evaluation of the langat/dengue 4 chimeric virus as a live attenuated tick-borne encephalitis vaccine for safety and immunogenicity in healthy adult volunteers.with the steady rise in tick-borne encephalitis virus (tbev) infections in europe, development of a live attenuated vaccine that will generate long-lasting immunity would be of considerable benefit. a chimeric flavivirus, designated lgt/den4, was previously constructed to have a genome containing the prm and e protein genes of langat virus (lgt), a naturally attenuated member of the tbev complex, and the remaining genetic sequences derived from dengue 4 virus (den4). lgt/den4 was highly attenuat ...200818207289
novel variant of tickborne encephalitis virus, russia.we isolated a novel strain of tickborne encephalitis virus (tbev), glubinnoe/2004, from a patient with a fatal case in russia. we sequenced the strain, whose landmark features included 57 amino acid substitutions and 5 modified cleavage sites. phylogenetically, glubinnoe/2004 is a novel variant that belongs to the eastern type of tbev.200718258012
enzyme-linked immunosorbent assays using novel japanese encephalitis virus antigen improve the accuracy of clinical diagnosis of flavivirus infections.the cross-reactive antibodies induced by flavivirus infections confound serodiagnosis and pathogenesis, especially in secondary infections caused by antigenically closely related yet distinct flaviviruses. the envelope (e) glycoprotein fusion peptide contains immunodominant cross-reactive determinants. using a recombinant japanese encephalitis virus (jev) premembrane and e expression plasmid producing jev virus-like particles (vlps), dramatic reductions in cross-reactivity were produced by the g ...200818337381
land use and west nile virus seroprevalence in wild mammals.we examined west nile virus (wnv) seroprevalence in wild mammals along a forest-to-urban gradient in the us mid-atlantic region. wnv antibody prevalence increased with age, urbanization, and date of capture for juveniles and varied significantly between species. these findings suggest several requirements for using mammals as indicators of transmission.200818507915
flavivirus methyltransferase: a novel antiviral target.many flaviviruses are significant human pathogens. no effective antiviral therapy is currently available for treatment of flavivirus infections. development of antiviral treatment against these viruses is urgently needed. the flavivirus methyltransferase (mtase) responsible for n-7 and 2'-o methylation of the viral rna cap has recently been mapped to the n-terminal region of nonstructural protein 5. structural and functional studies suggest that the mtase represents a novel antiviral target. her ...200818571739
north american encephalitic arboviruses.arboviruses continue to be a major cause of encephalitis in north america, and west nile virus neuroinvasive disease is now the dominant cause of encephalitis. transmission to humans of north american arboviruses occurs by infected mosquitoes or ticks. most infections are asymptomatic or produce a flulike illness. rapid serum or cerebrospinal fluid igm antibody capture elisa assays are available to diagnosis the acute infection for all north american arboviruses. unfortunately, no antiviral drug ...200818657724
a complex rna motif defined by three discontinuous 5-nucleotide-long strands is essential for flavivirus rna replication.tertiary or higher-order rna motifs that regulate replication of positive-strand rna viruses are as yet poorly understood. using japanese encephalitis virus (jev), we now show that a key element in jev rna replication is a complex rna motif that includes a string of three discontinuous complementary sequences (tdcs). the tdcs consists of three 5-nt-long strands, the left (l) strand upstream of the translation initiator aug adjacent to the 5'-end of the genome, and the middle (m) and right (r) st ...200818669441
genetic and serologic properties of zika virus associated with an epidemic, yap state, micronesia, 2007.zika virus (zikv) is a mosquito-borne flavivirus first isolated in uganda from a sentinel monkey in 1947. mosquito and sentinel animal surveillance studies have demonstrated that zikv is endemic to africa and southeast asia, yet reported human cases are rare, with <10 cases reported in the literature. in june 2007, an epidemic of fever and rash associated with zikv was detected in yap state, federated states of micronesia. we report the genetic and serologic properties of the zikv associated wit ...200818680646
detection and serotyping of dengue virus in serum samples by multiplex reverse transcriptase pcr-ligase detection reaction assay.the detection and successful typing of dengue virus (denv) from patients with suspected dengue fever is important both for the diagnosis of the disease and for the implementation of epidemiologic control measures. a technique for the multiplex detection and typing of denv serotypes 1 to 4 (denv-1 to denv-4) from clinical samples by pcr-ligase detection reaction (ldr) has been developed. a serotype-specific pcr amplifies the regions of genes c and e simultaneously. the two amplicons are targeted ...200818685000
serum antibodies to west nile virus in naturally exposed and vaccinated horses.a polyvalent elisa and plaque reduction neutralization tests (prnts) were used to measure serum antibodies to west nile virus (wnv) in horses naturally exposed to or vaccinated against this flavivirus in connecticut and new york state, usa. relying on a prnt as a 'gold standard', the main objective was to validate a modified elisa containing a recombinant wnv envelope protein antigen. it was also important to assess specificity by testing sera from horses that had other, undiagnosed illnesses. s ...200818719177
powassan encephalitis and colorado tick fever.this article discusses two tick-borne illnesses: powassan encephalitis, a rare cause of central nervous system infection caused by the powassan virus, and colorado tick fever, an acute febrile illness caused by the colorado tick fever virus common to the rocky mountain region of north america.200818755390
experimental infection of eastern gray squirrels (sciurus carolinensis) with west nile virus.eastern gray squirrels (sciurus carolinensis) have shown high west nile virus (wnv) seroprevalence, and wnv infection has been suggested as a cause of morbidity and mortality in this species. we experimentally infected nine eastern gray squirrels with wnv to determine the clinical effects of infection and to assess their potential role as amplifying hosts. we observed no morbidity or mortality attributable to wnv infection, but lesions were apparent in several organs. we detected mean viremias o ...200818784241
impact of climate change and other factors on emerging arbovirus diseases.while some skeptics remain unconvinced that global climate change is a reality, there is no doubt that during the past 50 years or so, patterns of emerging arbovirus diseases have changed significantly. can this be attributed to climate change? climate is a major factor in determining: (1) the geographic and temporal distribution of arthropods; (2) characteristics of arthropod life cycles; (3) dispersal patterns of associated arboviruses; (4) the evolution of arboviruses; and (5) the efficiency ...200918799177
identification of genetic determinants of a tick-borne flavivirus associated with host-specific adaptation and pathogenicity.tick-borne flaviviruses are maintained in nature in an enzootic cycle involving a tick vector and a vertebrate host. thus, the virus replicates in two disparate hosts, each providing selective pressures that can influence virus replication and pathogenicity. to identify viral determinants associated with replication in the individual hosts, plaque purified langat virus (tp21pp) was adapted to growth in mouse or tick cell lines to generate two virus variants, mnbp20 and isep20, respectively. viru ...200818823640
increased recognition of powassan encephalitis in the united states, 1999-2005.powassan virus (powv) disease is a rare human disease caused by a tick-borne encephalitis group flavivirus maintained in a transmission cycle between ixodes cookei and other ixodid ticks and small and medium-sized mammals. during 1958-1998, only 27 powv disease cases (mostly powassan encephalitis) were reported from eastern canada and the northeastern united states (average, 0.7 cases per year). during 1999-2005, nine cases (described herein) of serologically confirmed powv disease were reported ...200818959500
stable prevalence of powassan virus in ixodes scapularis in a northern wisconsin focus.deer tick virus (dtv), a variant of powassan virus (powv), appears to be maintained in nature in an enzootic cycle between ixodes scapularis ticks and small mammals. although powv infection of human beings is rare, a recent report suggests increasing incidence and the possibility that powv may be an emerging tick-borne zoonosis. therefore, we assessed the long-term stability of the powv transmission cycle in northwestern wisconsin. adult i. scapularis and dermacentor variabilis were collected fr ...200819052313
isolation of kyasanur forest disease virus from febrile patient, yunnan, china.we recently determined that nanjianyin virus, isolated from serum of a patient in yunnan province, china, in 1989, is a type of kyasanur forest disease virus. results of a 1987-1990 seroepidemiologic investigation in yunnan province had shown that residents of the hengduan mountain region had been infected with nanjianyin virus.200919193286
development of a human-murine chimeric immunoglobulin m antibody for use in the serological detection of human flavivirus antibodies.current diagnosis of human flaviviral infections relies heavily on serological techniques such as the immunoglobulin m (igm) antibody capture enzyme-linked immunosorbent assay (mac-elisa). broad application of this assay is hindered by a lack of standardized human positive-control sera that react with the wide variety of flaviviruses that can cause human disease, e.g., dengue virus (denv), west nile virus (wnv), yellow fever virus (yfv), japanese encephalitis virus (jev), and st. louis encephali ...200919297614
characterization of powassan viruses from far eastern russia.we report the isolation and detailed characterization of the novel strain, partizansk/2006, of powassan virus (powv) from a human case of infection, which occurred in primorsky krai, russia, in 2006. comparative complete genome sequence analysis of the far eastern strains spassk-9 (1975), nadezdinsk-1991 and partizansk/2006 of powv revealed that these strains are 99.8% similar to the lb strain, which was isolated in canada in 1958. phylogenetic analysis of 5' utr sequences of five other strains ...200919363586
fatal case of deer tick virus encephalitis.deer tick virus is related to powassan virus, a tickborne encephalitis virus. a 62-year-old man presented with a meningoencephalitis syndrome and eventually died. analyses of tissue samples obtained during surgery and at autopsy revealed a widespread necrotizing meningoencephalitis. nucleic acid was extracted from formalin-fixed tissue, and the presence of deer tick virus was verified on a flavivirus-specific polymerase-chain-reaction (pcr) assay, followed by sequence confirmation. immunohistoch ...200919439744
virus-host coevolution: common patterns of nucleotide motif usage in flaviviridae and their hosts.virus-host biological interaction is a continuous coevolutionary process involving both host immune system and viral escape mechanisms. flaviviridae family is composed of fast evolving rna viruses that infects vertebrate (mammals and birds) and/or invertebrate (ticks and mosquitoes) organisms. these host groups are very distinct life forms separated by a long evolutionary time, so lineage-specific anti-viral mechanisms are likely to have evolved. flaviviridae viruses which infect a single host l ...200919617912
assessment of polymicrobial infections in ticks in new york state.ixodes scapularis ticks are clinically important hematophagous vectors. a single tick bite can lead to a polymicrobial infection. we determined the prevalence of polymicrobial infection with borrelia burgdorferi, anaplasma phagocytophilum, babesia microti, borrelia miyamotoi, and powassan virus in 286 adult ticks from the two counties in new york state where lyme disease is endemic, utilizing a masstag multiplex polymerase chain reaction assay. seventy-one percent of the ticks harbored at least ...201019725770
blood feeding by the rocky mountain spotted fever vector, dermacentor andersoni, induces interleukin-4 expression by cognate antigen responding cd4+ t cells.abstract:200919814808
an adenosine nucleoside inhibitor of dengue virus.dengue virus (denv), a mosquito-borne flavivirus, is a major public health threat. the virus poses risk to 2.5 billion people worldwide and causes 50 to 100 million human infections each year. neither a vaccine nor an antiviral therapy is currently available for prevention and treatment of denv infection. here, we report a previously undescribed adenosine analog, nitd008, that potently inhibits denv both in vitro and in vivo. in addition to the 4 serotypes of denv, nitd008 inhibits other flavivi ...200919918064
structure and functionality in flavivirus ns-proteins: perspectives for drug design.flaviviridae are small enveloped viruses hosting a positive-sense single-stranded rna genome. besides yellow fever virus, a landmark case in the history of virology, members of the flavivirus genus, such as west nile virus and dengue virus, are increasingly gaining attention due to their re-emergence and incidence in different areas of the world. additional environmental and demographic considerations suggest that novel or known flaviviruses will continue to emerge in the future. nevertheless, u ...201019945487
[genetic diversity of ixodid tick-borne pathogens in tomsk city and suburbs].we studied two urban and two suburban biotypes of tomsk city for tick-transmitted diseases prevalence in naturally collected ticks. tick-borne encephalitis virus (tbev) was found in 6.5% of tick samples, west nile virus (wnv) in 2.2%, borrelia spp. in 8%, rickettsia spp. in 2.5%, and ehrlichia spp. in 1.7% of samples. genetic markers of powassan virus, bartonella spp., and balbesia spp. were not found. analysis of the genetic diversity of revealed pathogens resulted in the following conclusions: ...200919957906
update on powassan virus: emergence of a north american tick-borne flavivirus.powassan virus (pow) (flaviviridae: flavivirus) is the cause of rare but severe neuroinvasive disease in north america and russia. the virus is transmitted among small- and medium-sized mammals by ixodid ticks. human infections occur via spillover from the main transmission cycle(s). since the late 1990s, the incidence of human disease seems to be increasing. in addition, pow constitutes a genetically diverse group of virus genotypes, including deer tick virus, that are maintained in distinct en ...201019961325
pcp consensus sequences of flaviviruses: correlating variance with vector competence and disease phenotype.computational methods are needed to design multivalent vaccines against flaviviruses (fvs) such as the west nile virus or the dengue virus (denv).201019969003
environmental health indicators of climate change for the united states: findings from the state environmental health indicator develop public health adaptation strategies and to project the impacts of climate change on human health, indicators of vulnerability and preparedness along with accurate surveillance data on climate-sensitive health outcomes are needed. we researched and developed environmental health indicators for inputs into human health vulnerability assessments for climate change and to propose public health preventative actions.200920049116
extraction of total nucleic acids from ticks for the detection of bacterial and viral pathogens.ticks harbor numerous bacterial, protozoal, and viral pathogens that can cause serious infections in humans and domestic animals. active surveillance of the tick vector can provide insight into the frequency and distribution of important pathogens in the environment. nucleic-acid based detection of tick-borne bacterial, protozoan, and viral pathogens requires the extraction of both dna and rna (total nucleic acids) from ticks. traditional methods for nucleic acid extraction are limited to extrac ...201020180313
tick-borne encephalitis among u.s. travelers to europe and asia - 2000-2009.tick-borne encephalitis virus (tbev) is the most common arbovirus transmitted by ticks in europe. approximately 10,000 cases of tick-borne encephalitis (tbe) are reported annually in europe and russia. although tbe is endemic in parts of china, information regarding its incidence is limited. tbev is closely related to powassan virus (powv), another tick-borne flavivirus that is a rare cause of encephalitis in north america and russia; tbev and powv can cross-react in serologic tests. before 2000 ...201020339345
emergence of zoonotic arboviruses by animal trade and migration.abstract: arboviruses are transmitted in nature exclusively or to a major extend by arthropods. they belong to the most important viruses invading new areas in the world and their occurrence is strongly influenced by climatic changes due to the life cycle of the transmitting vectors. several arboviruses have emerged in new regions of the world during the last years, like west nile virus (wnv) in the americas, usutu virus (usuv) in central europe, or rift valley fever virus (rvfv) in the arabian ...201020377873
rapid identification of vector-borne flaviviruses by mass spectrometry.flaviviruses are a highly diverse group of rna viruses classified within the genus flavivirus, family flaviviridae. most flaviviruses are arthropod-borne, requiring a mosquito or tick vector. several flaviviruses are highly pathogenic to humans; however, their high genetic diversity and immunological relatedness makes them extremely challenging to diagnose. in this study, we developed and evaluated a broad-range flavivirus assay designed to detect both tick- and mosquito-borne flaviviruses by us ...201020412852
deciphering the molecular basis for nucleotide selection by the west nile virus rna helicase.the west nile virus rna helicase uses the energy derived from the hydrolysis of nucleotides to separate complementary strands of rna. although this enzyme has a preference for atp, the bias towards this purine nucleotide cannot be explained on the basis of specific protein-atp interactions. moreover, the enzyme does not harbor the characteristic q-motif found in other helicases that regulates binding to atp. in the present study, we used structural homology modeling to generate a model of the we ...201020421212
homogeneity of powassan virus populations in naturally infected ixodes scapularis.powassan virus (powv, flaviviridae: flavivirus) is the sole north american member of the tick-borne encephalitis complex and consists of two distinct lineages that are maintained in ecologically discrete enzootic transmission cycles. the underlying genetic mechanisms that lead to niche partitioning in arboviruses are poorly understood. therefore, intra- and interhost genetic diversity was analyzed to determine if powv exists as a quasispecies in nature and quantify selective pressures within and ...201020434750
the neglected arboviral infections in mainland china.the major arboviral diseases in mainland china include japanese encephalitis, dengue fever, crimean-congo hemorrhagic fever (also known as xinjiang hemorrhagic fever), and tick-borne encephalitis. these and other newly found arbovirus infections due to banna virus and tahyna virus contribute to a large and relatively neglected disease burden in china. here we briefly review the literature regarding these arboviral infections in mainland china with emphasis on their epidemiology, primary vectors, ...201020436960
tickborne powassan virus infections among wisconsin residents.powassan virus (powv) is a tickborne flavivirus that causes a rare but potentially life-threatening illness. the first reported case of powv infection in a wisconsin resident occurred in 2003. enhanced surveillance and testing detected 2 additional cases.201020443328
high-throughput procedure for tick surveys of tick-borne encephalitis virus and its application in a national surveillance study in switzerland.tick-borne encephalitis (tbe), a viral infection of the central nervous system, is endemic in many eurasian countries. in switzerland, tbe risk areas have been characterized by geographic mapping of clinical cases. since mass vaccination should significantly decrease the number of tbe cases, alternative methods for exposure risk assessment are required. we established a new pcr-based test for the detection of tbe virus (tbev) in ticks. the protocol involves an automated, high-throughput nucleic ...201020453126
bioinformatics in new generation flavivirus vaccines.flavivirus infections are the most prevalent arthropod-borne infections world wide, often causing severe disease especially among children, the elderly, and the immunocompromised. in the absence of effective antiviral treatment, prevention through vaccination would greatly reduce morbidity and mortality associated with flavivirus infections. despite the success of the empirically developed vaccines against yellow fever virus, japanese encephalitis virus and tick-borne encephalitis virus, there i ...201020467477
tick-borne flaviviruses.there has been a remarkable increase in tick-borne flaviviral disease incidence throughout the past 2 decades. transmission of tick-borne viruses, like other vector-borne agents, is impacted by a very broad set of factors, both natural (eg, climate and ecology) and man-made (eg, human mobility and agricultural patterns). as our encroachment into areas of virus endemicity intensifies, and as changes in global economic and environmental conditions continue to promote the expansion of tick populati ...201020513549
quantum of infection of francisella tularensis tularensis in host-seeking dermacentor variabilis.the american dog tick, dermacentor variabilis, is fundamental to the perpetuation of francisella tularensis tularensis on martha's vineyard, massachusetts, u.s.a. although infected ticks are relatively common on the island, human cases deriving from tick bite are rare. it may be that the quantum of bacteria within these naturally infected ticks is frequently too small to cause disease. accordingly, we quantified the amount of f.t. tularensis bacteria in host-seeking ticks from the island. contra ...201020563231
characterization of dengue virus resistance to brequinar in cell culture.brequinar is an inhibitor of dihydroorotate dehydrogenase, an enzyme that is required for de novo pyrimidine biosynthesis. here we report that brequinar has activity against a broad spectrum of viruses. the compound not only inhibits flaviviruses (dengue virus, west nile virus, yellow fever virus, and powassan virus) but also suppresses a plus-strand rna alphavirus (western equine encephalitis virus) and a negative-strand rna rhabdovirus (vesicular stomatitis virus). using dengue virus serotype ...201020606073
molecular epidemiology of powassan virus in north america.powassan virus (pow) is a tick-borne flavivirus distributed in canada, the northern usa and the primorsky region of russia. pow is the only tick-borne flavivirus endemic to the western hemisphere, where it is transmitted mainly between ixodes cookei and groundhogs (marmota monax). deer tick virus (dtv), a genotype of pow that has been frequently isolated from deer ticks (ixodes scapularis), appears to be maintained in an enzootic cycle between these ticks and white-footed mice (peromyscus leucop ...201020631087
persistence of pathogens with short infectious periods in seasonal tick populations: the relative importance of three transmission routes.the flaviviruses causing tick-borne encephalitis (tbe) persist at low but consistent levels in tick populations, despite short infectious periods in their mammalian hosts and transmission periods constrained by distinctly seasonal tick life cycles. in addition to systemic and vertical transmission, cofeeding transmission has been proposed as an important route for the persistence of tbe-causing viruses. because cofeeding transmission requires ticks to feed simultaneously, the timing of tick acti ...201020668521
structural and functional analyses of a conserved hydrophobic pocket of flavivirus methyltransferase.the flavivirus methyltransferase (mtase) sequentially methylates the n7 and 2'-o positions of the viral rna cap (gpppa-rna → m(7)gpppa-rna → m(7)gpppam-rna), using s-adenosyl-l-methionine (adomet) as a methyl donor. we report here that sinefungin (sin), an adomet analog, inhibits several flaviviruses through suppression of viral mtase. the crystal structure of west nile virus mtase in complex with sin inhibitor at 2.0-å resolution revealed a flavivirus-conserved hydrophobic pocket located next t ...201020685660
prevalence of tick-borne encephalitis virus in ticks from southern korea.the prevalence of tick-borne encephalitis virus (tbev) in southern korea was determined by collecting ticks using tick drags. a total of 4,077 of 6,788 ticks collected were pooled (649 pools) according to collection site, species, and developmental stage and assayed for tbev. the tbev protein e and ns5 gene fragments were detected using rt-nested pcr in six pools of nymphs collected from jeju island (2,491 ticks). the minimum field detection rates for tbev were 0.17% and 0.14% for haemaphysalis ...201020706026
development of human-murine chimeric immunoglobulin g for use in the serological detection of human flavivirus and alphavirus antibodies.diagnosis of human arboviral infections relies heavily on serological techniques such as the immunoglobulin m (igm) antibody capture enzyme-linked immunosorbent assay (mac-elisa) and the indirect igg elisa. broad application of these assays is hindered by the lack of standardized positive human control sera that react with a wide variety of flaviviruses (e.g., dengue, west nile, yellow fever, japanese encephalitis, saint louis encephalitis, and powassan viruses), or alphaviruses (e.g., eastern e ...201020739503
human granulocytic anaplasmosis: first reported case in canada.human granulocytic anaplasmosis (hga) is a tick-borne rickettsial infection of peripheral blood neutrophils caused by anaplasma phagocytophilum. while this infection is increasingly recognized as endemic throughout much of the united states, no canadian cases have been previously described, despite the agent being identified in canadian ticks. herein we present a case of hga acquired in an urban alberta centre. canadian physicians must be aware of the possibility of tick-borne rickettsial diseas ...200920808448
loop analysis for pathogens: niche partitioning in the transmission graph for pathogens of the north american tick ixodes population biology, loop analysis is a method of decomposing a life cycle graph into life history pathways so as to compare the relative contributions of pathways to the population growth rate across species and populations. we apply loop analysis to the transmission graph of five pathogens known to infect the black-legged tick, ixodes scapularis. in this context loops represent repeating chains of transmission that could maintain the pathogen. they hence represent completions of the life cyc ...201020950628
tick histamine release factor is critical for ixodes scapularis engorgement and transmission of the lyme disease agent.ticks are distributed worldwide and affect human and animal health by transmitting diverse infectious agents. effective vaccines against most tick-borne pathogens are not currently available. in this study, we characterized a tick histamine release factor (thrf) from ixodes scapularis and addressed the vaccine potential of this antigen in the context of tick engorgement and b. burgdorferi transmission. results from western blotting and quantitative reverse transcription-pcr showed that thrf is s ...201021124826
pathogen-pathogen interaction: a syndemic model of complex biosocial processes in disease.there is growing awareness of the health implications of fact that infectious agents often do not act independently; rather their disease potential is mediated in diverse and significant ways by their relationships with other pathogens. pathogen-pathogen interaction (ppi), for example, impacts various virulence factors in human infection. although still in its infancy, the study of ppi, a form of epidemiological synergism, is emerging as an important arena of new research and new understanding i ...201021178409
evidence of simultaneous circulation of west nile and usutu viruses in mosquitoes sampled in emilia-romagna region (italy) in recent years human diseases due to mosquito-borne viruses were increasingly reported in emilia-romagna region (italy), from the chikungunya virus in 2007 to the west nile virus (wnv) in 2008. an extensive entomological survey was performed in 2009 to establish the presence and distribution of mosquito arboviruses in this region, with particular reference to flaviviruses.201021179462
the unique transmembrane hairpin of flavivirus fusion protein e is essential for membrane fusion.the fusion of enveloped viruses with cellular membranes is mediated by proteins that are anchored in the lipid bilayer of the virus and capable of triggered conformational changes necessary for driving fusion. the flavivirus envelope protein e is the only known viral fusion protein with a double membrane anchor, consisting of two antiparallel transmembrane helices (tm1 and tm2). tm1 functions as a stop-transfer sequence and tm2 as an internal signal sequence for the first nonstructural protein d ...201121325407
evaluation of widely used diagnostic tests to detect west nile virus infections in horses previously infected with st. louis encephalitis virus or dengue virus type 2.primary west nile virus (wnv) infections can be diagnosed using a number of tests that detect infectious particles, nucleic acid, and specific igm and/or igg antibodies. however, serological identification of the infecting agent in secondary or subsequent flavivirus infections is problematic due to the extensive cross-reactivity of flavivirus antibodies. this is particularly difficult in the tropical americas where multiple flaviviruses cocirculate. a study of sequential flavivirus infection in ...201121346058
tick-borne encephalitis virus in dogs - is this an issue?abstract: the last review on tick-borne encephalitis (tbe) in dogs was published almost ten years ago. since then, this zoonotic tick-borne arbovirus has been geographically spreading and emerging in many regions in eurasia and continues to do so. dogs become readily infected with tbe virus but they are accidental hosts not capable to further spread the virus. they seroconvert upon infection but they seem to be much more resistant to the clinical disease than humans. apart from their use as sent ...201121489255
a snapshot of the ixodes scapularis degradome.parasitic encoded proteases are essential to regulating interactions between parasites and their hosts and thus they represent attractive anti-parasitic druggable and/or vaccine target. we have utilized annotations of ixodes scapularis proteases in gene bank and version 9.3 merops database to compile an index of at least 233 putatively active and 150 putatively inactive protease enzymes that are encoded by the i. scapularis genome. the 233 putatively active protease homologs hereafter referred t ...201121596113
mutational analysis of three predicted 5'-proximal stem-loop structures in the genome of tick-borne encephalitis virus indicates different roles in rna replication and translation.flavivirus gene expression is modulated by rna secondary structure elements at the terminal ends of the viral rna molecule. for tick-borne encephalitis virus (tbev), four stem-loop (sl) elements have been predicted in the first 180 nucleotides of the viral genome: 5'-sl1, 5'-sl2, 5'-sl3 and 5'-sl4. the last three of these appear to be unique to tick-borne flaviviruses. here, we report their characterization by mutagenesis in a tbev luciferase reporter system. by manipulating their thermodynamic ...201121645915
west nile virus disease and other arboviral diseases --- united states, 2010.arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. since west nile virus (wnv) was first detected in the western hemisphere in 1999, it has become the leading cause of neuroinvasive arboviral disease in the united states. however, several other arboviruses continue to cause sporadic cases and seasonal outbreaks of neuroinvasive disease (i.e., meningitis, encephalitis, or acute flaccid paralysis). this report summarizes su ...201121814163
requirement of glycosylation of west nile virus envelope protein for infection of, but not spread within, culex quinquefasciatus mosquito vectors.abstract. most of sequenced west nile virus (wnv) genomes encode a single n-linked glycosylation site on their envelope (e) proteins. we previously found that wnv lacking the e protein glycan was severely inhibited in its ability to replicate and spread within two important mosquito vector species, culex pipiens and cx. tarsalis. however, recent work with a closely related species, cx. pipiens pallens, found no association between e protein glycosylation and either replication or dissemination. ...201121813861
genotype v japanese encephalitis virus is emerging.japanese encephalitis (je) is a global public health issue that has spread widely to more than 20 countries in asia and has extended its geographic range to the south pacific region including australia. je has become the most important cause of viral encephalitis in the world. japanese encephalitis viruses (jev) are divided into five genotypes, based on the nucleotide sequence of the envelope (e) gene. the muar strain, isolated from patient in malaya in 1952, is the sole example of genotype v je ...201121750744
mutational analysis of the zippering reaction during flavivirus membrane fusion.the current model of flavivirus membrane fusion is based on atomic structures of truncated forms of the viral fusion protein e in its dimeric prefusion and trimeric postfusion conformations. these structures lack the two transmembrane domains (tmds) of e as well as the so-called stem, believed to be involved in an intra- and intermolecular zippering reaction within the e trimer during the fusion process. in order to gain experimental evidence for the functional role of the stem in flavivirus mem ...201121697495
distribution and phylogenetic comparisons of a novel mosquito flavivirus sequence present in culex tarsalis mosquitoes from western canada with viruses isolated in california and a previous study, a new flavivirus genome sequence was identified in culex tarsalis mosquitoes obtained in alberta, canada and was shown to be genetically related to but distinct from members of the insect-specific flaviviruses. nonstructural protein 5-encoding sequences amplified from cx. tarsalis pools from western canada have shown a high similarity to genome sequences of novel flaviviruses isolated from mosquitoes in california and colorado. despite wide distribution of this virus, design ...201121734143
flavivirus rna cap methyltransferase: structure, function, and inhibition.many flaviviruses are significant human pathogens. the plus-strand rna genome of a flavivirus contains a 5' terminal cap 1 structure (m(7)gpppamg). the flavivirus encodes one methyltransferase (mtase), located at the n-terminal portion of the ns5 rna-dependent rna polymerase (rdrp). here we review recent advances in our understanding of flaviviral capping machinery and the implications for drug development. the ns5 mtase catalyzes both guanine n7 and ribose 2'-oh methylations during viral cap fo ...201021927615
Crystal structure of the Japanese encephalitis virus envelope protein.Japanese Encephalitis Virus (JEV) is the leading global cause of viral encephalitis. The JEV envelope protein (E) facilitates cellular attachment and membrane fusion and is the primary target of neutralizing antibodies. Herein, we have determined the 2.1Å resolution crystal structure of the JEV E ectodomain refolded from bacterial inclusion bodies. The E protein possesses the three domains characteristic of flavivirus envelopes and epitope mapping of neutralizing antibodies onto the structure re ...201122156523
misdiagnosis of early lyme disease as the summer flu.lyme disease is often identified by the hallmark erythema migrans rash, but not all early cases present with a rash. in other cases the rash may be unseen or unrecognized by a physician. in these situations, lyme disease is difficult to diagnose because it masquerades as a non-specific viral-like illness. the seasonal peak of lyme disease ranging from may through september overlaps with that of viral illnesses such as enteroviral infections, west nile virus, and in rare years such as 2009, early ...201122053255
evaluation of the human host range of bovine and porcine viruses that may contaminate bovine serum and porcine trypsin used in the manufacture of biological products.current u.s. requirements for testing cell substrates used in production of human biological products for contamination with bovine and porcine viruses are u.s. department of agriculture (usda) 9cfr tests for bovine serum or porcine trypsin. 9cfr requires testing of bovine serum for seven specific viruses in six families (immunofluorescence) and at least 2 additional families non-specifically (cytopathicity and hemadsorption). 9cfr testing of porcine trypsin is for porcine parvovirus. recent con ...201122000165
tick cell lines for study of crimean-congo hemorrhagic fever virus and other arboviruses.abstract continuous cell lines derived from many of the vectors of tick-borne arboviruses of medical and veterinary importance are now available. their role as tools in arbovirus research to date is reviewed and their potential application in studies of tick cell responses to virus infection is explored, by comparison with recent progress in understanding mosquito immunity to arbovirus infection. a preliminary study of propagation of the human pathogen crimean-congo hemorrhagic fever virus (cc ...201121955214
Tembusu virus in ducks, china.In China in 2010, a disease outbreak in egg-laying ducks was associated with a flavivirus. The virus was isolated and partially sequenced. The isolate exhibited 87%-91% identity with strains of Tembusu virus, a mosquito-borne flavivirus of the Ntaya virus group. These findings demonstrate emergence of Tembusu virus in ducks.201122000358
trim79α, an interferon-stimulated gene product, restricts tick-borne encephalitis virus replication by degrading the viral rna response to virus infection, type i interferons (ifns) induce several genes, most of whose functions are largely unknown. here, we show that the tripartite motif (trim) protein, trim79α, is an ifn-stimulated gene (isg) product that specifically targets tick-borne encephalitis virus (tbev), a flavivirus that causes encephalitides in humans. trim79α restricts tbev replication by mediating lysosome-dependent degradation of the flavivirus ns5 protein, an rna-dependent rna polymerase essential for ...201121925107
rapid molecular detection methods for arboviruses of livestock of importance to northern europe.arthropod-borne viruses (arboviruses) have been responsible for some of the most explosive epidemics of emerging infectious diseases over the past decade. their impact on both human and livestock populations has been dramatic. the early detection either through surveillance or diagnosis of virus will be a critical feature in responding and resolving the emergence of such epidemics in the future. although some of the most important emerging arboviruses are human pathogens, this paper aims to high ...201222219660
variability of powassan virus cultured in tissue explants and organism of hyalomma anatolicum ticks.the variability of powassan virus was studied during successive passages in hyalomma anatolicum ticks or prolonged reproduction in their tissue explants. it had been shown that in the course of tick passages and during reproduction in the explants, pathogenicity of the virus in respect to causing acute disease in mice after peripheral inoculation was decreased, while virus ability to cause death after intracerebral (i.c.) inoculation remained unchanged. in mice infected with the original strain ...20102864833
dose-dependent viremia and the differential immunoglobulin response of hamsters to powassan virus. 20134624393
[pathomorphology of experimental infection caused by powassan virus isolated in the primorskiĭ territory].pathomorphology of the infection caused by powassan virus strains isolated in the primorsky kray was studied in white mice. the central nervous system of the animals sacrificed in the time course of the infectious process was studied by light and luminescent microscopy. severe diffuse inflammatory-degenerative changes were found in the brain and spinal cord. immunofluorescence revealed cytoplasmic localization of the virus antigen in neurons, glial and connective tissue cells.1992206027
[electron microscopic study of the an-750 strain of powassan virus isolated in the soviet union].electron microscopic examinations of brains of white mice inoculated with the an 750 strain isolated for the first time from adult mosquitoes and with the prototype lb strain of powassan virus were carried out. the method of combination of light and electron microscopy used in the study permitted to compare ultrastructural changes in one cell with the results of light microscopy. sizes of virions and their localizations in the brain cells were determined. virus particles were found in large and ...1987211734
acute childhood encephalitis and meningoencephalitis: diagnosis and management.this paper seeks to discuss the differential diagnosis of childhood encephalitis and to review the course of investigation in a child presenting with encephalopathy, encephalitis and meningoencephalitis. the paper also reviews the current understanding of acute demyelinating encephalomyelitis (adem) and presents the crucial therapeutic alternatives in the management of childhood encephalitis, including adem and infectious diseases.199820401194
bioinformatics and expression analyses of the ixodes scapularis tick cystatin family.the cystatins are inhibitors of papain- and legumain-like cysteine proteinases, classified in merops subfamilies i25a-i25c. this study shows that 84 % (42/50) of tick cystatins are putatively extracellular in subfamily i25b and the rest are putatively intracellular in subfamily i25a. on the neighbor joining phylogeny guide tree, subfamily i25a members cluster together, while subfamily i25b cystatins segregate among prostriata or metastriata ticks. two ixodes scapularis cystatins, aay66864 and is ...201223053911
powassan virus encephalitis, minnesota, usa.powassan virus (powv) is a rare tick-borne agent of encephalitis in north america. historically, confirmed cases occurred mainly in the northeastern united states. since 2008, confirmed cases in minnesota and wisconsin have increased. we report a fatal case of powv encephalitis in minnesota. powv infection should be suspected in tick-exposed patients with viral encephalitis.201223017222
revisiting the clinal concept of evolution and dispersal for the tick-borne flaviviruses by using phylogenetic and biogeographic analyses.tick-borne flaviviruses (tbf) are widely dispersed across africa, europe, asia, oceania, and north america, and some present a significant threat to human health. seminal studies on tick-borne encephalitis viruses (tbev), based on partial envelope gene sequences, predicted a westward clinal pattern of evolution and dispersal across northern eurasia, terminating in the british isles. we tested this hypothesis using all available full-length open reading frame (orf) tbf sequences. phylogenetic ana ...201222674986
direct molecular detection and genotyping of borrelia burgdorferi from whole blood of patients with early lyme molecular tests in blood for early lyme disease can be insensitive due to low amount of circulating borrelia burgdorferi dna. to address this challenge, we have developed a sensitive strategy to both detect and genotype b. burgdorferi directly from whole blood collected during the initial patient visit. this strategy improved sensitivity by employing 1.25 ml of whole blood, a novel pre-enrichment of the entire specimen extract for borrelia dna prior to a multi-locus pcr and electrospray i ...201222590620
differential salivary gland transcript expression profile in ixodes scapularis nymphs upon feeding or flavivirus infection.ixodid ticks are vectors of human diseases such as lyme disease, babesiosis, anaplasmosis, and tick-borne encephalitis. these diseases cause significant morbidity and mortality worldwide and are transmitted to humans during tick feeding. the tick-host-pathogen interface is a complex environment where host responses are modulated by the molecules in tick saliva to enable the acquisition of a blood meal. disruption of host responses at the site of the tick bite may also provide an advantage for pa ...201222309855
sensitive multiplex pcr assay to differentiate lyme spirochetes and emerging pathogens anaplasma phagocytophilum and babesia microti.the infection with borrelia burgdorferi can result in acute to chronic lyme disease. in addition, coinfection with tick-borne pathogens, babesia species and anaplasma phagocytophilum has been increasing in endemic regions of the usa and europe. the currently used serological diagnostic tests are often difficult to interpret and, moreover, antibodies against the pathogens persist for a long time making it difficult to confirm the cure of the disease. in addition, these tests cannot be used for di ...201324359556
potential role of deer tick virus in powassan encephalitis cases in lyme disease-endemic areas of new york, u.s.a.powassan virus, a member of the tick-borne encephalitis group of flaviviruses, encompasses 2 lineages with separate enzootic cycles. the prototype lineage of powassan virus (powv) is principally maintained between ixodes cookei ticks and the groundhog (marmota momax) or striped skunk (mephitis mephitis), whereas the deer tick virus (dtv) lineage is believed to be maintained between ixodes scapularis ticks and the white-footed mouse (peromyscus leucopus). we report 14 cases of powassan encephalit ...201324274334
isolation of deer tick virus (powassan virus, lineage ii) from ixodes scapularis and detection of antibody in vertebrate hosts sampled in the hudson valley, new york state.deer tick virus, dtv, is a genetically and ecologically distinct lineage of powassan virus (powv) also known as lineage ii powv. human incidence of pow encephalitis has increased in the last 15 years potentially due to the emergence of dtv, particularly in the hudson valley of new york state. we initiated an extensive sampling campaign to determine whether powv was extant throughout the hudson valley in tick vectors and/or vertebrate hosts.201324016533
expression profiling of lymph node cells from deer mice infected with andes virus.deer mice (peromyscus maniculatus) are the principal reservoir hosts of sin nombre virus (snv), the cause of the great majority of hantavirus cardiopulmonary syndrome (hcps) cases in north america. snv, like all hantaviruses with their reservoirs, causes persistent infection without pathology in deer mice and appear to elicit a regulatory t cell response. deer mice are also susceptible to andes virus (andv), which causes the great majority of hcps cases in south america, but they clear infection ...201323570545
what is the risk for exposure to vector-borne pathogens in united states national parks?united states national parks attract > 275 million visitors annually and collectively present risk of exposure for staff and visitors to a wide range of arthropod vector species (most notably fleas, mosquitoes, and ticks) and their associated bacterial, protozoan, or viral pathogens. we assessed the current state of knowledge for risk of exposure to vector-borne pathogens in national parks through a review of relevant literature, including internal national park service documents and organismal ...201323540107
detection of human bacterial pathogens in ticks collected from louisiana black bears (ursus americanus luteolus).there are 4 major human-biting tick species in the northeastern united states, which include: amblyomma americanum, amblyomma maculatum, dermacentor variabilis, and ixodes scapularis. the black bear is a large mammal that has been shown to be parasitized by all the aforementioned ticks. we investigated the bacterial infections in ticks collected from louisiana black bears (ursus americanus subspecies luteolus). eighty-six ticks were collected from 17 black bears in louisiana from june 2010 to ma ...201323415850
vaccination against lyme disease: past, present, and future.lyme borreliosis is a zoonotic disease caused by borrelia burgdorferi sensu lato bacteria transmitted to humans and domestic animals by the bite of an ixodes spp. tick (deer tick). despite improvements in diagnostic tests and public awareness of lyme disease, the reported cases have increased over the past decade to approximately 30,000 per year. limitations and failed public acceptance of a human vaccine, comprised of the outer surface a (ospa) lipoprotein of b. burgdorferi, led to its demise, ...201323407755
borrelia burgdorferi promotes the establishment of babesia microti in the northeastern united states.babesia microti and borrelia burgdorferi, the respective causative agents of human babesiosis and lyme disease, are maintained in their enzootic cycles by the blacklegged tick (ixodes scapularis) and use the white-footed mouse (peromyscus leucopus) as primary reservoir host. the geographic range of both pathogens has expanded in the united states, but the spread of babesiosis has lagged behind that of lyme disease. several studies have estimated the basic reproduction number (r0) for b. microti ...201425545393
lyme borreliosis: a review of data on transmission time after tick attachment.lyme borreliosis is increasing rapidly in many parts of the world and is the most commonly occurring vector-borne disease in europe and the usa. the disease is transmitted by ticks of the genus ixodes. they require a blood meal at each stage of their life cycle and feed on a wide variety of wild and domestic animals as well as birds and reptiles. transmission to humans is incidental and can occur during visits to a vector habitat, when host mammals and their associated ticks migrate into the urb ...201425565881
borrelia burgdorferi (lyme disease). 201425452659
genetic variation in the mitochondrial 16s ribosomal rna gene of ixodes scapularis (acari: ixodidae).ixodes scapularis is a vector of several human pathogens in the united states, and there is geographical variation in the relative number of persons infected with these pathogens. geographically isolated populations of i. scapularis have established or are in the process of establishing in southern canada. knowledge of the genetic variation within and among these populations may provide insight into their geographical origins in the united states and the potential risk of exposure of canadians t ...201425430547
emerging and reemerging neurologic infections.the list of emerging and reemerging pathogens that cause neurologic disease is expanding. various factors, including population growth and a rise in international travel, have contributed to the spread of pathogens to previously nonendemic regions. recent advances in diagnostic methods have led to the identification of novel pathogens responsible for infections of the central nervous system. furthermore, new issues have arisen surrounding established infections, particularly in an increasingly i ...201425360203
virome analysis of amblyomma americanum, dermacentor variabilis, and ixodes scapularis ticks reveals novel highly divergent vertebrate and invertebrate viruses.a wide range of bacterial pathogens have been identified in ticks, yet the diversity of viruses in ticks is largely unexplored. in the united states, amblyomma americanum, dermacentor variabilis, and ixodes scapularis are among the principal tick species associated with pathogen transmission. we used high-throughput sequencing to characterize the viromes of these tick species and identified the presence of powassan virus and eight novel viruses. these included the most divergent nairovirus descr ...201425056893
lyme disease. 201425119621
population and demographic structure of ixodes scapularis say in the eastern united states.the most significant vector of tick-borne pathogens in the united states is ixodes scapularis say (the blacklegged tick). previous studies have identified significant genetic, behavioral and morphological differences between northern vs. southern populations of this tick. because tick-borne pathogens are dependent on their vectors for transmission, a baseline understanding of the vector population structure is crucial to determining the risks and epidemiology of pathogen transmission.201425025532
borrelia miyamotoi sensu lato seroreactivity and seroprevalence in the northeastern united states.borrelia miyamotoi sensu lato, a relapsing fever borrelia sp., is transmitted by the same ticks that transmit b. burgdorferi (the lyme disease pathogen) and occurs in all lyme disease-endemic areas of the united states. to determine the seroprevalence of igg against b. miyamotoi sensu lato in the northeastern united states and assess whether serum from b. miyamotoi sensu lato-infected persons is reactive to b. burgdorferi antigens, we tested archived serum samples from area residents during 1991 ...201424960072
chronic coinfections in patients diagnosed with chronic lyme disease: a systematic review.often, the controversial diagnosis of chronic lyme disease is given to patients with prolonged, medically unexplained physical symptoms. many such patients also are treated for chronic coinfections with babesia, anaplasma, or bartonella in the absence of typical presentations, objective clinical findings, or laboratory confirmation of active infection. we have undertaken a systematic review of the literature to evaluate several aspects of this practice.201424929022
clinical practice. lyme disease. 201424785207
the prevalence of borrelia miyamotoi infection, and co-infections with other borrelia spp. in ixodes scapularis ticks collected in canada.blacklegged ticks, ixodes scapularis are vectors of the tick-borne pathogens borrelia burgdorferi, anaplasma phagocytophilum and babesia microti. recently, the i. scapularis-borne bacterium borrelia miyamotoi has been linked to human illness in north america. the range of this tick is expanding in canada which may increase the potential for human exposure to these agents.201424731287
the prevalence of zoonotic tick-borne pathogens in ixodes scapularis collected in the hudson valley, new york state.ixodes scapularis, the blacklegged tick, is capable of transmitting the pathogens that cause lyme disease (borrelia burgdorferi), babesiosis (babesia microti), anaplasmosis (anaplasma phagocytophilum), and to a lesser extent powassan encephalitis (deer tick virus [dtv]). these pathogens represent significant public health problems, but little is known about the occurrence and co-infection prevalence of these pathogens in i. scapularis. here, we used standard pcr and pathogen-specific primers to ...201424689680
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