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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
outbreak of powassan encephalitis--maine and vermont, 1999-2001.powassan (pow) virus, a north american tickborne flavivirus related to the eastern hemisphere's tickborne encephalitis viruses, was first isolated from a patient with encephalitis in 1958. during 1958-1998, 27 human pow encephalitis cases were reported from canada and the northeastern united states. during september 1999-july 2001, four maine and vermont residents with encephalitis were found to be infected with pow virus. these persons were tested for other arbovirus infections found in the nor ...200111787585
nucleic acid sequence-based amplification assays for rapid detection of west nile and st. louis encephalitis viruses.the development and application of nucleic acid sequence-based amplification (nasba) assays for the detection of west nile (wn) and st. louis encephalitis (sle) viruses are reported. two unique detection formats were developed for the nasba assays: a postamplification detection step with a virus-specific internal capture probe and electrochemiluminescence (nasba-ecl assay) and a real-time assay with 6-carboxyfluorescein-labeled virus-specific molecular beacon probes (nasba-beacon assay). the sen ...200111724870
environmental health indicators of climate change for the united states: findings from the state environmental health indicator collaborative.to 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
genomic sequencing of deer tick virus and phylogeny of powassan-related viruses of north america.powassan (pow) virus is responsible for central nervous system infection in humans in north america and the eastern parts of russia. recently, a new flavivirus, deer tick (dt) virus, related to pow virus was isolated in the united states, but neither its pathogenic potential in human nor the taxonomic relationship with pow virus has been elucidated. in this study, we obtained the near-full-length genomic sequence of the dt virus and complete sequences of 3 genomic regions of 15 strains of pow-re ...200111716135
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
phylogeny of north american powassan virus.to determine whether powassan virus (pow) and deer tick virus (dtv) constitute distinct flaviviral populations transmitted by ixodid ticks in north america, we analysed diverse nucleotide sequences from 16 strains of these viruses. two distinct genetic lineages are evident, which may be defined by geographical and host associations. the nucleotide and amino acid sequences of lineage one (comprising new york and canadian pow isolates) are highly conserved across time and space, but those of linea ...200111413377
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
enzyme-linked immunosorbent assays using recombinant envelope protein expressed in cos-1 and drosophila s2 cells for detection of west nile virus immunoglobulin m in serum or cerebrospinal fluid.humans infected with west nile virus (wnv) develop immunoglobulin m (igm) antibodies soon after infection. the microtiter-based assays for wnv igm antibody detection used by most state public health and reference laboratories utilize wnv antigen isolated from infected vero cells or recombinant envelope protein produced in cos-1 cells. recombinant antigen produced in cos-1 cells was used to develop a wnv igm capture enzyme immunoassay (eia). a supplementary eia using wnv envelope protein expresse ...200415242936
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
use of recombinant e protein domain iii-based enzyme-linked immunosorbent assays for differentiation of tick-borne encephalitis serocomplex flaviviruses from mosquito-borne flaviviruses.the serological diagnosis of infection by flaviviruses is complicated by the presence of flavivirus cross-reactive antibodies that produce false-positive results for flavivirus infections, especially in regions where more than one virus is endemic. current diagnostic reagents for tick-borne flavivirus infection have been found to cross-react with yellow fever- or dengue virus-positive sera. this study utilized recombinant flavivirus e protein domain 3 (re-d3) as a diagnostic reagent to different ...200415364996
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
[genome sequence and antigen structure of the powassan virus: analysis of genetic elements of tick-transmitted flaviviruses]. 19957886964
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
noninfectious recombinant antigen for detection of st. louis encephalitis virus-specific antibodies in serum by enzyme-linked immunosorbent assay.proper surveillance of virus activity and a timely response to viral outbreaks depend upon the rapid diagnosis of viral infections. the immunoglobulin m (igm) antibody-capture enzyme-linked immunosorbent assay (mac-elisa) is a fast, sensitive test routinely used for the diagnosis of the medically important west nile and st. louis encephalitis flaviviruses. however, the suckling mouse brain-derived (smb) antigen used in this assay is tedious to prepare and has a risk of exposing personnel to live ...200415472331
an animal model for the tickborne flavivirus--omsk hemorrhagic fever virus.the tickborne encephalitis (tbe) serocomplex of flaviviruses consists primarily of viruses that cause neurologic disease; these viruses include omsk hemorrhagic fever virus (ohfv), a virus that is genetically related to other tbe serocomplex viruses but that circulates in an ecologically distinct niche and causes markedly different human disease. the objective of this study was to examine a potential small-animal model for ohfv and to compare the pathology of infection with that of the neurotrop ...200415593010
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 2009.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 rash of west nile virus infection. 200515911857
comparative analysis of immunoglobulin m (igm) capture enzyme-linked immunosorbent assay using virus-like particles or virus-infected mouse brain antigens to detect igm antibody in sera from patients with evident flaviviral infections.the use of immunoglobulin m (igm) antibody-capture enzyme-linked immunosorbent assay (mac-elisa) serves as a valuable tool for the diagnosis of acute flaviviral infections, since igm antibody titers are detectable early, peak at about 2 weeks postinfection, and subsequently decline to lower levels over the next few months. traditionally, virus-infected tissue culture or suckling mouse brain (smb) has been the source of viral antigens used in the assay. in an effort to provide a reliable source o ...200516000440
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
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
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 colorado.in 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
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
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 polymerase.in 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
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
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
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
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
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
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
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
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
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
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
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
laboratory identification of arthropod ectoparasites.the collection, handling, identification, and reporting of ectoparasitic arthropods in clinical and reference diagnostic laboratories are discussed in this review. included are data on ticks, mites, lice, fleas, myiasis-causing flies, and bed bugs. the public health importance of these organisms is briefly discussed. the focus is on the morphological identification and proper handling and reporting of cases involving arthropod ectoparasites, particularly those encountered in the united states. o ...201424396136
emerging horizons for tick-borne pathogens: from the 'one pathogen-one disease' vision to the pathobiome paradigm.ticks, as vectors of several notorious zoonotic pathogens, represent an important and increasing threat for human and animal health in europe. recent applications of new technology revealed the complexity of the tick microbiome, which may affect its vectorial capacity. appreciation of these complex systems is expanding our understanding of tick-borne pathogens, leading us to evolve a more integrated view that embraces the 'pathobiome'; the pathogenic agent integrated within its abiotic and bioti ...201526610021
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
coinfection by ixodes tick-borne pathogens: ecological, epidemiological, and clinical consequences.ixodes ticks maintain a large and diverse array of human pathogens in the enzootic cycle, including borrelia burgdorferi and babesia microti. despite the poor ecological fitness of b. microti, babesiosis has recently emerged in areas endemic for lyme disease. studies in ticks, reservoir hosts, and humans indicate that coinfection with b. burgdorferi and b. microti is common, promotes transmission and emergence of b. microti in the enzootic cycle, and causes greater disease severity and duration ...201526613664
ticknet-a collaborative public health approach to tickborne disease surveillance and research.ticknet, a public health network, was created in 2007 to foster greater collaboration between state health departments, academic centers, and the centers for disease control and prevention on surveillance and prevention of tickborne diseases. research activities are conducted through the emerging infections program and include laboratory surveys, high-quality prevention trials, and pathogen discovery.201526291549
experimental transmission of karshi (mammalian tick-borne flavivirus group) virus by ornithodoros ticks >2,900 days after initial virus exposure supports the role of soft ticks as a long-term maintenance mechanism for certain flaviviruses.members of the mammalian tick-borne flavivirus group, including tick-borne encephalitis virus, are responsible for at least 10,000 clinical cases of tick-borne encephalitis each year. to attempt to explain the long-term maintenance of members of this group, we followed ornithodoros parkeri, o. sonrai, and o. tartakovskyi for >2,900 days after they had been exposed to karshi virus, a member of the mammalian tick-borne flavivirus group.201526285211
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
whole genome capture of vector-borne pathogens from mixed dna samples: a case study of borrelia burgdorferi.rapid and accurate retrieval of whole genome sequences of human pathogens from disease vectors or animal reservoirs will enable fine-resolution studies of pathogen epidemiological and evolutionary dynamics. however, next generation sequencing technologies have not yet been fully harnessed for the study of vector-borne and zoonotic pathogens, due to the difficulty of obtaining high-quality pathogen sequence data directly from field specimens with a high ratio of host to pathogen dna.201526048573
babesiosis.babesiosis is caused by intraerythrocytic protozoan parasites that are transmitted by ticks, or less commonly through blood transfusion or transplacentally. human babesiosis was first recognized in a splenectomized patient in europe but most cases have been reported from the northeastern and upper midwestern united states in people with an intact spleen and no history of immune impairment. cases are reported in asia, africa, australia, europe, and south america. babesiosis shares many clinical f ...201525999229
human granulocytic anaplasmosis.human granulocytic anaplasmosis, a deer tick-transmitted rickettsial infection caused by anaplasma phagocytophilum, is a common cause of undifferentiated fever in the northeast and upper midwest united states. patients are often initially diagnosed with a mild viral infection, and illness readily resolves in most cases. however, as many as 3% develop life-threatening complications and nearly 1% die from the infection. although coinfections with borrelia burgdorferi and babesia microti occur, the ...201525999228
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
accelerated phenology of blacklegged ticks under climate warming.the phenology of tick emergence has important implications for the transmission of tick-borne pathogens. a long lag between the emergence of tick nymphs in spring and larvae in summer should increase transmission of persistent pathogens by allowing infected nymphs to inoculate the population of naive hosts that can subsequently transmit the pathogen to larvae to complete the transmission cycle. in contrast, greater synchrony between nymphs and larvae should facilitate transmission of pathogens t ...201525688016
identification of 24h ixodes scapularis immunogenic tick saliva proteins.ixodes scapularis is arguably the most medically important tick species in the united states. this tick transmits 5 of the 14 human tick-borne disease (tbd) agents in the usa: borrelia burgdorferi, anaplasma phagocytophilum, b. miyamotoi, babesia microti, and powassan virus disease. except for the powassan virus disease, i. scapularis-vectored tbd agents require more than 24h post attachment to be transmitted. this study describes identification of 24h immunogenic i. scapularis tick saliva prote ...201525825233
loop analysis for pathogens: niche partitioning in the transmission graph for pathogens of the north american tick ixodes scapularis.in 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
bunyaviruses are common in male and female ixodes scapularis ticks in central pennsylvania.the blacklegged tick ixodes scapularis is widely distributed in the united states and transmits multiple pathogens to humans, wildlife and domestic animals. recently, several novel viruses in the family bunyaviridae (south bay virus (sbv) and blacklegged tick phlebovirus (btpv)) were identified infecting female i. scapularis ticks collected in new york state. we used metagenomic sequencing to investigate the distribution of viruses infecting male and female i. scapularis ticks collected in centr ...201627602290
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
prevalence of the lyme disease spirochete, borrelia burgdorferi, in blacklegged ticks, ixodes scapularis at hamilton-wentworth, ontario.lyme disease has emerged as a major health concern in canada, where the etiological agent, borrelia burgdorferi sensu lato (s.l.), a spirochetal bacterium, is typically spread by the bite of certain ticks. this study explores the presence of b. burgdorferi s.l. in blacklegged ticks, ixodes scapularis, collected at dundas, ontario (a locality within the region of hamilton-wentworth). using passive surveillance, veterinarians and pet groomers were asked to collect blacklegged ticks from dogs and c ...201627226771
ixodes scapularis tick saliva proteins sequentially secreted every 24 h during blood feeding.ixodes scapularis is the most medically important tick species and transmits five of the 14 reportable human tick borne disease (tbd) agents in the usa. this study describes lc-ms/ms identification of 582 tick- and 83 rabbit proteins in saliva of i. scapularis ticks that fed for 24, 48, 72, 96, and 120 h, as well as engorged but not detached (bd), and spontaneously detached (sd). the 582 tick proteins include proteases (5.7%), protease inhibitors (7.4%), unknown function proteins (22%), immunity ...201626751078
lyme disease risk in southern california: abiotic and environmental drivers of ixodes pacificus (acari: ixodidae) density and infection prevalence with borrelia burgdorferi.tick-borne diseases, particularly lyme disease, are emerging across the northern hemisphere. in order to manage emerging diseases and predict where emergence will likely occur, it is necessary to understand the factors influencing the distribution, abundance and infection prevalence of vector species. in north america, lyme disease is the most common vector-borne disease and is transmitted by blacklegged ticks. this study aimed to explore the abiotic and environmental drivers of density and infe ...201728057067
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
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
alkhurma hemorrhagic fever virus in ornithodoros savignyi ticks.evidence for the tickborne nature of alkhurma hemorrhagic fever virus (ahfv) is indirect because ahfv has not been detected in arthropods. one ornithodoros savignyi tick from saudi arabia contained ahfv rna. this is the first direct evidence that ahfv is a tickborne flavivirus and confirms the association between human ahfv cases and tickbite history.200717370534
serological studies of west nile virus in a liver transplant population.background: solid organ transplant populations are at increased risk for serious clinical manifestations of west nile virus (wnv) infection. objective: to monitor liver transplant recipients during the 2003 wnv season in manitoba and to identify incidence, clinical presentation and serology. methods: serial blood specimens were obtained from adult patients followed at the liver transplant outpatient clinic between may 2003 and october 2003. studies for wnv infection included immunoglobulin (ig) ...200418159505
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