMHs also brought additional new non-human microscopic inhabitants to the regions where Neandertals lived and these new inhabitants contributed to the disappearance of the species. We introduce a medical hypothesis that complements other recent explanations for the extinction of Neandertals. After the ancestors of Neandertals left Africa, their immune system adapted gradually to the pathogens in their new Eurasian environment. In contrast, AMHs continued to co-evolve with east African pathogens. More than 200,000 years later, AMHs carried pathogens that would have been alien to pre-historic Europe. First contact between long separated populations can be devastating. Recent European and American history provides evidence for similar events, where introduction of viral, protozoan or bacterial pathogens to immunologically naïve populations lead to mass mortality and local population extinction. We propose that a virus, possibly from the family Herpesviridae, contributed to Neandertal extinction. PMID:20172660

Wolff, Horst; Greenwood, Alex D

2010-07-01

326

Universal extraction method for gastrointestinal pathogens.  

PubMed

A universal stool extraction method for recovery of nucleic acids (NAs) from gastrointestinal pathogens was developed to support rapid diagnostics for the London 2012 Olympics. The method involved mechanical disruption (bead beating) of the stools, followed by automated extraction and detection using real-time PCR. This method had been used extensively in the Second Infectious Intestinal Disease Study (IID2) for the isolation of NA from bacteria and parasites (and was effective for the robust recovery of Cryptosporidium spp.) but had not been used for enteric viruses. To ensure this method was universally suitable, panels of samples known to contain target bacteria, viruses or parasites were processed in triplicate using the pre-treatment method routinely used for each target and the new extraction method (bead beating). The extracts were tested using real-time PCR and the cycle threshold values were compared. The results from this study showed that bead beating improved yields for the bacterial and parasitic targets and was suitable for the viral targets. The implementation of this universal method should confer cost- and time-saving benefits and streamline the processes required for the characterization of an array of pathogens from faecal samples. PMID:23831766

Halstead, Fenella D; Lee, Adele V; Couto-Parada, Xose; Polley, Spencer D; Ling, Clare; Jenkins, Claire; Chalmers, Rachel M; Elwin, Kristin; Gray, Jim J; Iturriza-Gómara, Miren; Wain, John; Clark, Duncan A; Bolton, Frederick J; Manuel, Rohini J

2013-10-01

327

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...

328

Olive knot and its pathogens  

Microsoft Academic Search

Olive knot, caused by a pathogen or pathogens within the group of bacterial pathogens currently known as Pseudomonas savastanoi, is described. The ecology, transmission and methods of control of the pathogens are discussed. Strategies to minimise the\\u000a effects of infection are recommended and these depend on attention to specific details in programs for pruning, irrigation\\u000a and use of fertiliser. Introduction

J. M. Young

2004-01-01

329

Multiplex detection of agricultural pathogens  

DOEpatents

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.

Siezak, Thomas R.; Gardner, Shea; Torres, Clinton; Vitalis, Elizabeth; Lenhoff, Raymond J.

2013-01-15

330

Hantaviruses in the Americas and Their Role as Emerging Pathogens  

PubMed Central

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

Hjelle, Brian; Torres-Perez, Fernando

2010-01-01

331

Chitosan against cutaneous pathogens.  

PubMed

Propionibacterium acnes and Staphylococcus aureus are cutaneous pathogens that have become increasingly resistant to antibiotics. We sought to determine if chitosan, a polymer of deacetylated chitin, could be used as a potential treatment against these bacteria. We found that higher molecular weight chitosan had superior antimicrobial properties compared to lower molecular weights, and that this activity occurred in a pH dependent manner. Electron and fluorescence microscopy revealed that chitosan forms aggregates and binds to the surface of bacteria, causing shrinkage of the bacterial membrane from the cell wall. Of special relevance, clinical isolates of P. acnes were vulnerable to chitosan, which could be combined with benzoyl peroxide for additive antibacterial effect. Chitosan also demonstrated significantly less cytotoxicity to monocytes than benzoyl peroxide. Overall, chitosan demonstrates many promising qualities for treatment of cutaneous pathogens. PMID:23829873

Champer, Jackson; Patel, Julie; Fernando, Nathalie; Salehi, Elaheh; Wong, Victoria; Kim, Jenny

2013-01-01

332

Effect of bovine viral diarrhea virus in the feedlot.  

PubMed

It could be argued that bovine viral diarrhea virus (BVDV) is one of the most economically significant infectious pathogens of feedlot cattle. Although the direct economic losses caused by this virus have not been well quantified, the role it plays as an immunosuppressive agent and as a potentiator for other diseases, most notably bovine respiratory disease, have been well documented. It is also a difficult disease for the feedlot veterinarian to control effectively. Individual cattle persistently infected with BVDV often serve as the source of infectious virus within a group of feedlot cattle, and the ultimate responsibility for preventing persistent infections in cattle rests with the cow-calf producer and not with the feedlot owner. The enormous impact of the virus on the livestock industry has led the Academy of Veterinary Consultants to draft a position statement that resolves that the beef and dairy industries adopt measures to control and target eventual eradication of BVDV from North America. PMID:15062473

Campbell, John R

2004-03-01

333

New Insights into IDO Biology in Bacterial and Viral Infections  

PubMed Central

Initially, indoleamine-2,3-dioxygenase (IDO) has been introduced as a bactericidal effector mechanism and has been linked to T-cell immunosuppression and tolerance. In recent years, evidence has been accumulated that IDO also plays an important role during viral infections including HIV, influenza, and hepatitis B and C. Moreover, novel aspects about the role of IDO in bacterial infections and sepsis have been revealed. Here, we review these recent findings highlighting the central role of IDO and tryptophan metabolism in many major human infections. Moreover, we also shed light on issues concerning human-specific and mouse-specific host–pathogen interactions that need to be considered when studying the biology of IDO in the context of infections. PMID:25157255

Schmidt, Susanne V.; Schultze, Joachim L.

2014-01-01

334

(Mechanisms of inhibition of viral replication in plants)  

SciTech Connect

During the last year we have made a number of important observations in the fields of virology and plant molecular biology. By directly sequencing Tomato Mosaic Virus (ToMV) movement genes, previously undetected sequence alterations common to specific viral strains were found. The difficulty in regenerating transgenic tomato plants containing the Tm-2 gene was overcome. Tobacco plants transformed with Cucumber Mosaic Virus (CMV) are being characterized. Analysis of transgenic tobacco plants expressing CMV coat protein have shown no correlation between coat protein expression and level of resistance. Specific amino acid changes have been found to correlate with CMV resistance breaking and degree of pathogenicity. Satellite RNAs are shown to be too unstable for use as a biological control agent. The aphid transmission domain CMV has been localized to one (or more) of three amino acids; constructs have been made to determine the exact amino acids involved. 15 refs.

Not Available

1991-01-01

335

Adhesion by Pathogenic Corynebacteria  

Microsoft Academic Search

\\u000a Pathogenic members of the genus Corynebacterium cause a wide range of serious infections in humans including diphtheria. Adhesion to host cells is a crucial step during\\u000a infection. In Corynebacterium diphtheriae, adhesion is mediated primarily by filamentous structures called pili or fimbriae that are covalently attached to the bacterial\\u000a cell wall. C. diphtheriae produces three distinct pilus structures, SpaA-, SpaD- and

Elizabeth A. Rogers; Asis Das; Hung Ton-That

336

Pathogenic agents in freshwater resources  

Microsoft Academic Search

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

Edwin E. Geldreich

1996-01-01

337

Viral vectors for veterinary vaccines.  

PubMed

Whatever strategy is adopted for the development of viral vectors for delivery of veterinary vaccines there are several key points to consider: (1) Will the vectored vaccine give a delivery advantage compared to what's already available? (2) Will the vectored vaccine give a manufacturing advantage compared to what's already available? (3) Will the vectored vaccine provide improved safety compared to what's already available? (5) Will the vectored vaccine increase the duration of immunity compared to what's already available? (6) Will the vectored vaccine be more convenient to store compared to what's already available? (7) Is the vectored vaccine compatible with other vaccines? If there is no other alternative available then the answer to these questions is easy. However, if there are alternative vaccines available then the answers to these questions become very important because the answers will determine whether a vectored vaccine is merely a good laboratory idea or a successful vaccine. PMID:9890015

Sheppard, M

1999-01-01

338

Viral modulation of programmed necrosis  

PubMed Central

Summary Apoptosis and programmed necrosis balance each other as alternate first line host defense pathways against which viruses have evolved countermeasures. Intrinsic apoptosis, the critical programmed cell death pathway that removes excess cells during embryonic development and tissue homeostasis, follows a caspase cascade triggered at mitochondria and modulated by virus-encoded anti-apoptotic B cell leukemia (BCL)2-like suppressors. Extrinsic apoptosis controlled by caspase 8 arose during evolution to trigger executioner caspases directly, circumventing viral suppressors of intrinsic (mitochondrial) apoptosis and providing the selective pressure for viruses to acquire caspase 8 suppressors. Programmed necrosis likely evolved most recently as a “trap door” adaptation to extrinsic apoptosis. Receptor interacting protein (RIP)3 kinase (also called RIPK3) becomes active when either caspase 8 activity or polyubiquitylation of RIP1 is compromised. This evolutionary dialogue implicates caspase 8 as “supersensor” alternatively activating and suppressing cell death pathways. PMID:23773332

Kaiser, William J.; Upton, Jason W.; Mocarski, Edward S.

2013-01-01

339

Viral diversity and clonal evolution from unphased genomic data  

PubMed Central

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.

2014-01-01

340

Stochastic effects are important in intrahost HIV evolution even when viral loads are high.  

PubMed

Blood plasma viral loads and the time to progress to AIDS differ widely among untreated HIV-infected humans. Although people with certain HLA (HLA-I) alleles are more likely to control HIV infections without therapy, the majority of such untreated individuals exhibit high viral loads and progress to AIDS. Stochastic effects are considered unimportant for evolutionary dynamics in HIV-infected people when viral load is high or when selective forces strongly drive mutation. We describe a computational study of host-pathogen interaction demonstrating that stochastic effects can have a profound influence on disease dynamics, even in cases of high viral load and strong selective pressure. These stochastic effects are pronounced when the virus must traverse a fitness "barrier" in sequence space to escape the host's cytotoxic T-lymphocyte (CTL) response, as often occurs when a fitness defect imposed by a CTL-driven mutation must be compensated for by other mutations. These "barrier-crossing" events are infrequent and stochastic, resulting in divergent disease outcomes in genetically identical individuals infected by the same viral strain. Our results reveal how genetic determinants of the CTL response control the probability with which an individual is able to control HIV infection indefinitely, and thus provide clues for vaccine design. PMID:23112156

Read, Elizabeth L; Tovo-Dwyer, Allison A; Chakraborty, Arup K

2012-11-27

341

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

PubMed

Nematodes are the most abundant multicellular animals on earth, yet little is known about their natural viral pathogens. To date, only two nematode virus genomes have been reported. Consequently, nematode viruses have been overlooked as important biotic factors in the study of nematode ecology. Here, we show that one plant parasitic nematode species, Heterodera glycines, the soybean cyst nematode (SCN), harbours four different RNA viruses. The nematode virus genomes were discovered in the SCN transcriptome after high-throughput sequencing and assembly. All four viruses have negative-sense RNA genomes, and are distantly related to nyaviruses and bornaviruses, rhabdoviruses, bunyaviruses and tenuiviruses. Some members of these families replicate in and are vectored by insects, and can cause significant diseases in animals and plants. The novel viral sequences were detected in both eggs and the second juvenile stage of SCN, suggesting that these viruses are transmitted vertically. While there was no evidence of integration of viral sequences into the nematode genome, we indeed detected transcripts from these viruses by using quantitative PCR. These data are the first finding of virus genomes in parasitic nematodes. This discovery highlights the need for further exploration for nematode viruses in all tropic groups of these diverse and abundant animals, to determine how the presence of these viruses affects the fitness of the nematode, strategies of viral transmission and mechanisms of viral pathogenesis. PMID:21490246

Bekal, Sadia; Domier, Leslie L; Niblack, Terry L; Lambert, Kris N

2011-08-01

342

Toll-like receptors in CNS viral infections.  

PubMed

Protection against viral infections is critically dependent upon the early production of significant levels of type 1 interferons and the expression of interferon-stimulated genes that function as the effectors of innate antiviral immunity. Activation of Toll-like receptors on cells of the immune system is known to play an important role in this process. In this chapter we review evidence for a role of TLRs in innate immune responses against viral infections of the central nervous system. By far the most extensive literature pertains to TLR3. Data from various laboratories have shown that TLR3 is expressed in cells endogenous to the CNS, particularly in astrocytes and microglia. Triggering TLR3 by synthetic dsRNA, poly I:C effectively induces innate antiviral responses as well as boosts adaptive immune responses. Additional experiments show cooperative responses between TLRs (3, 7/8 and 9) in mounting an effective antiviral immune response in the periphery. Perhaps the most exciting data are from patient populations that document the critical role that specific TLRs play in specific CNS infections. Studies also suggest that inappropriate activation of the TLRs can result in a pathogenic outcome rather than a protective one. Since TLR ligands are being actively considered for their antiviral and potential adjuvant effects, this will be an important issue to address in the context of the CNS environment. PMID:19688328

Suh, Hyeon-Sook; Brosnan, Celia F; Lee, Sunhee C

2009-01-01

343

Bovine viral diarrhea virus infection induces autophagy in MDBK cells.  

PubMed

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

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

2014-07-01

344

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

PubMed

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

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

2006-04-01

345

Production and Titering of Recombinant Adeno-associated Viral Vectors  

PubMed Central

In recent years recombinant adeno-associated viral vectors (AAV) have become increasingly valuable for in vivo studies in animals, and are also currently being tested in human clinical trials. Wild-type AAV is a non-pathogenic member of the parvoviridae family and inherently replication-deficient. The broad transduction profile, low immune response as well as the strong and persistent transgene expression achieved with these vectors has made them a popular and versatile tool for in vitro and in vivo gene delivery. rAAVs can be easily and cheaply produced in the laboratory and, based on their favourable safety profile, are generally given a low safety classification. Here, we describe a method for the production and titering of chimeric rAAVs containing the capsid proteins of both AAV1 and AAV2. The use of these so-called chimeric vectors combines the benefits of both parental serotypes such as high titres stocks (AAV1) and purification by affinity chromatography (AAV2). These AAV serotypes are the best studied of all AAV serotypes, and individually have a broad infectivity pattern. The chimeric vectors described here should have the infectious properties of AAV1 and AAV2 and can thus be expected to infect a large range of tissues, including neurons, skeletal muscle, pancreas, kidney among others. The method described here uses heparin column purification, a method believed to give a higher viral titer and cleaner viral preparation than other purification methods, such as centrifugation through a caesium chloride gradient. Additionally, we describe how these vectors can be quickly and easily titered to give accurate reading of the number of infectious particles produced. PMID:22143312

Wulff, Peer; Klugmann, Matthias; Murray, Andrew J.

2011-01-01

346

Viral respiratory infections in cystic fibrosis  

Microsoft Academic Search

Viral respiratory infections in CF patients are associated with an increase in morbidity at short and long term. Viral infections have a greater impact on CF patients compared to non-CF controls. They result in increased respiratory symptoms, deterioration of Shwachman and radiological scores, prolonged hospitalizations, a persistent decrease of pulmonary function, increased use of antibiotics and a higher frequency of

Bart E. van Ewijk; Marieke M. van der Zalm; Tom F. W. Wolfs; Cornelis K. van der Ent

2005-01-01

347

The Dynamics of Viral Marketing Jure Leskovec  

E-print Network

that successfully identifies product and pricing categories for which viral marketing seems to be very effective resistance to tradi- tional forms of advertising such as TV or newspaper ads, marketers have turned are natural candidates for viral marketing, because the product can be observed or advertised as part

Pratt, Vaughan

348

Preparation of viral DNA from nucleocapsids.  

PubMed

Viruses are obligate cellular parasites, and thus the study of their DNA requires isolating viral material away from host cell contaminants and DNA. Several downstream applications require large quantities of pure viral DNA, which is provided by this protocol. These applications include viral genome sequencing, where the removal of host DNA is crucial to optimize data output for viral sequences, and the production of new viral recombinant strains, where co-transfection of purified plasmid and linear viral DNA facilitates recombination.(1,2,3) This procedure utilizes a combination of extractions and density-based centrifugation to isolate purified linear herpesvirus nucleocapsid DNA from infected cells.(4,5) The initial purification steps aim to isolate purified viral capsids, which contain and protect the viral DNA during the extractions and centrifugation steps that remove cellular proteins and DNA. Lysis of nucleocapsids then releases viral DNA, and two final phenol-chloroform steps remove remaining proteins. The final DNA captured from solution is highly concentrated and pure, with an average OD(260/280;) of 1.90. Depending on the quantity of infected cells used, yields of viral DNA range from 150-800 ?g or more. The purity of this DNA makes it stable during long-term storage at 4C. This DNA is thus ideally suited for high-throughput sequencing, high fidelity PCR reactions, and transfections. Prior to beginning the protocol, it is important to know the average number of cells per dish (e.g. an average of 8 x 10(6) PK-15 cells in a confluent 15 cm dish), and the titer of the viral stock to be used (e.g. 1 x 10(8) plaque-forming units per ml). These are necessary to calculate the appropriate multiplicity of infection (MOI) for the protocol.(6) For instance, to infect one 15 cm dish of PK-15 cells with the above viral stock, at an MOI of 5, you would use 400 ?l of viral stock and dilute it with 3.6 ml of medium (total inoculation volume of 4 ml for one 15 cm plate). Multiple viral DNA preparations can be prepared at the same time. The number of simultaneous preparations is limited only by the number of tubes held by the ultracentrifuge rotor (one per virus; see step 3.9 below). Here we describe the procedure as though being done for one virus. PMID:21876519

Szpara, Moriah L; Tafuri, Yolanda R; Enquist, L W

2011-01-01

349

Reovirus ?NS Protein Is Required for Nucleation of Viral Assembly Complexes and Formation of Viral Inclusions  

PubMed Central

Progeny virions of mammalian reoviruses are assembled in the cytoplasm of infected cells at discrete sites termed viral inclusions. Studies of temperature-sensitive (ts) mutant viruses indicate that nonstructural protein ?NS and core protein ?2 are required for synthesis of double-stranded (ds) RNA, a process that occurs at sites of viral assembly. We used confocal immunofluorescence microscopy and ts mutant reoviruses to define the roles of ?NS and ?2 in viral inclusion formation. In cells infected with wild-type (wt) reovirus, ?NS and ?2 colocalize to large, perinuclear structures that correspond to viral inclusions. In cells infected at a nonpermissive temperature with ?NS-mutant virus tsE320, ?NS is distributed diffusely in the cytoplasm and ?2 is contained in small, punctate foci that do not resemble viral inclusions. In cells infected at a nonpermissive temperature with ?2-mutant virus tsH11.2, ?2 is distributed diffusely in the cytoplasm and the nucleus. However, ?NS localizes to discrete structures in the cytoplasm that contain other viral proteins and are morphologically indistinguishable from viral inclusions seen in cells infected with wt reovirus. Examination of cells infected with wt reovirus over a time course demonstrates that ?NS precedes ?2 in localization to viral inclusions. These findings suggest that viral RNA-protein complexes containing ?NS nucleate sites of viral replication to which other viral proteins, including ?2, are recruited to commence dsRNA synthesis. PMID:11152519

Becker, Michelle M.; Goral, Mehmet I.; Hazelton, Paul R.; Baer, Geoffrey S.; Rodgers, Steven E.; Brown, Earl G.; Coombs, Kevin M.; Dermody, Terence S.

2001-01-01

350

BK polyomavirus: emerging pathogen  

PubMed Central

BK polyomavirus (BKPyV) is a small double-stranded DNA virus that is an emerging pathogen in immunocompromised individuals. BKPyV is widespread in the general population, but primarily causes disease when immune suppression leads to reactivation of latent virus. Polyomavirus-associated nephropathy and hemorrhagic cystitis in renal and bone marrow transplant patients, respectively, are the most common diseases associated with BKPyV reactivation and lytic infection. In this review, we discuss the clinical relevance, effects on the host, virus life cycle, and current treatment protocols. PMID:22402031

Bennett, Shauna M.; Broekema, Nicole M.; Imperiale, Michael J.

2013-01-01

351

Host-Pathogen Interactions  

PubMed Central

A polysaccharide from the fungal pathogen Colletotrichum lindemuthianum causes browning and phytoalexin production when applied to the cut surfaces of bean (Phaseolus vulgaris) cotyledons and hypocotyls. The application of an amount of polysaccharide equivalent to less than 100 ng of glucose will elicit this response in the bean tissues. The polysaccharide has been isolated both from culture filtrates and from the mycelial walls of the fungus. Purification of the polysaccharide involved anion and cation exchange chromatography and gel filtration. The polysaccharide has an apparent molecular weight between 1,000,000 and 5,000,000 daltons, and consists predominantly of 3- and 4-linked glucosyl residues. PMID:16659289

Anderson-Prouty, Anne J.; Albersheim, Peter

1975-01-01

352

Viral and Bacterial Interactions in the Upper Respiratory Tract  

PubMed Central

Respiratory infectious diseases are mainly caused by viruses or bacteria that often interact with one another. Although their presence is a prerequisite for subsequent infections, viruses and bacteria may be present in the nasopharynx without causing any respiratory symptoms. The upper respiratory tract hosts a vast range of commensals and potential pathogenic bacteria, which form a complex microbial community. This community is assumed to be constantly subject to synergistic and competitive interspecies interactions. Disturbances in the equilibrium, for instance due to the acquisition of new bacteria or viruses, may lead to overgrowth and invasion. A better understanding of the dynamics between commensals and pathogens in the upper respiratory tract may provide better insight into the pathogenesis of respiratory diseases. Here we review the current knowledge regarding specific bacterial–bacterial and viral–bacterial interactions that occur in the upper respiratory niche, and discuss mechanisms by which these interactions might be mediated. Finally, we propose a theoretical model to summarize and illustrate these mechanisms. PMID:23326226

Bosch, Astrid A. T. M.; Biesbroek, Giske; Trzcinski, Krzysztof; Sanders, Elisabeth A. M.; Bogaert, Debby

2013-01-01

353

Human pathogenic bacteria, fungi, and viruses in Drosophila  

PubMed Central

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

Panayidou, Stavria; Ioannidou, Eleni; Apidianakis, Yiorgos

2014-01-01

354

Cryptosporidium Pathogenicity and Virulence  

PubMed Central

Cryptosporidium is a protozoan parasite of medical and veterinary importance that causes gastroenteritis in a variety of vertebrate hosts. Several studies have reported different degrees of pathogenicity and virulence among Cryptosporidium species and isolates of the same species as well as evidence of variation in host susceptibility to infection. The identification and validation of Cryptosporidium virulence factors have been hindered by the renowned difficulties pertaining to the in vitro culture and genetic manipulation of this parasite. Nevertheless, substantial progress has been made in identifying putative virulence factors for Cryptosporidium. This progress has been accelerated since the publication of the Cryptosporidium parvum and C. hominis genomes, with the characterization of over 25 putative virulence factors identified by using a variety of immunological and molecular techniques and which are proposed to be involved in aspects of host-pathogen interactions from adhesion and locomotion to invasion and proliferation. Progress has also been made in the contribution of host factors that are associated with variations in both the severity and risk of infection. Here we provide a review comprised of the current state of knowledge on Cryptosporidium infectivity, pathogenesis, and transmissibility in light of our contemporary understanding of microbial virulence. PMID:23297262

Bouzid, Maha; Chalmers, Rachel M.; Tyler, Kevin M.

2013-01-01

355

Host-Pathogen Interactions  

PubMed Central

An elicitor of glyceollin accumulation in soybeans (Glycine max L.) has been isolated from a commercially available extract of brewers' yeast. Yeast is not a known pathogen of plants. The elicitor was isolated by precipitation in 80% (v/v) ethanol followed by column chromatography on DEAE-cellulose, sulfopropyl-Sephadex, and concanavalin A-Sepharose. Compositional and structural analysis showed the elicitor to be a glucan containing terminal, 3-, 6-, and 3,6-linked glucosyl residues. The yeast elicitor stimulates the accumulation of glyceollin in the cotyledons and hypocotyls of soybeans when as little as 15 nanograms or 100 nanograms of the elicitor is applied to the respective tissues. The yeast elicitor is very similar in both structure and absolute elicitor activity to an elicitor isolated from the mycelial walls of Phytophthora megasperma var. sojae, a pathogen of soybeans. These and other results of this laboratory suggest that plants are able to respond to the presence of a wide range of fungi by recognizing, as foreign to the plant, structural polysaccharides of the mycelial walls of the fungi. PMID:16660446

Hahn, Michael G.; Albersheim, Peter

1978-01-01

356

Viral tagging reveals discrete populations in Synechococcus viral genome sequence space.  

PubMed

Microbes and their viruses drive myriad processes across ecosystems ranging from oceans and soils to bioreactors and humans. Despite this importance, microbial diversity is only now being mapped at scales relevant to nature, while the viral diversity associated with any particular host remains little researched. Here we quantify host-associated viral diversity using viral-tagged metagenomics, which links viruses to specific host cells for high-throughput screening and sequencing. In a single experiment, we screened 10(7) Pacific Ocean viruses against a single strain of Synechococcus and found that naturally occurring cyanophage genome sequence space is statistically clustered into discrete populations. These population-based, host-linked viral ecological data suggest that, for this single host and seawater sample alone, there are at least 26 double-stranded DNA viral populations with estimated relative abundances ranging from 0.06 to 18.2%. These populations include previously cultivated cyanophage and new viral types missed by decades of isolate-based studies. Nucleotide identities of homologous genes mostly varied by less than 1% within populations, even in hypervariable genome regions, and by 42-71% between populations, which provides benchmarks for viral metagenomics and genome-based viral species definitions. Together these findings showcase a new approach to viral ecology that quantitatively links objectively defined environmental viral populations, and their genomes, to their hosts. PMID:25043051

Deng, Li; Ignacio-Espinoza, J Cesar; Gregory, Ann C; Poulos, Bonnie T; Weitz, Joshua S; Hugenholtz, Philip; Sullivan, Matthew B

2014-09-11

357

Health Care-Acquired Viral Respiratory Diseases  

PubMed Central

Health care–associated viral respiratory infections, common among hospitalized children, also occur among adults and institutionalized persons and result in increased patient morbidity, mortality, and health care costs. Approximately 20% of patients with health care–associated pneumonia have viral respiratory infections, with 70% of these infections caused by adenovirus, influenza virus, parainfluenza virus, and respiratory syncytial virus (RSV).1 These infections typically reflect the level of viral activity within the community.1,2 This article focuses on the epidemiology, transmission, and control of health care–associated RSV and influenza virus. PMID:21316002

Goins, William P.; Talbot, H. Keipp; Talbot, Thomas R.

2014-01-01

358

A microfluidic system integrated with buried optical fibers for detection of Phalaenopsis orchid pathogens.  

PubMed

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

Lin, Chih-Lin; Chang, Wen-Hsin; Wang, Chih-Hung; Lee, Chia-Hwa; Chen, Tzong-Yueh; Jan, Fuh-Jyh; Lee, Gwo-Bin

2015-01-15

359

Analysis of viral microRNA expression by elephant endotheliotropic herpesvirus 1.  

PubMed

Elephant endotheliotropic herpesvirus 1 (EEHV1), a member of the Betaherpesvirinae subfamily, has recently emerged as an important viral pathogen of Asian elephants that can cause a severe, often fatal, hemorrhagic disease. EEHV1 does not replicate in culture and little is currently known about the molecular biology of this emerging pathogen, with the notable exception of its genomic DNA sequence. Here, we have used small RNA deep sequencing to determine whether EEHV1, like other human and murine betaherpesviruses, expresses viral microRNAs in infected tissues in vivo. Our data provide evidence supporting the existence of at least three novel viral microRNAs encoded by EEHV1 and one of these, miR-E3-5p, is shown to repress target mRNA expression. Moreover, miR-E3-5p expression was readily detectable in tissue samples derived from two infected elephants, including in whole blood. These data shed new light on the biology of EEHV1 and identify small RNAs that have the potential to be useful in the diagnosis of sub-clinical infections in captive Asian and African elephants. PMID:24725936

Furuse, Yuki; Dastjerdi, Akbar; Seilern-Moy, Katharina; Steinbach, Falko; Cullen, Bryan R

2014-04-01

360

Aptamer-Based Therapeutics: New Approaches to Combat Human Viral Diseases  

PubMed Central

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

Shum, Ka-To; Zhou, Jiehua; Rossi, John J.

2013-01-01

361

Viral hepatitis and hepatocellular carcinoma  

PubMed Central

Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The incidence of HCC varies considerably with the geographic area because of differences in the major causative factors. Chronic hepatitis B and C, mostly in the cirrhotic stage, are responsible for the great majority of cases of HCC worldwide. The geographic areas at the highest risk are South-East Asia and sub-Saharan Africa, here hepatitis B is highly endemic and is the main cause of HCC. In areas with an intermediate rate of HCC such as Southern Europe and Japan, hepatitis C is the predominant cause, whereas in low rate areas such as Northern Europe and the USA, HCC is often related to other factors as alcoholic liver disease. There is a rising incidence in HCC in developed countries during the last two decades, due to the increasing rate of hepatitis C infection and improvement of the clinical management of cirrhosis. Methods This article reviews the literature on hepatitis and hepatocellular carcinoma. The Medline search was carried out using these key words and articles were selected on epidemiology, risk factors, screening, and prevention of hepatocellular carcinoma. Results Screening of patients with advanced chronic hepatitis B and C with hepatic ultrasound and determination of serum alfa-fetoprotein may improve the detection of HCC, but further studies are needed whether screening improves clinical outcome. Hepatitis B and C viruses (HBV/HCV) can be implicated in the development of HCC in an indirect way, through induction of chronic inflammation, or directly by means of viral proteins or, in the case of HBV, by creation of mutations by integration into the genome of the hepatocyte. Conclusion The most effective tool to prevent HCC is avoidance of the risk factors such as viral infection. For HBV, a very effective vaccine is available. Preliminary data from Taiwan indicate a protective effect of universal vaccination on the development of HCC. Vaccination against HBV should therefore be a health priority. In patients with chronic hepatitis B or C, interferon-alfa treatment in a noncirrhotic stage is protective for HCC development in responders, probably by prevention of cirrhosis development. When cirrhosis is already present, the protective effect is less clear. For cirrhosis due to hepatitis B, a protective effect was demonstrated in Oriental, but not in European patients. For cirrhosis due to hepatitis C, interferon-alfa treatment showed to be protective in some studies, especially in Japan with a high incidence of HCC in untreated patients. Virological, but also merely biochemical response, seems to be associated with a lower risk of development of HCC. As most studies are not randomized controlled trials, no definitive conclusions on the long-term effects of interferon-alfa in HBV or HCV cirrhosis can be established. Especially in hepatitis C, prospective studies should be performed using the more potent reference treatments for cirrhotics, namely the combination of peginterferon and ribavirin. PMID:15907199

Michielsen, Peter P; Francque, Sven M; van Dongen, Jurgen L

2005-01-01

362

Viral kinetics and mathematical models.  

PubMed

Mathematical models can provide insights into the dynamics of viral diseases. Methods that were introduced to analyze human immunodeficiency virus dynamics in vivo can be modified to give insights into hepatitis C virus (HCV) dynamics, the mechanisms of action of interferon, and the consequences of giving different dosages of interferon. Patients received doses of 5, 10, or 15 mIU of interferon daily for 14 days followed by maintenance therapy of 5 mIU daily until day 90. HCV-RNA levels in serum dropped rapidly over the first 1 to 2 days of therapy. Comparing the kinetics of this response with mathematical models suggests that interferon acts by blocking the production or release of HCV virions from infected cells. The analysis further indicates that a daily dose of 5 mIU blocks approximately 80% of HCV production, and doses of 10 and 15 mIU block approximately 95% of HCV production. The serum level of HCV is approximately constant before treatment is initiated. Our model suggests that in order to maintain this constant level, on average, approximately 1 trillion virions are produced and cleared daily in an untreated HCV-infected person. The acute, rapid clearance of HCV, which occurs over the first 2 days of therapy, is followed by a slower phase of serum HCV decline. The rate of the second-phase decline may reflect the rate at which HCV-producing cells are killed, possibly by immune responses. Additional studies are needed to evaluate more fully the kinetics of the second-phase decline as well as its dose dependence and its predictive power with regard to eradication of HCV. PMID:10653457

Perelson, A S

1999-12-27

363

Aplastica Anemia And Viral Hepatitis  

PubMed Central

Acquired aplastic anemia (aAA) is a severe and rare disease, characterized by hematopoietic bone marrow failure and peripheral cytopenia. The pathophysiology is immune mediated in most cases, activated T1 lymphocytes have been identified as effector cells. The disease can be successfully treated with combined immunosuppressive therapy or allogeneic hematopoietic stem cell transplantation. Hepatitis-associated aplastic anemia (HAA) is a syndrome of bone marrow failure following the development of acute seronegative hepatitis. HAA syndrome most often affects young males who presented severe pancytopenia two to three months after an episode of acute hepatitis. The clinical course of hepatitis is more frequently benign but a fulminant severe course is also described. The bone marrow failure can be explosive and severe and it is usually fatal if untreated, no correlations have been observed between severity of hepatitis and AA. In none of the studies a specific virus could be identified and most cases are seronegative for known hepatitis viruses. The clinical characteristics and response to immunotherapy indicate a central role for immune-mediated mechanism in the pathogenesis of HAA. The initial target organ of the immune response is the liver as suggested by the time interval between hepatitis and the onset of bone marrow failure. Liver histology is characterized by T cell infiltrating the parenchyma as reported in acute hepatitis. Recently in HAA it has been demonstrated intrahepatic and blood lymphocytes with T cell repertoire similar to that of confirmed viral acute hepatitis. The expanded T cell clones return to a normal distribution after response to immunosuppressive treatment, suggesting the antigen or T cell clearance. Therapeutic options are the same as acquired aplastic anemia. PMID:21415960

Cudillo, Laura

2009-01-01

364

Viral envelope glycoproteins swing into action.  

PubMed

Analysis of tick-borne encephalitis virus E protein reveals considerable structural diversity in the glycoproteins that clothe enveloped viruses and hints at the conformational gyrations in this molecule that lead to viral fusion. PMID:8591041

Stuart, D; Gouet, P

1995-07-15

365

Viral and host control of cytomegalovirus maturation  

PubMed Central

Maturation in herpesviruses initiates in the nucleus of the infected cell with encapsidation of viral DNA to form nucleocapsids and concludes with envelopment in the cytoplasm to form infectious virions that egress the cell. The entire process of virus maturation is orchestrated by protein-protein interactions and enzymatic activities of viral and host origin. Viral tegument proteins play important roles in maintaining the structural stability of capsids and directing the acquisition of virus envelope. Envelopment occurs at modified host membranes and exploits host vesicular trafficking. In this review, we summarize the current knowledge and concepts in human cytomegalovirus (HCMV) maturation and their parallels in other herpesviruses with an emphasis on viral and host factors regulating this process. PMID:22633075

Tandon, Ritesh; Mocarski, Edward S.

2012-01-01

366

In vivo analyses of viral RNA translation.  

PubMed

Positive-strand RNA viruses often use noncanonical strategies to usurp the host translational machinery for their own benefit. These strategies have been analyzed using transient expression assays in the absence of replication, with reporter genes replacing viral genes. A sensitive and convenient reporter assay is the dual luciferase system using Renilla (Renilla reniformis) and firefly (Photinus pyralis) reporter genes. Use of recombinant viral constructs containing the reporter luciferase gene allows us to discern whether a particular RNA sequence or secondary structure elicits an effect on initiation of translation or recoding. This chapter describes a standard luciferase protocol that can be molded to fit any viral sequence, in order to detect cis-acting regulatory elements in viral RNA. PMID:18370250

Staplin, William R; Miller, W Allen

2008-01-01

367

[Viral safety of biological medicinal products].  

PubMed

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

Stühler, A; Blümel, J

2014-10-01

368

VIROLOGY: Sensing Viral RNA Amid Your Own  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required: Viral RNA has a structural modification that cells recognize. This modification could be used in antiviral therapies and to modulate the immune system.

Takashi Fujita (Kyoto University;Institute for Virus Research,)

2006-11-10

369

Fungal pathogens of Proteaceae.  

PubMed

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

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

370

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

PubMed

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 0.67g of dried pancreatin resuspended in 13.5mL of cell culture medium followed by a 50-fold dilution in cell culture medium before spiking. After heating at 60±1°C for 5h, 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

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

2014-11-01

371

MODELING HOST-PATHOGEN INTERACTIONS: COMPUTATIONAL BIOLOGY AND BIOINFORMATICS FOR INFECTIOUS DISEASE RESEARCH (Session introduction)  

SciTech Connect

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.

McDermott, Jason E.; Braun, Pascal; Bonneau, Richard A.; Hyduke, Daniel R.

2011-12-01

372

Comparison of fecal indicators with pathogenic bacteria and rotavirus in groundwater  

PubMed Central

Groundwater is routinely analyzed for fecal indicators but direct comparisons of fecal indicators to the presence of bacterial and viral pathogens are rare. This study was conducted in rural Bangladesh where the human population density is high, sanitation is poor, and groundwater pumped from shallow tubewells is often contaminated with fecal bacteria. Five indicator microorganisms (E. coli, total coliform, F+RNA coliphage, Bacteroides and human-associated Bacteroides) and various environmental parameters were compared to the direct detection of waterborne pathogens by quantitative PCR in groundwater pumped from 50 tubewells. Rotavirus was detected in groundwater filtrate from the largest proportion of tubewells (40%), followed by Shigella (10%), Vibrio (10%), and pathogenic E. coli (8%). Spearman rank correlations and sensitivity-specificity calculations indicate that some, but not all, combinations of indicators and environmental parameters can predict the presence of pathogens. Culture-dependent fecal indicator bacteria measured on a single date did not predict total bacterial pathogens, but annually averaged monthly measurements of culturable E. coli did improve prediction for total bacterial pathogens. A qPCR-based E. coli assay was the best indicator for the bacterial pathogens. F+RNA coliphage were neither correlated nor sufficiently sensitive towards rotavirus, but were predictive of bacterial pathogens. Since groundwater cannot be excluded as a significant source of diarrheal disease in Bangladesh and neighboring countries with similar characteristics, the need to develop more effective methods for screening tubewells with respect to microbial contamination is necessary. PMID:22705866

Ferguson, Andrew S.; Layton, Alice C.; Mailloux, Brian J; Culligan, Patricia J.; Williams, Daniel E.; Smartt, Abby E.; Sayler, Gary S.; Feighery, John; McKay, Larry; Knappett, Peter S.K.; Alexandrova, Ekaterina; Arbit, Talia; Emch, Michael; Escamilla, Veronica; Ahmed, Kazi Matin; Alam, Md. Jahangir; Streatfield, P. Kim; Yunus, Mohammad; van Geen, Alexander

2012-01-01

373

Ribosomal Frameshifting in Decoding Plant Viral RNAs  

Microsoft Academic Search

\\u000a Frameshifting provides an elegant mechanism by which viral RNA both encodes overlapping genes and controls expression levels\\u000a of those genes. As in animal viruses, the ?1 ribosomal frameshift site in the viral mRNA consists of a canonical shifty heptanucleotide\\u000a followed by a highly structured frameshift stimulatory element, and the gene translated as a result of frameshifting usually\\u000a encodes the RNA-dependent

W. Allen Miller; David P. Giedroc

374

Neutrophil in Viral Infections, Friend or Foe?  

PubMed Central

Polymorphonuclear leukocytes or neutrophils are the first immune cells to the site of injury and microbial infection. Neutrophils are crucial players in controlling bacterial and fungal infections, and in particular secondary infections, by phagocytosis, degranulation and neutrophil extracellular traps (NETs). While neutrophils have been shown to play important roles in viral pathogenesis, there is a lack of detailed investigation. In this article, we will review recent progresses toward understanding the role of neutrophils in viral pathogenesis. PMID:23178588

Drescher, Brandon; Bai, Fengwei

2012-01-01

375

Innate immune recognition of viral infection  

Microsoft Academic Search

Induction of the antiviral innate immune response depends on recognition of viral components by host pattern-recognition receptors. Members of the Toll-like receptor family have emerged as key sensors that recognize viral components such as nucleic acids. Toll-like receptor signaling results in the production of type I interferon and inflammatory cytokines and leads to dendritic cell maturation and establishment of antiviral

Taro Kawai; Shizuo Akira

2006-01-01

376

The contribution of viral genotype to plasma viral set-point in HIV infection.  

PubMed

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

Hodcroft, Emma; Hadfield, Jarrod D; Fearnhill, Esther; Phillips, Andrew; Dunn, David; O'Shea, Siobhan; Pillay, Deenan; Leigh Brown, Andrew J

2014-05-01

377

A Conserved Gammaherpesvirus Protein Kinase Targets Histone Deacetylases 1 and 2 To Facilitate Viral Replication in Primary Macrophages  

PubMed Central

Gammaherpesviruses are ubiquitious pathogens that establish lifelong infection and are associated with several malignancies. All gammaherpesviruses encode a conserved protein kinase that facilitates viral replication and chronic infection and thus represents an attractive therapeutic target. In this study, we identify a novel function of gammaherpesvirus protein kinase as a regulator of class I histone deacetylases (HDAC). Mouse gammaherpesvirus 68 (MHV68)-encoded protein kinase orf36 interacted with HDAC1 and 2 and prevented association of these HDACs with the viral promoter driving expression of RTA, a critical immediate early transcriptional activator. Furthermore, the ability to interact with HDAC1 and 2 was not limited to the MHV68 orf36, as BGLF4, a related viral protein kinase encoded by Epstein-Barr virus, interacted with HDAC1 in vitro. Importantly, targeting of HDAC1 and 2 by orf36 was independent of the kinase's enzymatic activity. Additionally, orf36 expression, but not its enzymatic activity, induced changes in the global deacetylase activity observed in infected primary macrophages. Combined deficiency of HDAC1 and 2 rescued attenuated replication and viral DNA synthesis of the orf36 null MHV68 mutant, indicating that the regulation of HDAC1 and 2 by orf36 was relevant for viral replication. Understanding the mechanism by which orf36 facilitates viral replication, including through HDAC targeting, will facilitate the development of improved therapeutics against gammaherpesvirus kinases. PMID:23616648

Mounce, Bryan C.; Mboko, Wadzanai P.; Bigley, Tarin M.; Terhune, Scott S.

2013-01-01

378

Novel restriction factor RNA-associated early-stage anti-viral factor (REAF) inhibits human and simian immunodeficiency viruses  

PubMed Central

Background The discovery of novel anti-viral restriction factors illuminates unknown aspects of innate sensing and immunity. We identified RNA-associated Early-stage Anti-viral Factor (REAF) using a whole genome siRNA screen for restriction factors to human immunodeficiency virus (HIV) that act in the early phase of viral replication. Results We observed more than 50 fold rescue of HIV-1 infection, using a focus forming unit (FFU) assay, following knockdown of REAF by specific siRNA. Quantitative PCR was used to show that REAF knockdown results in an increase of early and late reverse transcripts which impacts the level of integration. REAF thus appears to act at an early stage of the viral life cycle during reverse transcription. Conversely when REAF is over-expressed in target cells less infected cells are detectable and fewer reverse transcripts are produced. Human REAF can also inhibit HIV-2 and simian immunodeficiency virus (SIV) infection. REAF associates with viral nucleic acids and may act to prevent reverse transcription. Conclusions This report firmly places REAF alongside APOBECs and SAMHD1 as a potent inhibitor of HIV replication acting early in the replication cycle, just after cell entry. We propose that REAF is part of an anti-viral surveillance system destroying incoming retroviruses. This novel mechanism could apply to invasion of cells by any intracellular pathogen. PMID:24410916

2014-01-01

379

Host MicroRNA Regulation of Human Cytomegalovirus Immediate Early Protein Translation Promotes Viral Latency  

PubMed Central

ABSTRACT Reactivation of human cytomegalovirus (HCMV) is a significant cause of disease and death in immunocompromised patients, underscoring the need to understand how latency is controlled. Here we demonstrate that HCMV has evolved to utilize cellular microRNAs (miRNAs) in cells that promote latency to regulate expression of a viral protein critical for viral reactivation. Our data reveal that hsa-miR-200 miRNA family members target the UL122 (immediate early protein 2) 3? untranslated region, resulting in repression of this viral protein. Utilizing recombinant viruses that mutate the miRNA-binding site compared to the sequence of the wild-type virus results in lytic rather than latent infections in ex vivo infections of primary CD34+ cells. Cells permissive for lytic replication demonstrate low levels of these miRNAs. We propose that cellular miRNA regulation of HCMV is critical for maintenance of viral latency. IMPORTANCE Human cytomegalovirus (HCMV) is a herpesvirus that infects a majority of the population. Once acquired, individuals harbor the virus for life, where the virus remains, for the most part, in a quiet or latent state. Under weakened immune conditions, the virus can reactivate, which can cause severe disease and often death. We have found that members of a family of small RNAs, termed microRNAs, encoded by human myeloid progenitor cells are capable of repressing a key viral protein, thus enabling the virus to ensure a quiet/latent state. As these progenitor cells mature further down the myeloid lineage toward cells that support active viral replication, the levels of these microRNAs decrease. Together, our data suggest that host cell microRNA regulation of HCMV is important for the quiet/latent state of this pathogen. PMID:24599990

O'Connor, Christine M.

2014-01-01

380

Generating viral metagenomes from the coral holobiont.  

PubMed

Reef-building corals comprise multipartite symbioses where the cnidarian animal is host to an array of eukaryotic and prokaryotic organisms, and the viruses that infect them. These viruses are critical elements of the coral holobiont, serving not only as agents of mortality, but also as potential vectors for lateral gene flow, and as elements encoding a variety of auxiliary metabolic functions. Consequently, understanding the functioning and health of the coral holobiont requires detailed knowledge of the associated viral assemblage and its function. Currently, the most tractable way of uncovering viral diversity and function is through metagenomic approaches, which is inherently difficult in corals because of the complex holobiont community, an extracellular mucus layer that all corals secrete, and the variety of sizes and structures of nucleic acids found in viruses. Here we present the first protocol for isolating, purifying and amplifying viral nucleic acids from corals based on mechanical disruption of cells. This method produces at least 50% higher yields of viral nucleic acids, has very low levels of cellular sequence contamination and captures wider viral diversity than previously used chemical-based extraction methods. We demonstrate that our mechanical-based method profiles a greater diversity of DNA and RNA genomes, including virus groups such as Retro-transcribing and ssRNA viruses, which are absent from metagenomes generated via chemical-based methods. In addition, we briefly present (and make publically available) the first paired DNA and RNA viral metagenomes from the coral Acropora tenuis. PMID:24847321

Weynberg, Karen D; Wood-Charlson, Elisha M; Suttle, Curtis A; van Oppen, Madeleine J H

2014-01-01

381

Viral Metagenomics: MetaView Software  

SciTech Connect

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.

Zhou, C; Smith, J

2007-10-22

382

Emergence of a Highly Pathogenic Avian Influenza Virus from a Low-Pathogenic Progenitor  

PubMed Central

ABSTRACT Avian influenza (AI) viruses of the H7 subtype have the potential to evolve into highly pathogenic (HP) viruses that represent a major economic problem for the poultry industry and a threat to global health. However, the emergence of HPAI viruses from low-pathogenic (LPAI) progenitor viruses currently is poorly understood. To investigate the origin and evolution of one of the most important avian influenza epidemics described in Europe, we investigated the evolutionary and spatial dynamics of the entire genome of 109 H7N1 (46 LPAI and 63 HPAI) viruses collected during Italian H7N1 outbreaks between March 1999 and February 2001. Phylogenetic analysis revealed that the LPAI and HPAI epidemics shared a single ancestor, that the HPAI strains evolved from the LPAI viruses in the absence of reassortment, and that there was a parallel emergence of mutations among HPAI and later LPAI lineages. Notably, an ultradeep-sequencing analysis demonstrated that some of the amino acid changes characterizing the HPAI virus cluster were already present with low frequency within several individual viral populations from the beginning of the LPAI H7N1 epidemic. A Bayesian phylogeographic analysis revealed stronger spatial structure during the LPAI outbreak, reflecting the more rapid spread of the virus following the emergence of HPAI. The data generated in this study provide the most complete evolutionary and phylogeographic analysis of epidemiologically intertwined high- and low-pathogenicity viruses undertaken to date and highlight the importance of implementing prompt eradication measures against LPAI to prevent the appearance of viruses with fitness advantages and unpredictable pathogenic properties. IMPORTANCE The Italian H7 AI epidemic of 1999 to 2001 was one of the most important AI outbreaks described in Europe. H7 viruses have the ability to evolve into HP forms from LP precursors, although the mechanisms underlying this evolutionary transition are only poorly understood. We combined epidemiological information, whole-genome sequence data, and ultradeep sequencing approaches to provide the most complete characterization of the evolution of HPAI from LPAI viruses undertaken to date. Our analysis revealed that the LPAI viruses were the direct ancestors of the HPAI strains and identified low-frequency minority variants with HPAI mutations that were present in the LPAI samples. Spatial analysis provided key information for the design of effective control strategies for AI at both local and global scales. Overall, this work highlights the importance of implementing rapid eradication measures to prevent the emergence of novel influenza viruses with severe pathogenic properties. PMID:24501401

Fusaro, Alice; Nelson, Martha I.; Bonfanti, Lebana; Mulatti, Paolo; Hughes, Joseph; Murcia, Pablo R.; Schivo, Alessia; Valastro, Viviana; Moreno, Ana; Holmes, Edward C.; Cattoli, Giovanni

2014-01-01

383

Molecular Design, Functional Characterization and Structural Basis of a Protein Inhibitor Against the HIV1 Pathogenicity Factor Nef  

Microsoft Academic Search

Increased spread of HIV-1 and rapid emergence of drug resistance warrants development of novel antiviral strategies. Nef, a critical viral pathogenicity factor that interacts with host cell factors but lacks enzymatic activity, is not targeted by current antiviral measures. Here we inhibit Nef function by simultaneously blocking several highly conserved protein interaction surfaces. This strategy, referred to as “wrapping Nef”,

Sebastian Breuer; Simone I. Schievink; Antje Schulte; Wulf Blankenfeldt; Oliver T. Fackler; Matthias Geyer

2011-01-01

384

Host behavior alters spiny lobster-viral disease dynamics: a simulation study.  

PubMed

Social behavior confers numerous benefits to animals but also risks, among them an increase in the spread of pathogenic diseases. We examined the trade-off between risk of predation and disease transmission under different scenarios of host spatial structure and disease avoidance behavior using a spatially explicit, individual-based model of the host pathogen interaction between juvenile Caribbean spiny lobster (Panulirus argus) and Panulirus argus Virus 1 (PaV1). Spiny lobsters are normally social but modify their behavior to avoid diseased conspecifics, a potentially effective means of reducing transmission but one rarely observed in the wild. We found that without lobster avoidance of diseased conspecifics, viral outbreaks grew in intensity and duration in simulations until the virus was maintained continuously at unrealistically high levels. However, when we invoked disease avoidance at empirically observed levels, the intensity and duration of outbreaks was reduced and the disease extirpated within five years. Increased lobster (host) spatial aggregation mimicking that which occurs when sponge shelters for lobsters are diminished by harmful algal blooms, did not significantly increase PaV1 transmission or persistence in lobster populations. On the contrary, behavioral aversion of diseased conspecifics effectively reduced viral prevalence, even when shelters were limited, which reduced shelter availability for all lobsters but increased predation, especially of infected lobsters. Therefore, avoidance of diseased conspecifics selects against transmission by contact, promotes alternative modes of transmission, and results in a more resilient host-pathogen system. PMID:25230484

Dolan, Thomas W; Butler, Mark J; Shields, Jeffrey D

2014-08-01

385

Effects of Factors Related to Water Quality and Population Density on the Sensitivity of Juvenile Largemouth Bass to Mortality Induced by Viral Infection  

Microsoft Academic Search

Environmental stressors can predispose fish to mortality from infectious disease. This study examined the effects of two factors, water quality and physical crowding, on the responses of fish to viral infection. Juvenile largemouth bass Micropterus salmoides were experimentally inoculated with largemouth bass virus (LMBV), an emerging pathogen in the family Iridoviridae. In separate experiments, fish were exposed to various concentrations

Kate R. Inendino; Emily C. Grant; David P. Philipp; Tony L. Goldberg

2005-01-01

386

Similarities and dissimilarities in the structure and expression of viral genomes of various virus strains immunologically related to Marek's disease virus  

Microsoft Academic Search

Summary Various strains immunologically related to Marek's disease virus (MDV) have been subdivided into three serotypes: serotype 1, pathogenic strains of MDV and attenuated or apathogenic variants derived from them; serotype 2, naturally occuring apathogenic strains of MDV; serotype 3, herpesvirus of turkey (HVT). The viral genome structures of these three serotypes were compared by a simple, practical method using

K. Hirai; K. Nakajima; K. Ikuta; R. Kirisawa; Y. Kawakami; T. Mikami; S. Kato

1986-01-01

387

Role for Bovine Viral Diarrhea Virus Erns Glycoprotein in the Control of Activation of Beta Interferon by Double-Stranded RNA  

Microsoft Academic Search

Bovine viral diarrhea virus (BVDV) is a Pestivirus belonging to the family Flaviviridae and is a major pathogen of cattle throughout the world with an incidence of infection often in excess of 70% (9, 24). An unusual feature of pestiviruses is their ability to sustain a persistent infection after in utero infection of a fetus. BVDV exists as two biotypes

Munir Iqbal; Emma Poole; Stephen Goodbourn; John W. McCauley

2004-01-01

388

Type I Interferon Reaction to Viral Infection in Interferon-Competent, Immortalized Cell Lines from the African Fruit Bat Eidolon helvum  

Microsoft Academic Search

Bats harbor several highly pathogenic zoonotic viruses including Rabies, Marburg, and henipaviruses, without overt clinical symptoms in the animals. It has been suspected that bats might have evolved particularly effective mechanisms to suppress viral replication. Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E.

Susanne E. Biesold; Daniel Ritz; Florian Gloza-Rausch; Robert Wollny; Jan Felix Drexler; Victor M. Corman; Elisabeth K. V. Kalko; Samuel Oppong; Christian Drosten; Marcel A. Müller

2011-01-01

389

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

Microsoft Academic Search

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

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

2010-01-01

390

Common themes in microbial pathogenicity.  

PubMed Central

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

Finlay, B B; Falkow, S

1989-01-01

391

Proteomics of Foodborne Bacterial Pathogens  

NASA Astrophysics Data System (ADS)

This chapter is intended to be a relatively brief overview of proteomic techniques currently in use for the identification and analysis of microorganisms with a special emphasis on foodborne pathogens. The chapter is organized as follows. First, proteomic techniques are introduced and discussed. Second, proteomic applications are presented specifically as they relate to the identification and qualitative/quantitative analysis of foodborne pathogens.

Fagerquist, Clifton K.

392

Cytopathic bovine viral diarrhea viruses (BVDV): emerging pestiviruses doomed to extinction  

PubMed Central

Bovine viral diarrhea virus (BVDV), a Flaviviridae pestivirus, is arguably one of the most widespread cattle pathogens worldwide. Each of its two genotypes has two biotypes, non-cytopathic (ncp) and cytopathic (cp). Only the ncp biotype of BVDV may establish persistent infection in the fetus when infecting a dam early in gestation, a time point which predates maturity of the adaptive immune system. Such fetuses may develop and be born healthy but remain infected for life. Due to this early initiation of fetal infection and to the expression of interferon antagonistic proteins, persistently infected (PI) animals remain immunotolerant to the infecting viral strain. Although only accounting for some 1% of all animals in regions where BVDV is endemic, PI animals ensure the viral persistence in the host population. These animals may, however, develop the fatal mucosal disease, which is characterized by widespread lesions in the gastrointestinal tract. Cp BVD virus, in addition to the persisting ncp biotype, can be isolated from such animals. The cp viruses are characterized by unrestrained genome replication, and their emergence from the persisting ncp ones is due to mutations that are unique in each virus analyzed. They include recombinations with host cell mRNA, gene translocations and duplications, and point mutations. Cytopathic BVD viruses fail to establish chains of infection and are unable to cause persistent infection. Hence, these viruses illustrate a case of “viral emergence to extinction” – irrelevant for BVDV evolution, but fatal for the PI host. PMID:20197026

Peterhans, Ernst; Bachofen, Claudia; Stalder, Hanspeter; Schweizer, Matthias

2010-01-01

393

Point-of-Care Microdevices for Blood Plasma Analysis in Viral Infectious Diseases.  

PubMed

Each year, outbreaks of viral infections cause illness, disability, death, and economic loss. As learned from past incidents, the detrimental impact grows exponentially without effective quarantine. Therefore, rapid on-site detection and analysis are highly desired. In addition, for high-risk areas of viral contamination, close monitoring should be provided during the potential disease incubation period. As the epidemic progresses, a response protocol needs tobe rapidly implemented and the virus evolution fully tracked. For these scenarios, point-of-care microdevices can provide sensitive, accurate, rapid and low-cost analysis for a large population, especially in handling complex patient samples, such as blood, urine and saliva. Blood plasma can be considered as a mine of information containing sources and clues of biomarkers, including nucleic acids, immunoglobulin and other proteins, as well as pathogens for clinical diagnosis. However, blood plasma is also the most complicated body fluid. For targeted plasma biomarker detection or untargeted plasma biomarker discovery, the challenges can be as difficult as identifying a needle in a haystack. A useful platform must not only pursue single performance characteristics, but also excel at multiple performance parameters, such as speed, accuracy, sensitivity, selectivity, cost, portability, reliability, and user friendliness. Throughout the decades, tremendous progress has been made in point-of-care microdevices for viral infectious diseases. In this paper, we review fully integrated lab-on-chip systems for blood analysis of viral infectious disease. PMID:24879614

Yeh, Yin-Ting; Nisic, Merisa; Yu, Xu; Xia, Yiqiu; Zheng, Si-Yang

2014-11-01

394

The Viral Replication Complex Is Associated with the Virulence of Newcastle Disease Virus?  

PubMed Central

Virulent strains of Newcastle disease virus ([NDV] also known as avian paramyxovirus type 1) can be discriminated from low-virulence strains by the presence of multiple basic amino acid residues at the proteolytic cleavage site of the fusion (F) protein. However, some NDV variants isolated from pigeons (pigeon paramyxovirus type 1 [PPMV-1]) have low levels of virulence, despite the fact that their F protein cleavage sites contain a multibasic amino acid sequence and have the same functionality as that of virulent strains. To determine the molecular basis of this discrepancy, we examined the role of the internal proteins in NDV virulence. Using reverse genetics, the genes encoding the nucleoprotein (NP), phosphoprotein (P), matrix protein (M), and large polymerase protein (L) were exchanged between the nonvirulent PPMV-1 strain AV324 and the highly virulent NDV strain Herts. Recombinant viruses were evaluated for their pathogenicities and replication levels in day-old chickens, and viral genome replication and plaque sizes were examined in cell culture monolayers. We also tested the contributions of the individual NP, P, and L proteins to the activity of the viral replication complex in an in vitro replication assay. The results showed that the replication proteins of Herts are more active than those of AV324 and that the activity of the viral replication complex is directly related to virulence. Although the M protein affected viral replication in vitro, it had only a minor effect on virulence. PMID:20660202

Dortmans, J. C. F. M.; Rottier, P. J. M.; Koch, G.; Peeters, B. P. H.

2010-01-01

395

Averaging of Viral Envelope Glycoprotein Spikes from Electron Cryotomography Reconstructions using Jsubtomo.  

PubMed

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

Huiskonen, Juha T; Parsy, Marie-Laure; Li, Sai; Bitto, David; Renner, Max; Bowden, Thomas A

2014-01-01

396

QuRe: software for viral quasispecies reconstruction from next-generation sequencing data  

PubMed Central

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

Prosperi, Mattia C. F.; Salemi, Marco

2012-01-01

397

Subversion of the actin cytoskeleton during viral infection  

Microsoft Academic Search

Viral infection converts the normal functions of a cell to optimize viral replication and virion production. One striking observation of this conversion is the reconfiguration and reorganization of cellular actin, affecting every stage of the viral life cycle, from entry through assembly to egress. The extent and degree of cytoskeletal reorganization varies among different viral infections, suggesting the evolution of

Matthew P. Taylor; Orkide O. Koyuncu; Lynn W. Enquist

2011-01-01

398

Characterization of Marburg virus glycoprotein in viral entry  

Microsoft Academic Search

One major determinant of host tropism for filoviruses is viral glycoprotein (GP), which is involved in receptor binding and viral entry. Compared to Ebola GP (EGP), Marburg GP (MGP) is less well characterized in viral entry. In this study, using a human immunodeficiency virus-based pseudotyped virus as a surrogate system, we have characterized the role of MGP in viral entry.

Balaji Manicassamy; Jizhen Wang; Emily Rumschlag; Stéphanie Tymen; Valentina Volchkova; Viktor Volchkov; Lijun Rong

2007-01-01

399

Development of Multiplex PCRs for Detection of Common Viral Pathogens and Agents of Congenital Infections  

Microsoft Academic Search

Potential causes of congenital infection include Toxoplasma gondii and viruses such as cytomegalovirus (CMV), enterovirus, hepatitis C virus, herpes simplex virus types 1 and 2 (HSV-1 and -2), human herpesvirus types 6, 7, and 8, lymphocytic choriomeningitis virus, parvovirus, rubella virus, and varicella-zoster virus. Testing for each of these agents using nucleic acid tests is time consuming and the availability

C. J. McIver; C. F. H. Jacques; S. S. W. Chow; S. C. Munro; G. M. Scott; J. A. Roberts; M. E. Craig; W. D. Rawlinson

2005-01-01

400

Synthetic Protocells Interact with Viral Nanomachinery and Inactivate Pathogenic Human Virus  

PubMed Central

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

Moscona, Anne; LaVan, David A.

2011-01-01

401

Antibodies to selected viral and bacterial pathogens in European wild boars from southcentral Spain.  

PubMed

Serum samples from 78 European wild boars (Sus scrofa) harvested during the 1999-2000 hunting season were tested for antibodies to Brucella spp., classical swine fever virus, Erysipelothrix rhusiopathiae, Haemophilus parasuis, Leptospira interrogans serovar pomona, Mycoplasma hyopneumoniae, pseudorabies virus (PRV), porcine parvovirus (PPV), porcine reproductive and respiratory syndrome virus, Salmonella serogroups B, C, and D, Streptococcus suis, and swine influenza virus (SIV) serotypes H1N1 and H3N2. Samples were collected from Sierra Morena and Montes de Toledo in southcentral Spain. Antibodies were detected to PRV (36%), L. interrogans serovar pomona (12%), PPV (10%), E. rhusiopathiae (5%), SIV serotype H1N1 (4%), Salmonella serogroup B (4%), and Salmonella serogroup C (3%). Our results suggest that more research is needed to describe the epidemiology of infectious diseases of Spanish wild boars. PMID:12238391

Vicente, Joaquín; León-Vizcaíno, Luís; Gortázar, Christian; José Cubero, María; González, Mónica; Martín-Atance, Pablo

2002-07-01

402

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

Microsoft Academic Search

ABSTRACT: 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

Joaqu? N Vicente; Lu? S Leo N-vizca? No; Christian Gorta Zar; Mar? A Jose Cubero; Mo Nica Gonza Lez

403

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

Microsoft Academic Search

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,

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

404

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

E-print Network

of Fabricius be- fore the precursor cells have migrated from the bursa drastically reduced stem cell migration and subsequent production of humoral antibody (2, 20, 21). No work has so far been reported on the effects of irradiat1on, cyclophosphamide... of Fabricius be- fore the precursor cells have migrated from the bursa drastically reduced stem cell migration and subsequent production of humoral antibody (2, 20, 21). No work has so far been reported on the effects of irradiat1on, cyclophosphamide...

Pugh, Roberta Ann

2012-06-07

405

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

PubMed

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

Kingscote, B F; Bohac, J G

1986-10-01

406

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

Microsoft Academic Search

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)

B. F. Kingscote; J. G. Bohac

407

Viral Pathogens and Severe Acute Respiratory Syndrome: Oligodynamic Ag1 for Direct Immune Intervention  

Microsoft Academic Search

This retrospective study of silver-based therapeutics briefly reviews their history, and then explores the modern application of charged silver particles, especially as an antiviral agent. The recent outbreak of severe acute respiratory syndrome (SARS) suggests this is timely. Medical literature shows that a variety of viruses have been successfully treated with silver- based drugs. However, 'silver salts' and\\/or inferior silver

ERIC J. RENTZ

408

Diseases and pathogens associated with mortality in Ontario beef feedlots.  

PubMed

This study determined the prevalence of diseases and pathogens associated with mortality or severe morbidity in 72 Ontario beef feedlots in calves that died or were euthanized within 60 days after arrival. Routine pathologic and microbiologic investigations, as well as immunohistochemical staining for detection of bovine viral diarrhea virus (BVDV) antigen, were performed on 99 calves that died or were euthanized within 60 days after arrival. Major disease conditions identified included fibrinosuppurative bronchopneumonia (49%), caseonecrotic bronchopneumonia or arthritis (or both) caused by Mycoplasma bovis (36%), viral respiratory disease (19%), BVDV-related diseases (21%), Histophilus somni myocarditis (8%), ruminal bloat (2%), and miscellaneous diseases (8%). Viral infections identified were BVDV (35%), bovine respiratory syncytial virus (9%), bovine herpesvirus-1 (6%), parainfluenza-3 virus (3%), and bovine coronavirus (2%). Bacteria isolated from the lungs included M. bovis (82%), Mycoplasma arginini (72%), Ureaplasma diversum (25%), Mannheimia haemolytica (27%), Pasteurella multocida (19%), H. somni (14%), and Arcanobacterium pyogenes (19%). Pneumonia was the most frequent cause of mortality of beef calves during the first 2 months after arrival in feedlots, representing 69% of total deaths. The prevalence of caseonecrotic bronchopneumonia caused by M. bovis was similar to that of fibrinosuppurative bronchopneumonia, and together, these diseases were the most common causes of pneumonia and death. M. bovis pneumonia and polyarthritis has emerged as an important cause of mortality in Ontario beef feedlots. PMID:16566254

Gagea, Mihai I; Bateman, Kenneth G; van Dreumel, Tony; McEwen, Beverly J; Carman, Susy; Archambault, Marie; Shanahan, Rachel A; Caswell, Jeff L

2006-01-01

409

Viral Replication and Lung Lesions in BALB/c Mice Experimentally Inoculated with Avian Metapneumovirus Subgroup C Isolated from Chickens  

PubMed Central

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 inocu