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molecular determinants of mouse neurovirulence and mosquito infection for western equine encephalitis virus.western equine encephalitis virus (weev) is a naturally occurring recombinant virus derived from ancestral sindbis and eastern equine encephalitis viruses. we previously showed that infection by weev isolates mcmillan (mcm) and imp-181 (imp) results in high (∼90-100%) and low (0%) mortality, respectively, in outbred cd-1 mice when virus is delivered by either subcutaneous or aerosol routes. however, relatively little is known about specific virulence determinants of weev. we previously observed ...201323544138
productive homologous and non-homologous recombination of hepatitis c virus in cell culture.genetic recombination is an important mechanism for increasing diversity of rna viruses, and constitutes a viral escape mechanism to host immune responses and to treatment with antiviral compounds. although rare, epidemiologically important hepatitis c virus (hcv) recombinants have been reported. in addition, recombination is an important regulatory mechanism of cytopathogenicity for the related pestiviruses. here we describe recombination of hcv rna in cell culture leading to production of infe ...201323555245
validation of a cell-based elisa as a screening tool identifying anti-alphavirus small-molecule inhibitors.venezuelan (veev), eastern, and western equine encephalitis viruses, members of the genus alphavirus, are causative agents of debilitative and sometimes fatal encephalitis. although human cases are rare, these viruses pose a threat to military personnel, and to public health, due to their potential use as bioweapons. currently, there are no licensed therapeutics for treating alphavirus infections. to address this need, small-molecules with potential anti-alphavirus activity, provided by collabor ...201323764417
the role of e3 in ph protection during alphavirus assembly and exit.alphaviruses are small enveloped viruses whose surface is covered by spikes composed of trimers of e2/e1 glycoprotein heterodimers. during virus entry, the e2/e1 dimer dissociates within the acidic endosomal environment, freeing the e1 protein to mediate fusion of the viral and endosome membranes. e2 is synthesized as a precursor, p62, which is cleaved by furin in the late secretory pathway to produce mature e2 and a small peripheral glycoprotein, e3. the immature p62/e1 dimer is acid resistant, ...201323864626
effects of nasal or pulmonary delivered treatments with an adenovirus vectored interferon (mdef201) on respiratory and systemic infections in mice caused by cowpox and vaccinia viruses.an adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mdef201) was evaluated for efficacy against lethal cowpox (brighton strain) and vaccinia (wr strain) virus respiratory and systemic infections in mice. two routes of mdef201 administration were used, nasal sinus (5-µl) and pulmonary (50-µl), to compare differences in efficacy, since the preferred treatment of humans would be in a relatively small volume delivered intranasally. lower respiratory infections (lri), upper respira ...201323874722
identification of hotspots in the european union for the introduction of four zoonotic arboviroses by live animal trade.live animal trade is considered a major mode of introduction of viruses from enzootic foci into disease-free areas. due to societal and behavioural changes, some wild animal species may nowadays be considered as pet species. the species diversity of animals involved in international trade is thus increasing. this could benefit pathogens that have a broad host range such as arboviruses. the objective of this study was to analyze the risk posed by live animal imports for the introduction, in the e ...201323894573
prolonged polyarthralgia in a german traveller with mayaro virus infection without inflammatory correlates.mayaro virus is endemic in south america and sporadic outbreaks have been described. it causes a dengue-like febrile illness accompanied by severe and long-lasting polyarthralgias. outside endemic regions, however, the disease is not well known and can be misdiagnosed as dengue. international travellers are at risk to acquire mayaro virus and due to increased worldwide travel infectious disease specialists need to be aware of such rare clinical entities.201323927600
use of staged molecular analysis to determine causes of unexplained central nervous system infections.no agent is implicated in most central nervous system (cns) infections. to investigate cerebrospinal fluid samples from patients with cns infections of unknown cause in 1 hospital in taiwan, we used a staged molecular approach, incorporating techniques including multiplex masstag pcr, 16s rrna pcr, dna microarray, and high-throughput pyrosequencing. we determined the infectious agent for 31 (24%) of 131 previously negative samples. candidate pathogens were identified for 25 (27%) of 94 unexplain ...201323965845
powassan meningoencephalitis, new york, new york, usa.disease caused by powassan virus (powv), a tick-borne flavivirus, ranges from asymptomatic to severe neurologic compromise and death. two cases of powv meningoencephalitis in new york, usa, highlight diagnostic techniques, neurologic outcomes, and the effect of powv on communities to which it is endemic.023969017
decontamination of high-risk animal and zoonotic pathogens.preparedness for the decontamination of affected environments, premises, facilities, and products is one prerequisite for an immediate response to an animal disease outbreak. various information sources provide recommendations on how to proceed in an outbreak situation to eliminate biological contaminants and to stop the spread of the disease. in order to facilitate the identification of the right decontamination strategy, we present an overview of relevant references for a collection of pathoge ...201323971795
how much can diptera-borne viruses persist over unfavourable seasons?diptera are vectors of major human and animal pathogens worldwide, such as dengue, west-nile or bluetongue viruses. in seasonal environments, vector-borne disease occurrence varies with the seasonal variations of vector abundance. we aimed at understanding how diptera-borne viruses can persist for years under seasonal climates while vectors overwinter, which should stop pathogen transmission during winter. modeling is a relevant integrative approach for investigating the large panel of persisten ...201324023929
ten years of dengue drug discovery: progress and prospects.to combat neglected diseases, the novartis institute of tropical diseases (nitd) was founded in 2002 through private-public funding from novartis and the singapore economic development board. one of nitd's missions is to develop antivirals for dengue virus (denv), the most prevalent mosquito-borne viral pathogen. neither vaccine nor antiviral is currently available for denv. here we review the progress in dengue drug discovery made at nitd as well as the major discoveries made by academia and ot ...201324076358
favipiravir (t-705), a novel viral rna polymerase inhibitor.favipiravir (t-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an antiviral drug that selectively inhibits the rna-dependent rna polymerase of influenza virus. it is phosphoribosylated by cellular enzymes to its active form, favipiravir-ribofuranosyl-5'-triphosphate (rtp). its antiviral effect is attenuated by the addition of purine nucleic acids, indicating the viral rna polymerase mistakenly recognizes favipiravir-rtp as a purine nucleotide. favipiravir is active against a broad range of inf ...201324084488
distribution of mosquitoes in the south east of argentina and first report on the analysis based on 18s rdna and coi sequences.although mar del plata is the most important city on the atlantic coast of argentina, mosquitoes inhabiting such area are almost uncharacterized. to increase our knowledge in their distribution, we sampled specimens of natural populations. after the morphological identification based on taxonomic keys, sequences of dna from small ribosomal subunit (18s rdna) and cytochrome c oxidase i (coi) genes were obtained from native species and the phylogenetic analysis of these sequences were done. fourte ...201324098700
infectious bronchitis virus generates spherules from zippered endoplasmic reticulum membranes.replication of positive-sense rna viruses is associated with the rearrangement of cellular membranes. previous work on the infection of tissue culture cell lines with the betacoronaviruses mouse hepatitis virus and severe acute respiratory syndrome coronavirus (sars-cov) showed that they generate double-membrane vesicles (dmvs) and convoluted membranes as part of a reticular membrane network. here we describe a detailed study of the membrane rearrangements induced by the avian gammacoronavirus i ...201324149513
optimization of novel indole-2-carboxamide inhibitors of neurotropic alphavirus replication.neurotropic alphaviruses, which include western equine encephalitis virus (weev) and fort morgan virus, are mosquito-borne pathogens that infect the central nervous system causing acute and potentially fatal encephalitis. we previously reported a novel series of indole-2-carboxamides as alphavirus replication inhibitors, one of which conferred protection against neuroadapted sindbis virus infection in mice. we describe here further development of this series, resulting in 10-fold improvement in ...201324151954
liposome-antigen-nucleic acid complexes protect mice from lethal challenge with western and eastern equine encephalitis viruses.alphaviruses are mosquito-borne viruses that cause significant disease in animals and humans. western equine encephalitis virus (weev) and eastern equine encephalitis virus (eeev), two new world alphaviruses, can cause fatal encephalitis, and eeev is a select agent of concern in biodefense. however, we have no antiviral therapies against alphaviral disease, and current vaccine strategies target only a single alphavirus species. in an effort to develop new tools for a broader response to outbreak ...201324257615
isolation of saint louis encephalitis virus from a horse with neurological disease in brazil.st. louis encephalitis virus (slev) is a causative agent of encephalitis in humans in the western hemisphere. slev is a positive-sense rna virus that belongs to the flavivirus genus, which includes west nile encephalitis virus, japanese encephalitis virus, dengue virus and other medically important viruses. recently, we isolated a slev strain from the brain of a horse with neurological signs in the countryside of minas gerais, brazil. the slev isolation was confirmed by reverse-transcription rt- ...201324278489
a genome-wide analysis of rna pseudoknots that stimulate efficient -1 ribosomal frameshifting or readthrough in animal viruses.programmed -1 ribosomal frameshifting (prf) and stop codon readthrough are two translational recoding mechanisms utilized by some rna viruses to express their structural and enzymatic proteins at a defined ratio. efficient recoding usually requires an rna pseudoknot located several nucleotides downstream from the recoding site. to assess the strategic importance of the recoding pseudoknots, we have carried out a large scale genome-wide analysis in which we used an in-house developed program to d ...201324298557
west nile virus drug discovery.the outbreak of west nile virus (wnv) in 1999 in the usa, and its continued spread throughout the americas, parts of europe, the middle east and africa, underscored the need for wnv antiviral development. here, we review the current status of wnv drug discovery. a number of approaches have been used to search for inhibitors of wnv, including viral infection-based screening, enzyme-based screening, structure-based virtual screening, structure-based rationale design, and antibody-based therapy. th ...201324300672
discovery of potent broad spectrum antivirals derived from marine actinobacteria.natural products provide a vast array of chemical structures to explore in the discovery of new medicines. although secondary metabolites produced by microbes have been developed to treat a variety of diseases, including bacterial and fungal infections, to date there has been limited investigation of natural products with antiviral activity. in this report, we used a phenotypic cell-based replicon assay coupled with an iterative biochemical fractionation process to identify, purify, and characte ...201324349254
subgenomic reporter rna system for detection of alphavirus infection in mosquitoes.current methods for detecting real-time alphavirus (family togaviridae) infection in mosquitoes require the use of recombinant viruses engineered to express a visibly detectable reporter protein. these altered viruses expressing fluorescent proteins, usually from a duplicated viral subgenomic reporter, are effective at marking infection but tend to be attenuated due to the modification of the genome. additionally, field strains of viruses cannot be visualized using this approach unless infectiou ...201324367703
zoonotic encephalitides caused by arboviruses: transmission and epidemiology of alphaviruses and flaviviruses.in this review, we mainly focus on zoonotic encephalitides caused by arthropod-borne viruses (arboviruses) of the families flaviviridae (genus flavivirus) and togaviridae (genus alphavirus) that are important in both humans and domestic animals. specifically, we will focus on alphaviruses (eastern equine encephalitis virus, western equine encephalitis virus, venezuelan equine encephalitis virus) and flaviviruses (japanese encephalitis virus and west nile virus). most of these viruses were origin ...201324427764
human-like antibodies neutralizing western equine encephalitis virus.this study describes the development of the first neutralizing antibodies against western equine encephalitis virus (weev), a member of the genus alphavirus. weev is transmitted by mosquitoes and can spread to the human central nervous system, causing symptoms ranging from mild febrile reactions to life-threatening encephalitis. weev has been classified as a biological warfare agent by the us centers for disease control and prevention. no anti-weev drugs are currently commercially available. neu ...201424518197
seroepidemiology of selected alphaviruses and flaviviruses in bats in trinidad.a serosurvey of antibodies against selected flaviviruses and alphaviruses in 384 bats (representing 10 genera and 14 species) was conducted in the caribbean island of trinidad. sera were analysed using epitope-blocking enzyme-linked immunosorbent assays (elisas) specific for antibodies against west nile virus (wnv), venezuelan equine encephalitis virus (veev) and eastern equine encephalitis virus (eeev), all of which are zoonotic viruses of public health significance in the region. overall, the ...201524751420
a new insect cell glycoengineering approach provides baculovirus-inducible glycogene expression and increases human-type glycosylation efficiency.insect cells are often glycoengineered using dna constructs encoding foreign glyocoenzymes under the transcriptional control of the baculovirus immediate early promoter, ie1. however, we recently found that the delayed early baculovirus promoter, 39k, provides inducible and higher levels of transgene expression than ie1 after baculovirus infection (lin and jarvis, 2013). thus, the purpose of this study was to assess the utility of the 39k promoter for insect cell glycoengineering. we produced tw ...201424768688
western equine encephalitis virus: evolutionary analysis of a declining alphavirus based on complete genome sequences.western equine encephalitis virus (weev) is an arbovirus from the genus alphavirus, family togaviridae, which circulates in north america between birds and mosquitoes, occasionally causing disease in humans and equids. in recent decades, human infection has decreased dramatically; the last documented human case in north america occurred in 1994, and the virus has not been detected in mosquito pools since 2008. because limited information exists regarding the evolution of weev, we analyzed the ge ...201424899192
mosquitoes used to draw blood for arbovirus viremia determinations in small vertebrates.serial samples from the same individuals may be required for certain virological studies, however, some small animals cannot easily be blood-sampled. therefore, we evaluated the use of culex quinquefasciatus say and aedes albopictus skuse mosquitoes as "biological syringes" to draw blood for virus titer determinations in small vertebrates. groups of chicks (gallus gallus), hamsters (mesocricetus auratus), and house sparrows (passer domesticus) were experimentally infected with west nile virus (w ...201424901448
pyriproxyfen for mosquito control: female sterilization or horizontal transfer to oviposition substrates by anopheles gambiae sensu stricto and culex quinquefasciatus.the use of gravid mosquitoes as vehicles to auto-disseminate larvicides was recently demonstrated for the transfer of pyriproxyfen (ppf) by container-breeding aedes mosquitoes and presents an appealing idea to explore for other disease vectors. the success of this approach depends on the female's behaviour, the time of exposure and the amount of ppf that can be carried by an individual. we explore the effect of ppf exposure at seven time points around blood feeding on individual anopheles gambia ...201424954695
discovery of a novel compound with anti-venezuelan equine encephalitis virus activity that targets the nonstructural protein 2.alphaviruses present serious health threats as emerging and re-emerging viruses. venezuelan equine encephalitis virus (veev), a new world alphavirus, can cause encephalitis in humans and horses, but there are no therapeutics for treatment. to date, compounds reported as anti-veev or anti-alphavirus inhibitors have shown moderate activity. to discover new classes of anti-veev inhibitors with novel viral targets, we used a high-throughput screen based on the measurement of cell protection from liv ...201424967809
applications of in vivo imaging in the evaluation of the pathophysiology of viral and bacterial infections and in development of countermeasures to bsl3/4 pathogens.while preclinical and clinical imaging have been applied to drug discovery/development and characterization of disease pathology, few examples exist where imaging has been used to evaluate infectious agents or countermeasures to biosafety level (bsl)3/4 threat agents. viruses engineered with reporter constructs, i.e., enzymes and receptors, which are amenable to detection by positron emission tomography (pet), single photon emission tomography (spect), or magnetic resonance imaging (mri) have be ...201425008802
diagnosis of arboviruses using indirect sandwich igg elisa in horses from the brazilian amazon.the amazon as a whole is the largest reservoir of arboviruses worldwide, while the brazilian amazon hosts the largest variety of arboviruses isolated to date. in this study, the results of an indirect sandwich igg elisa, standardized for 19 arbovirustypes circulating among horses in brazilian amazon, were compared to results of the hemagglutination inhibition test. a screening test assessed the conditional probability distribution and a pearson linear correlation test determined the correlation ...201425013410
the equine encephalitides. 201425015497
novel indole-2-carboxamide compounds are potent broad-spectrum antivirals active against western equine encephalitis virus in vivo.neurotropic alphaviruses, including western, eastern, and venezuelan equine encephalitis viruses, cause serious and potentially fatal central nervous system infections in humans for which no currently approved therapies exist. we previously identified a series of thieno[3,2-b]pyrrole derivatives as novel inhibitors of neurotropic alphavirus replication, using a cell-based phenotypic assay (w. peng et al., j. infect. dis. 199:950-957, 2009, doi:http://dx.doi.org/10.1086/597275), and subsequently ...201425031353
confirmed viral meningitis with normal csf findings.an 18-year-old woman presented with a progressively worsening headache, photophobia feverishness and vomiting. three weeks previously she had returned to the uk from a trip to peru. at presentation, she had clinical signs of meningism. on admission, blood tests showed a mild lymphopenia, with a normal c reactive protein and white cell count. chest x-ray and ct of the head were normal. cerebrospinal fluid (csf) microscopy was normal. csf protein and glucose were in the normal range. mri of the he ...201425035443
field investigations of winter transmission of eastern equine encephalitis virus in florida.studies investigating winter transmission of eastern equine encephalitis virus (eeev) were conducted in hillsborough county, florida. the virus was detected in culiseta melanura and anopheles quadrimaculatus in february 2012 and 2013, respectively. during the winter months, herons were the most important avian hosts for all mosquito species encountered. in collections carried out in the summer of 2011, blood meals taken from herons were still common, but less frequently encountered than in winte ...201425070997
health assessment of wild lowland tapir (tapirus terrestris) populations in the atlantic forest and pantanal biomes, brazil (1996-2012).abstract the lowland tapir (tapirus terrestris) is found in south america and is listed as vulnerable to extinction by the international union for conservation of nature, red list of threatened species. health issues, particularly infectious diseases, are potential threats for the species. health information from 65 wild tapirs from two brazilian biomes, atlantic forest (af) and pantanal (pa), were collected during a long-term study (1996-2012). the study included physic, hematologic and biochem ...201425105810
combined alphavirus replicon particle vaccine induces durable and cross-protective immune responses against equine encephalitis viruses.alphavirus replicons were evaluated as potential vaccine candidates for venezuelan equine encephalitis virus (veev), western equine encephalitis virus (weev), or eastern equine encephalitis virus (eeev) when given individually or in combination (v/w/e) to mice or cynomolgus macaques. individual replicon vaccines or the combination v/w/e replicon vaccine elicited strong neutralizing antibodies in mice to their respective alphavirus. protection from either subcutaneous or aerosol challenge with ve ...201425122801
dynamics of midgut microflora and dengue virus impact on life history traits in aedes aegypti.significant morbidity and potential mortality following dengue virus infection is a re-emerging global health problem. due to the limited effectiveness of current disease control methods, mosquito biologists have been searching for new methods of controlling dengue transmission. while much effort has concentrated on determining genetic aspects to vector competence, paratransgenetic approaches could also uncover novel vector control strategies. the interactions of mosquito midgut microflora and p ...201425193134
emerging and reemerging neglected tropical diseases: a review of key characteristics, risk factors, and the policy and innovation environment.in global health, critical challenges have arisen from infectious diseases, including the emergence and reemergence of old and new infectious diseases. emergence and reemergence are accelerated by rapid human development, including numerous changes in demographics, populations, and the environment. this has also led to zoonoses in the changing human-animal ecosystem, which are impacted by a growing globalized society where pathogens do not recognize geopolitical borders. within this context, neg ...201425278579
differentiation of neurons restricts arbovirus replication and increases expression of the alpha isoform of irf-7.susceptibility to alphavirus infection is age dependent, and host maturation is associated with decreased virus replication and less severe encephalitis. to identify factors associated with maturation-dependent restriction of virus replication, we studied ap-7 rat olfactory bulb neuronal cells, which can differentiate in vitro. differentiation was associated with a 150- to 1,000-fold decrease in replication of the alphaviruses sindbis virus and venezuelan equine encephalitis virus, as well as la ...201425320290
chemokine receptors as important regulators of pathogenesis during arboviral encephalitis.the central nervous system (cns) is a highly complex network comprising long-lived neurons and glial cells. accordingly, numerous mechanisms have evolved to tightly regulate the initiation of inflammatory responses within the brain. under neuroinflammatory conditions, as in the case of viral encephalitides, the infiltration of leukocytes is often required for efficient viral clearance and recovery. the orchestration of leukocyte migration into the inflamed cns is largely coordinated by a large f ...201425324719
comparative study of the pathological effects of western equine encephalomyelitis virus in four strains of culex tarsalis coquillett (diptera: culicidae).early reports suggested that mosquito cells infected with arboviruses remain viable and undamaged. however, more recent experimental evidence suggests that arboviral infection of mosquito tissues might indeed result in pathological changes, with potential implications for vector survival and virus transmission. here, we compare the pathological effects of western equine encephalomyelitis virus (weev) infection in four strains of culex tarsalis previously reported to differ in their competence as ...201425346928
manipulation of host factors optimizes the pathogenesis of western equine encephalitis virus infections in mice for antiviral drug development.while alphaviruses spread naturally via mosquito vectors, some can also be transmitted as aerosols making them potential bioterrorism agents. one such pathogen, western equine encephalitis virus (weev), causes fatal human encephalitis via multiple routes of infection and thus presumably via multiple mechanisms. although weev also produces acute encephalitis in non-human primates, a small animal model that recapitulates features of human disease would be useful for both pathogenesis studies and t ...201425361697
liposomes as vaccine delivery systems: a review of the recent advances.liposomes and liposome-derived nanovesicles such as archaeosomes and virosomes have become important carrier systems in vaccine development and the interest for liposome-based vaccines has markedly increased. a key advantage of liposomes, archaeosomes and virosomes in general, and liposome-based vaccine delivery systems in particular, is their versatility and plasticity. liposome composition and preparation can be chosen to achieve desired features such as selection of lipid, charge, size, size ...201425364509
eilat virus host range restriction is present at multiple levels of the virus life cycle.most alphaviruses are mosquito-borne and exhibit a broad host range, infecting many different vertebrates, including birds, rodents, equids, humans, and nonhuman primates. this ability of most alphaviruses to infect arthropods and vertebrates is essential for their maintenance in nature. recently, a new alphavirus, eilat virus (eilv), was described, and in contrast to all other mosquito-borne viruses, it is unable to replicate in vertebrate cell lines. investigations into the nature of its host ...201425392227
evolutionary genetics and vector adaptation of recombinant viruses of the western equine encephalitis antigenic complex provides new insights into alphavirus diversity and host switching.western equine encephalitis virus (weev), highlands j virus (hjv), and fort morgan virus (fmv) are the sole representatives of the wee antigenic complex of the genus alphavirus, family togaviridae, that are endemic to north america. all three viruses have their ancestry in a recombination event involving eastern equine encephalitis virus (eeev) and a sindbis (sin)-like virus that gave rise to a chimeric alphavirus that subsequently diversified into the present-day weev, hjv, and fmv. here, we pr ...201425463613
arboviruses in north dakota, 2003-2006.to investigate arbovirus transmission in north dakota, we collected and screened mosquitoes for viral infection by vero cell culture assay. seven viruses were isolated from 13 mosquito species. spatial and temporal distributions of the important vectors of west nile virus (wnv), cache valley virus, jamestown canyon virus (jcv), and trivittatus virus are reported. snowshoe hare virus, potosi virus, and western equine encephalomyelitis virus were also isolated. the risks of culex tarsalis and aede ...201425487728
an inactivated ross river virus vaccine is well tolerated and immunogenic in an adult population in a randomized phase 3 trial.ross river virus (rrv) is endemic in australia and several south pacific islands. more than 90,000 cases of rrv disease, which is characterized by debilitating polyarthritis, were reported in australia in the last 20 years. there is no vaccine available to prevent rrv disease. a phase 3 study was undertaken at 17 sites in australia to investigate the safety and immunogenicity of an inactivated whole-virus vero cell culture-derived rrv vaccine in 1,755 healthy younger adults aged 16 to 59 years a ...201425540268
pediatric anti-nmda receptor encephalitis is seasonal.in the majority of pediatric anti-n-methyl-d-aspartate receptor encephalitis (nmdare) cases, the underlying cause of antibody production and subsequent disease remains unknown. we aimed to characterize this poorly understood population, investigating epidemiological factors potentially related to disease etiology, particularly season of onset. in this retrospective case review study, we analyzed data from the 29 pediatric subjects with anti-nmdar antibodies and found that symptoms were first rep ...201425540806
the combined use of alphavirus replicons and pseudoinfectious particles for the discovery of antivirals derived from natural products.alphaviruses are a prominent class of reemergent pathogens due to their globally expanding ranges, potential for lethality, and possible use as bioweapons. the absence of effective treatments for alphaviruses highlights the need for innovative strategies to identify antiviral agents. primary screens that use noninfectious self-replicating rnas, termed replicons, have been used to identify potential antiviral compounds for alphaviruses. only inhibitors of viral genome replication, however, will b ...201425550354
in- silico exploration of thirty alphavirus genomes for analysis of the simple sequence repeats.the compilation of simple sequence repeats (ssrs) in viruses and its analysis with reference to incidence, distribution and variation would be instrumental in understanding the functional and evolutionary aspects of repeat sequences. present study encompasses the analysis of ssrs across 30 species of alphaviruses. the full length genome sequences, assessed from ncbi were used for extraction and analysis of repeat sequences using imex software. the repeats of different motif sizes (mono- to penta ...201425606453
analysis of a pair of end+ and end- viruses derived from the same bovine viral diarrhea virus stock reveals the amino acid determinants in npro responsible for inhibition of type i interferon production.the exaltation of newcastle disease virus (end) phenomenon is induced by the inhibition of type i interferon in pestivirus-infected cells in vitro, via proteasomal degradation of cellular interferon regulatory factor (irf)-3 with the property of the viral autoprotease protein n(pro). reportedly, the amino acid residues in the zinc-binding trash motif of n(pro) determine the difference in characteristics between end-phenomenon-positive (end(+)) and end-phenomenon-negative (end(-)) classical swine ...201425648277
the ubiquitin proteasome system plays a role in venezuelan equine encephalitis virus infection.many viruses have been implicated in utilizing or modulating the ubiquitin proteasome system (ups) to enhance viral multiplication and/or to sustain a persistent infection. the mosquito-borne venezuelan equine encephalitis virus (veev) belongs to the togaviridae family and is an important biodefense pathogen and select agent. there are currently no approved vaccines or therapies for veev infections; therefore, it is imperative to identify novel targets for therapeutic development. we hypothesize ...201525927990
fatal west nile virus encephalitis in a heart transplant recipient.the diagnosis of encephalitis is particularly challenging in immunocompromised patients. we report here a case of fatal west nile virus encephalitis confounded by the presence of budding yeast in the cerebrospinal fluid (csf) from a patient who had undergone heart transplantation for dilated cardiomyopathy 11 months prior to presentation of neurologic symptoms.201525994169
type 1 interferon gene transfer enhances host defense against pulmonary streptococcus pneumoniae infection via activating innate leukocytes.pneumococcal infections are the leading cause of community-acquired pneumonia. although the type 1 interferon-α (ifn-α) is a well-known antiviral cytokine, the role of ifn-α in antipneumococcal host defense and its therapeutic potential remain poorly understood. we have investigated these issues by using a murine transgene expression model. we found that in control animals, streptococcus pneumoniae infection caused severe weight loss and excessive lung inflammation, associated with rapid bacteri ...201426015944
discovery of dengue virus ns4b inhibitors.the four serotypes of dengue virus (denv-1 to -4) represent the most prevalent mosquito-borne viral pathogens in humans. no clinically approved vaccine or antiviral is currently available for denv. here we report a spiropyrazolopyridone compound that potently inhibits denv both in vitro and in vivo. the inhibitor was identified through screening of a 1.8-million-compound library by using a denv-2 replicon assay. the compound selectively inhibits denv-2 and -3 (50% effective concentration [ec50], ...026018165
[establishment of a one-step real-time rt-pcr method for the detection of venezuelan equine encephalitis virus].venezuelan equine encephalitis (vee) is a zoonotic disease caused by the venezuelan equine encephalitis virus (veev) complex. this disease has not yet been reported in china, and it is therefore essential to establish a rapid and accurate method for detection of the virus in order to prevent and control this disease. in this study, a one-step real-time quantitative rt-pcr method was developed for the detection of the veev complex. a pair of specific primers and a taqman probe were designed corre ...201526164934
climate change, drought and human health in canada.droughts have been recorded all across canada and have had significant impacts on individuals and communities. with climate change, projections suggest an increasing risk of drought in canada, particularly in the south and interior. however, there has been little research on the impacts of drought on human health and the implications of a changing climate. a review of the canadian, u.s. and international literature relevant to the canadian context was conducted to better define these impacts and ...201526193300
divergent cerebrospinal fluid cytokine network induced by non-viral and different viral infections on the central nervous system.meningoencephalitis is one of the most common disorders of the central nervous system (cns) worldwide. viral meningoencephalitis differs from bacterial meningitis in several aspects. in some developing countries, bacterial meningitis has appropriate clinical management and chemotherapy is available. virus-associated and virus not detected meningoencephalitis are treatable, however, they may cause death in a few cases. the knowledge of how mediators of inflammation can induce disease would contri ...201526286516
the virus-host interplay: biogenesis of +rna replication complexes.positive-strand rna (+rna) viruses are an important group of human and animal pathogens that have significant global health and economic impacts. notable members include west nile virus, dengue virus, chikungunya, severe acute respiratory syndrome (sars) coronavirus and enteroviruses of the picornaviridae family.unfortunately, prophylactic and therapeutic treatments against these pathogens are limited. +rna viruses have limited coding capacity and thus rely extensively on host factors for succes ...201526287230
encephalitis surveillance through the emerging infections program, 1997-2010.encephalitis is a devastating illness that commonly causes neurologic disability and has a case fatality rate >5% in the united states. an etiologic agent is identified in <50% of cases, making diagnosis challenging. the centers for disease control and prevention emerging infections program (eip) encephalitis project established syndromic surveillance for encephalitis in new york, california, and tennessee, with the primary goal of increased identification of causative agents and secondary goals ...201526295485
multiplex qrt-pcr for the detection of western equine encephalomyelitis, st. louis encephalitis, and west nile viral rna in mosquito pools (diptera: culicidae).following the introduction of west nile virus into california during the summer of 2003, public health and vector control programs expanded surveillance efforts and were in need of diagnostics capable of rapid, sensitive, and specific detection of arbovirus infections of mosquitoes to inform decision support for intervention. development of a multiplex taqman or real-time semiquantitative reverse transcription polymerase chain reaction (rt-pcr) assay in which three virus specific primer-probe se ...201526334826
syndromic approach to arboviral diagnostics for global travelers as a basis for infectious disease surveillance.arboviruses have overlapping geographical distributions and can cause symptoms that coincide with more common infections. therefore, arbovirus infections are often neglected by travel diagnostics. here, we assessed the potential of syndrome-based approaches for diagnosis and surveillance of neglected arboviral diseases in returning travelers.201526372010
severe sepsis caused by california serogroup orthobunyavirus. 201526401906
development of human-like scfv-fc neutralizing botulinum neurotoxin e.botulinum neurotoxins (bonts) are considered to be the most toxic substances known on earth and are responsible for human botulism, a life-threatening disease characterized by flaccid muscle paralysis that occurs naturally by food-poisoning or colonization of the gastrointestinal tract by bont-producing clostridia. bonts have been classified as category a agent by the centers of disease control and prevention (cdc) and are listed among the six agents with the highest risk to be used as bioweapon ...201526440796
dissecting vectorial capacity for mosquito-borne viruses.the inter-relationship between mosquitoes and the viruses they transmit is complex. while previously understood barriers to infection and transmission remain valid, additional factors have been uncovered that suggest an 'arms race' between mosquito and virus. these include the mosquito microbiota and interplay between mosquito and viral genetics. following an infectious blood meal, the mosquito mounts an immune and transcriptional response, leading to altered expression of multiple genes. these ...201526569343
sindbis and middelburg old world alphaviruses associated with neurologic disease in horses, south africa.old world alphaviruses were identified in 52 of 623 horses with febrile or neurologic disease in south africa. five of 8 sindbis virus infections were mild; 2 of 3 fatal cases involved co-infections. of 44 middelburg virus infections, 28 caused neurologic disease; 12 were fatal. middelburg virus likely has zoonotic potential.026583836
single-cell analysis and stochastic modelling unveil large cell-to-cell variability in influenza a virus infection.biochemical reactions are subject to stochastic fluctuations that can give rise to cell-to-cell variability. yet, how this variability affects viral infections, which themselves involve noisy reactions, remains largely elusive. here we present single-cell experiments and stochastic simulations that reveal a large heterogeneity between influenza a virus (iav)-infected cells. in particular, experimental data show that progeny virus titres range from 1 to 970 plaque-forming units and intracellular ...201526586423
alphaviral equine encephalomyelitis (eastern, western and venezuelan).summary alphaviral equine encephalomyelitis is a mosquito-borne infection that causes severe neurological disease and fatalities in horses and humans in the americas. consequently, the equine alphaviruses (eastern, western and venezuelan) are of considerable concern worldwide and are notifiable to the world organisation for animal health. in addition, these diseases are considered a potent potential biological weapon, emphasising the need to develop an effective vaccine. alphaviral equine enceph ...201526601451
seroepidemiologic survey of potential pathogens in obligate and facultative scavenging avian species in california.throughout the world, populations of scavenger birds are declining rapidly with some populations already on the brink of extinction. much of the current research into the factors contributing to these declines has focused on exposure to drug residues, lead, and other toxins. despite increased monitoring of these declining populations, little is known about infectious diseases affecting scavenger bird species. to assess potential infectious disease risks to both obligate and facultative scavenger ...201526606755
neurotropic virus infections as the cause of immediate and delayed neuropathology.a wide range of viruses from different virus families in different geographical areas, may cause immediate or delayed neuropathological changes and neurological manifestations in humans and animals. infection by neurotropic viruses as well as the resulting immune response can irreversibly disrupt the complex structural and functional architecture of the central nervous system, frequently leaving the patient or affected animal with a poor or fatal prognosis. mechanisms that govern neuropathogenes ...201526659576
occurrence of antibodies anti -toxoplasma gondii, neospora caninum and leptospira interrogans in a captive deer herd in southern brazil.a large number of brazilian zoos keep many endangered species of deer, however, very few disease surveillance studies have been conducted among captive cervids. blood samples from 32 brazilian deer (blastocerus dichotomus, mazama nana and mazama americana) kept in captivity at bela vista biological sanctuary (foz do iguaçu, brazil) were investigated for 10 ruminant pathogens, with the aims of monitoring deer health status and evaluating any potential zoonotic risk. deer serum samples were tested ...201526689185
global emergence of alphaviruses that cause arthritis in humans.arthropod-borne viruses (arboviruses) may cause severe emerging and re-emerging infectious diseases, which pose a significant threat to human and animal health in the world today. these infectious diseases range from mild febrile illnesses, arthritis, and encephalitis to haemorrhagic fevers. it is postulated that certain environmental factors, vector competence, and host susceptibility have a major impact on the ecology of arboviral diseases. presently, there is a great interest in the emergence ...201526689654
surveillance for western equine encephalitis, st. louis encephalitis, and west nile viruses using reverse transcription loop-mediated isothermal amplification.collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. vector control districts in california routinely monitor for three human pathogenic viruses including west nile virus (wnv), western equine encephalitis virus (weev), and st. louis encephalitis virus (slev). reverse transcription quantitative polymerase chain reaction ...201626807734
wolbachia biocontrol strategies for arboviral diseases and the potential influence of resident wolbachia strains in mosquitoes.arboviruses transmitted by mosquitoes are a major cause of human disease worldwide. the absence of vaccines and effective vector control strategies has resulted in the need for novel mosquito control strategies. the endosymbiotic bacterium wolbachia has been proposed to form the basis for an effective mosquito biocontrol strategy. resident strains of wolbachia inhibit viral replication in drosophila fruit flies and induce a reproductive phenotype known as cytoplasmic incompatibility that allows ...201626925368
major emerging vector-borne zoonotic diseases of public health importance in canada.in canada, the emergence of vector-borne diseases may occur via international movement and subsequent establishment of vectors and pathogens, or via northward spread from endemic areas in the usa. re-emergence of endemic vector-borne diseases may occur due to climate-driven changes to their geographic range and ecology. lyme disease, west nile virus (wnv), and other vector-borne diseases were identified as priority emerging non-enteric zoonoses in canada in a prioritization exercise conducted by ...201526954882
surveys for antibodies against mosquitoborne encephalitis viruses in california birds, 1996-2013.from 1996 through 2013, 54,546 individual birds comprising 152 species and 7 orders were banded, bled, and released at four study areas within california, from which 28,388 additional serum samples were collected at one or more recapture encounters. of these, 142, 99, and 1929 birds from 41 species were positive for neutralizing antibodies against western equine encephalomyelitis virus (weev), st. louis encephalitis virus (slev), or west nile virus (wnv) at initial capture or recapture, respecti ...201626974395
wildlife trade and human health in lao pdr: an assessment of the zoonotic disease risk in markets.although the majority of emerging infectious diseases can be linked to wildlife sources, most pathogen spillover events to people could likely be avoided if transmission was better understood and practices adjusted to mitigate risk. wildlife trade can facilitate zoonotic disease transmission and represents a threat to human health and economies in asia, highlighted by the 2003 sars coronavirus outbreak, where a chinese wildlife market facilitated pathogen transmission. additionally, wildlife tra ...201627008628
molecular determinants of alphavirus neuropathogenesis in mice.alphaviruses are enveloped viruses with a positive-stranded rna genome, of the family togaviridae. in mammals and birds they are mosquito-transmitted and are of veterinary and medical importance. they cause primarily two types of disease: encephalitis and polyarthritis. here we review attempts to understand the molecular basis of encephalitis and virulence for the central nervous system (cns) in mouse models. sindbis virus (sinv) was the first virus to be studied in this way. other viruses analy ...201627028153
hierarchical cluster analysis of three-dimensional reconstructions of unbiased sampled microglia shows not continuous morphological changes from stage 1 to 2 after multiple dengue infections in callithrix penicillata.it is known that microglial morphology and function are related, but few studies have explored the subtleties of microglial morphological changes in response to specific pathogens. in the present report we quantitated microglia morphological changes in a monkey model of dengue disease with virus cns invasion. to mimic multiple infections that usually occur in endemic areas, where higher dengue infection incidence and abundant mosquito vectors carrying different serotypes coexist, subjects receiv ...201627047345
virus-specific thermostability and heat inactivation profiles of alphaviruses.serological diagnosis is a critical component for disease surveillance and is important to address the increase in incidence and disease burden of alphaviruses, such as the chikungunya (chikv) and ross river (rrv) viruses. the gold standard for serological diagnosis is the plaque reduction neutralization test (prnt), which demonstrates the neutralizing capacity of serum samples after the removal of complement activity and adventitious viruses. this procedure is normally performed following inact ...201627079828
vertical transmission of indian ocean lineage of chikungunya virus in aedes aegypti and aedes albopictus mosquitoes.the re-emergence of chikungunya (chik) fever in thailand has been caused by a novel lineage of chikungunya virus (chikv) termed the indian ocean lineage (iol). the aedes albopictus mosquito is thought to be a primary vector of chik fever in thailand, whereas ae. aegypti acts as a secondary vector of the virus. the vertical transmission is believed to be a primary means to maintain chikv in nature and may be associated with an increased risk of outbreak. therefore, the goal of this study was to a ...201627108077
culex tarsalis mosquitoes as vectors of highlands j virus.highlands j virus (hjv) is an alphavirus closely related to western equine encephalitis virus (weev) and eastern equine encephalitis virus (eeev). hjv is an avian pathogen with the potential for disruption of poultry operations, but is not known to cause human or equine disease. hjv has only been identified in the eastern united states and is thought to have a transmission cycle similar to that of eeev involving culiseta melanura mosquitoes and birds. however, hjv is more genetically similar to ...201627248005
combining reverse-transcription multiplex pcr and microfluidic electrophoresis to simultaneously detect seven mosquito-transmitted zoonotic encephalomyelitis viruses.several mosquito-transmitted viruses are causative agents for zoonotic encephalomyelitis. rapid identification of these viruses in mosquito populations is an effective method for surveying these diseases. to detect multiple mosquito-transmitted viral agents, including west nile virus, saint louis encephalitis virus, venezuelan equine encephalomyelitis virus, western equine encephalomyelitis virus, eastern equine encephalomyelitis virus, highlands j virus and japanese encephalitis virus, an assay ...201627256022
efficacy of t-705 (favipiravir) in the treatment of infections with lethal severe fever with thrombocytopenia syndrome virus.severe fever with thrombocytopenia syndrome virus (sftsv) is the causative agent of sfts, an emerging hemorrhagic fever. this disease has a high case fatality rate and is endemic to china, south korea, and japan. because there are currently no effective therapeutics for sfts, potent and safe antivirals are needed for the treatment of sfts. the inhibitory effect of t-705 (favipiravir) on the replication of sftsv in vero cells was evaluated. mice lacking the type i interferon receptor (ifnar(-/-)) ...201627303697
avian encephalomyelitis in layer pullets associated with vaccination.avian encephalomyelitis (ae) was diagnosed in three flocks of leghorn layer pullets following ae vaccination. ages of the birds were 11, 12, and 14 wk. the submissions came from three different companies located in two geographic areas of the central valley of california. the clinical signs included birds down on their legs, unilateral recumbency or sitting on their hocks, lethargy, reluctance to move, dehydration, unevenness in size, low weight, tremors of the head in a few birds, and mildly to ...201627309297
ethnopharmacological significance of eclipta alba (l.) hassk. (asteraceae).eclipta alba can be found growing wild in fallow lands of bangladesh where it is considered as a weed by farmers. traditional medicinal systems of the indian subcontinent countries as well as tribal practitioners consider the plant to have diverse medicinal values and use it commonly for treatment of gastrointestinal disorders, respiratory tract disorders (including asthma), fever, hair loss and graying of hair, liver disorders (including jaundice), skin disorders, spleen enlargement, and cuts a ...201427355071
neurological sequelae resulting from encephalitic alphavirus infection.the recent surge in viral clinical cases and associated neurological deficits have reminded us that viral infections can lead to detrimental, long-term effects, termed sequelae, in survivors. alphaviruses are enveloped, single-stranded positive-sense rna viruses in the togaviridae family. transmission of alphaviruses between and within species occurs mainly via the bite of an infected mosquito bite, giving alphaviruses a place among arboviruses, or arthropod-borne viruses. alphaviruses are found ...201627379085
alphavirus protease inhibitors from natural sources: a homology modeling and molecular docking investigation.alphaviruses such as chikungunya virus (chikv), o'nyong-nyong virus (onnv), ross river virus (rrv), eastern equine encephalitis virus (eeev), venezuelan equine encephalitis virus (veev), and western equine encephalitis virus (weev), are mosquito-transmitted viruses that can cause fevers, rash, and rheumatic diseases (chikv, onnv, rrv) or potentially fatal encephalitis (eeev, veev, weev) in humans. these diseases are considered neglected tropical diseases for which there are no current antiviral ...201627387412
evaluation of the vector competence of a native uk mosquito ochlerotatus detritus (aedes detritus) for dengue, chikungunya and west nile viruses.to date there has been no evidence of mosquito-borne virus transmission of public health concern in the uk, despite the occurrence of more than 30 species of mosquito, including putative vectors of arboviruses. the saltmarsh mosquito ochlerotatus detritus [syn. aedes (ochlerotatus) detritus] is locally common in parts of the uk where it can be a voracious feeder on people.201627527700
type-1 angiotensin receptor signaling in central nervous system myeloid cells is pathogenic during fatal alphavirus encephalitis in mice.alphaviruses can cause fatal encephalitis in humans. natural infections occur via the bite of infected mosquitos, but aerosol transmissibility makes some of these viruses potential bioterrorism agents. central nervous system (cns) host responses contribute to alphavirus pathogenesis in experimental models and are logical therapeutic targets. we investigated whether reactive oxygen species (ros) generated by nicotinamide adenine dinucleotide phosphate (nadph) oxidase (nox) activity within the cns ...201627562117
temporal variation in sindbis virus antibody prevalence in bird hosts in an endemic area in sweden.sindbis virus (sinv) is a mosquito-borne bird virus that occasionally causes human disease in fennoscandia, suggested to have cyclic 7-year intervals between outbreaks. reliable data on human infections in sweden is however lacking. here we investigated the sinv antibody prevalence among birds in a swedish area endemic to sinv to scrutinize if a cyclic variation in antibody prevalence is present in the natural host of sinv. serum from birds were sampled in the summers of 2002-2004 and 2009 in th ...201627579607
venezuelan and western equine encephalitis virus e1 liposome antigen nucleic acid complexes protect mice from lethal challenge with multiple alphaviruses.eastern, venezuelan and western equine encephalitis viruses (eeev, veev, and weev) are mosquito-borne viruses that cause substantial disease in humans and other vertebrates. vaccines are limited and current treatment options have not proven successful. in this report, we vaccinated outbred mice with lipid-antigen-nucleic acid-complexes (lanacs) containing veev e1+weev e1 antigen and characterized protective efficacy against lethal eeev, veev, and weev challenge. vaccination resulted in complete ...201627632563
molecular detection of flaviviruses and alphaviruses in mosquitoes (diptera: culicidae) from coastal ecosystems in the colombian caribbean.arboviruses belonging to the genera flavivirus and alphavirus were detected in mosquitoes in a rural area of san bernardo del viento (córdoba, colombia). a total of 22,180 mosquitoes were collected, sorted into 2,102 pools, and tested by generic/nested reverse transcription-polymerase chain reaction. venezuelan equine encephalitis virus, dengue virus, west nile virus, st. louis encephalitis virus, yellow fever virus, and culex flavivirus were detected and identified by sequencing. the detection ...201627706377
serosurveillance of viral pathogens circulating in west africa.sub-saharan africa is home to a variety of pathogens, but disease surveillance and the healthcare infrastructure necessary for proper management and control are severely limited. lassa virus, the cause of lassa fever, a severe hemorrhagic fever in humans is endemic in west africa. in sierra leone at the kenema government hospital lassa diagnostic laboratory, up to 70 % of acute patient samples suspected of lassa fever test negative for lassa virus infection. this large amount of acute undiagnose ...201627716429
experimental piscine alphavirus rna recombination in vivo yields both viable virus and defective viral rna.rna recombination in non-segmented rna viruses is important for viral evolution and documented for several virus species through in vitro studies. here we confirm viral rna recombination in vivo using an alphavirus, the sav3 subtype of salmon pancreas disease virus. the virus causes pancreas disease in atlantic salmon and heavy losses in european salmonid aquaculture. atlantic salmon were injected with a sav3 6k-gene deleted cdna plasmid, encoding a non-viable variant of sav3, together with a he ...201627805034
a universal next-generation sequencing protocol to generate noninfectious barcoded cdna libraries from high-containment rna viruses.several biosafety level 3 and/or 4 (bsl-3/4) pathogens are high-consequence, single-stranded rna viruses, and their genomes, when introduced into permissive cells, are infectious. moreover, many of these viruses are select agents (sas), and their genomes are also considered sas. for this reason, cdnas and/or their derivatives must be tested to ensure the absence of infectious virus and/or viral rna before transfer out of the bsl-3/4 and/or sa laboratory. this tremendously limits the capacity to ...201627822536
ablation of programmed -1 ribosomal frameshifting in venezuelan equine encephalitis virus results in attenuated neuropathogenicity.the alphaviruses venezuelan equine encephalitis virus (veev), eastern equine encephalitis virus (eeev), and western equine encephalitis virus (weev) are arthropod-borne positive-strand rna viruses that are capable of causing acute and fatal encephalitis in many mammals, including humans. veev was weaponized during the cold war and is recognized as a select agent. currently, there are no fda-approved vaccines or therapeutics for these viruses. the spread of veev and other members of this family d ...201727852852
notice to readers: final 2015 reports of nationally notifiable infectious diseases and conditions.the table listed in this report on pages 1307-1321 presents finalized data, as of june 30, 2016, from the national notifiable diseases surveillance system (nndss) for 2015. these data will be published in more detail in the summary of notifiable infectious diseases and conditions - united states, 2015 (1). because no cases were reported in the united states during 2015, the following diseases do not appear in this early release table: anthrax; dengue hemorrhagic fever; diphtheria; eastern equine ...201627880744
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