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dengue epidemic in children in delhi region 2006--similarities to the karachi epidemic of 2006. 200818998322
structural and functional studies of the promoter element for dengue virus rna replication.the 5' untranslated region (5'utr) of the dengue virus (denv) genome contains two defined elements essential for viral replication. at the 5' end, a large stem-loop (sla) structure functions as the promoter for viral polymerase activity. next to the sla, there is a short stem-loop that contains a cyclization sequence known as the 5' upstream aug region (5'uar). here, we analyzed the secondary structure of the sla in solution and the structural requirements of this element for viral replication. ...200919004935
functional importance of dengue virus maturation: infectious properties of immature virions.prior to the release of flavivirus particles from infected cells, the viral surface protein prm is cleaved to m by the cellular enzyme furin. for dengue virus (denv), this maturation process appears to be very inefficient since a high proportion of progeny virions contain uncleaved prm. furthermore, it has been reported that prm-containing denv particles are infectious. these observations contradict the general assumption that prm processing is required to render virus particles infectious. ther ...200819008392
a glycosylated peptide in the west nile virus envelope protein is immunogenic during equine infection.using a monoclonal antibody directed to domain i of the west nile virus (wnv) envelope (e) protein, we identified a continuous (linear) epitope that was immunogenic during wnv infection of horses. using synthetic peptides, this epitope was mapped to a 19 aa sequence (wn19: e147-165) encompassing the wnv ny99 e protein glycosylation site at position 154. the inability of wnv-positive horse and mouse sera to bind the synthetic peptides indicated that glycosylation was required for recognition of p ...200819008394
insights into rna unwinding and atp hydrolysis by the flavivirus ns3 protein.together with the ns5 polymerase, the ns3 helicase has a pivotal function in flavivirus rna replication and constitutes an important drug target. we captured the dengue virus ns3 helicase at several stages along the catalytic pathway including bound to single-stranded (ss) rna, to an atp analogue, to a transition-state analogue and to atp hydrolysis products. rna recognition appears largely sequence independent in a way remarkably similar to eukaryotic dead box proteins vasa and eif4aiii. on ssr ...200819008861
scientific consultation on cell mediated immunity (cmi) in dengue and dengue vaccine development.dengue is a re-emerging arboviral disease of great public health importance. limited understanding of protective immune responses against dengue has hampered advancement of dengue vaccine candidates. demonstrating an immunological correlate of protection has been limited to associating quantitative neutralizing antibody titers with clinical outcomes following infection. there have been a number of studies investigating the role of cell mediated immunity (cmi) in natural infections and these have ...200919022321
antiviral activity of benzimidazole derivatives. i. antiviral activity of 1-substituted-2-[(benzotriazol-1/2-yl)methyl]benzimidazoles.forty-three 2-[(benzotriazol-1/2-yl)methyl]benzimidazoles, bearing either linear (dialkylamino)alkyl- or bulkier (quinolizidin-1-yl)alkyl moieties at position 1, were evaluated in cell-based assays for cytotoxicity and antiviral activity against viruses representative of two of the three genera of the flaviviridae family, i.e. flaviviruses (yellow fever virus (yfv)) and pestiviruses (bovine viral diarrhoea virus (bvdv)), as hepaciviruses can hardly be used in routine cell-based assays. compounds ...200819035566
serological survey of domestic animals for tick-borne encephalitis and bhanja viruses in northeastern hungary.blood sera collected from 400 domestic animals (260 cattle, 100 merino sheep, and 40 hutzul horses) in northeastern hungary in 2005 were examined for antibodies against two tick-borne viruses, tick-borne encephalitis flavivirus (tbev) and bhanja bunyavirus (bhav). using elisa as screening test and plaque-reduction neutralization as confirmatory test, seropositivity to tbev was found to be 26.5% in cattle, 7.0% in sheep, and 0.0% in horses. among cattle, the animals up to 3 years old had signific ...200919036537
dengue-yellow fever sera cross-reactivity; challenges for diagnosis.the flavivirus genera share epitopes inducing cross-reactive antibodies leading to great difficulty in differentially diagnosing flaviviral infections. this work was aimed at evaluating the complexity of dengue and yellow fever serological differential diagnosis.200819039426
does variation in culex (diptera: culicidae) vector competence enable outbreaks of west nile virus in california?since the invasion of california by west nile virus (family flaviviridae, genus flavivirus, wnv) in 2003, we have annually monitored vector competence for the ny99 strain in culex tarsalis coquillett, culex pipiens quinquefasciatus say, culex p. pipiens l., and culex stigmatosoma dyar populations from four areas: deserts of coachella valley, densely urbanized maritime los angeles, southern san joaquin valley in kern county, and southern sacramento valley near davis in sacramento county. overall, ...200819058638
culex flavivirus isolates from mosquitoes in guatemala.a new strain of culex flavivirus (family flaviviridae, genus flavivirus, cxfv), an insect virus first described in japan, was isolated from adult culex quinquefasciatus say (diptera: culicidae) collected in 2006 from izabal department on the caribbean coast of guatemala. mosquito pools were assayed for flavivirus rna by using flavivirus group-specific primers that amplified a 720-bp region of the nonstructural (ns) 5 gene by standard reverse transcriptase-polymerase chain reaction. from 210 pool ...200819058647
structure of west nile virus ns3 protease: ligand stabilization of the catalytic conformation.over the last decade, west nile virus has spread rapidly via mosquito transmission from infected migratory birds to humans. one potential therapeutic approach to treating infection is to inhibit the virally encoded serine protease that is essential for viral replication. here we report the crystal structure of the viral ns3 protease tethered to its essential ns2b cofactor and bound to a potent substrate-based tripeptide inhibitor, 2-naphthoyl-lys-lys-arg-h (k(i)=41 nm), capped at the n-terminus ...200919059417
a single-amino acid substitution in west nile virus 2k peptide between ns4a and ns4b confers resistance to lycorine, a flavivirus inhibitor.lycorine potently inhibits flaviviruses in cell culture. at 1.2-microm concentration, lycorine reduced viral titers of west nile (wnv), dengue, and yellow fever viruses by 10(2)- to 10(4)-fold. however, the compound did not inhibit an alphavirus (western equine encephalitis virus) or a rhabdovirus (vesicular stomatitis virus), indicating a selective antiviral spectrum. the compound exerts its antiviral activity mainly through suppression of viral rna replication. a val-->met substitution at the ...200919062063
waste not, want not: a viral rna degradation product modulates west nile virus pathogenesis.in this issue of cell host & microbe, pijlman et al. define the structure and mechanism of generation of a small viral noncoding rna present in flavivirus-infected cells that has a marked impact on the fate of infected cells and virulence in vivo.200819064251
a highly structured, nuclease-resistant, noncoding rna produced by flaviviruses is required for pathogenicity.viral noncoding rnas have been shown to play an important role in virus-host interplay to facilitate virus replication. we report that members of the genus flavivirus, a large group of medically important encephalitic rna viruses, produce a unique and highly structured noncoding rna of 0.3-0.5 kb derived from the 3' untranslated region of the viral genome. using west nile virus as a model, we show that this subgenomic rna is a product of incomplete degradation of viral genomic rna by cellular ri ...200819064258
japanese encephalitis and vaccines: past and future prospects.the japanese encephalitis virus is the main cause of encephalitis in asia. the vectors are mosquitoes. every year 30,000 to 50,000 cases and 10,000 deaths from japanese encephalitis are reported, and estimates go up to 100,000 cases. no effective antiviral therapy exists to treat this flavivirus infection. for prophylaxis vaccines are available. in asia numerous vaccines are used regionally. the production of the only vaccine that was internationally licensed, je-vax, was ceased in 2005. therefo ...200819066766
ecology and geographical expansion of japanese encephalitis virus.japanese encephalitis virus (jev) (flavivirus: flaviviridae) is a leading cause of encephalitis in eastern and southern asia. the virus is maintained in a zoonotic cycle between ardeid wading birds and/or pigs and culex mosquitoes. the primary mosquito vector of jev is culex tritaeniorhynchus, although species such as cx. gelidus, cx. fuscocephala, and cx. annulirostris are important secondary or regional vectors. control of jev is achieved through human and/or swine vaccination, changes in anim ...200919067628
the hepatitis c virus ns4b protein can trans-complement viral rna replication and modulates production of infectious virus.studies of the hepatitis c virus (hcv) life cycle have been aided by development of in vitro systems that enable replication of viral rna and production of infectious virus. however, the functions of the individual proteins, especially those engaged in rna replication, remain poorly understood. it is considered that ns4b, one of the replicase components, creates sites for genome synthesis, which appear as punctate foci at the endoplasmic reticulum (er) membrane. in this study, a panel of mutatio ...200919073716
construction and characterization of a single-cycle chimeric flavivirus vaccine candidate that protects mice against lethal challenge with dengue virus type 2.we have previously described a novel flavivirus vaccine technology based on a single-cycle, capsid (c) gene-deleted flavivirus called replivax. replivax can be propagated in cells that express high levels of c but undergoes only a single cycle of infection in vaccinated hosts. here we report that we have adapted our replivax technology to produce a dengue vaccine by replacing the prm/e genes of replivax wn (a west nile virus [wnv] replivax) with the same genes of dengue virus type 2 (denv2). our ...200919073745
third-generation flavivirus vaccines based on single-cycle, encapsidation-defective viruses.flaviviruses are arthropod-borne pathogens that cause significant disease on all continents of the world except antarctica. flavivirus diseases are particularly important in tropical regions where arthropod vectors are abundant. live-attenuated virus vaccines (lavs) and inactivated virus vaccines (invs) exist for some of these diseases. lavs are economical to produce and potent, but are not suitable for use in the immunocompromised. invs are safer, but are more expensive to produce and less pote ...200819081489
severe tick-borne encephalitis in a patient previously infected by west nile virus.we describe severe tick-borne encephalitis (tbe) in a patient who had previously experienced west nile fever, another flavivirus infection endemic in hungary. previous west nile virus infection does not develop immunity either against tbe virus infection or the disease, and it does not mitigate its clinical course. the possibility of antibody-dependent enhancement is considered.200819086342
a kunjin replicon vector encoding granulocyte macrophage colony-stimulating factor for intra-tumoral gene therapy.we have recently developed a non-cytopathic rna replicon-based viral vector system based on the flavivirus kunjin. here, we illustrate the utility of the kunjin replicon system for gene therapy. intra-tumoral injections of kunjin replicon virus-like particles encoding granulocyte colony-stimulating factor were able to cure >50% of established subcutaneous ct26 colon carcinoma and b16-ova melanomas. regression of ct26 tumours correlated with the induction of anti-cancer cd8 t cells, and treatment ...200919092857
characterization of dengue complex-reactive epitopes on dengue 3 virus envelope protein domain iii.the disease dengue (den) is caused by four genetically and serologically related viruses termed denv-1, -2, -3, and -4. the denv envelope (e) protein ectodomain can be divided into three structural domains designated ed1, ed2, and ed3. the ed3 contains the denv type-specific and denv complex-reactive (epitopes shared by denv 1-4) antigenic sites. in this study the epitopes recognized by four denv complex-reactive monoclonal antibodies (mabs) with neutralizing activity were mapped on the denv-3 e ...200919101005
analysis of flavivirus ns5 methyltransferase cap binding.the flavivirus 2'-o-nucleoside n-terminal rna methyltransferase (mtase) enzyme is responsible for methylating the viral rna cap structure. to increase our understanding of the mechanism of viral rna cap binding we performed a detailed structural and biochemical characterization of the guanosine cap-binding pocket of the dengue (den) and yellow fever (yf) virus mtase enzymes. we solved an improved 2.1 a resolution crystal structure of den2 mtase, new 1.5 a resolution crystal structures of the yf ...200919101564
production of a monoclonal antibody against non-structural protein 3 of dengue-2 virus by intrasplenic injection.dengue fever and dengue hemorrhagic fever/dengue shock syndrome are highly infectious diseases caused by dengue virus (dv). dv non-structural protein 3 (ns3) is known to possess atpase, helicase, and protease activity that is a constitutive part of the replication complex of dv. in this study, we discuss the cloning, expression, and purification of the dv-2 ns3 protein to immunize mice by intrasplenic injection and then to generate a monoclonal antibody (mab). one mab, named 4f5, was obtained an ...200819108619
an unusual complication of dengue infection.we present an unusual complication of dengue infection resulting in postviral phrenic neuropathy and diaphragmatic paralysis in a 34-year-old man. there is a paucity of literature on this condition, with postviral neuropathies previously reported to be associated commonly with herpes zoster, poliovirus, and rarely, west nile virus and human immunodeficiency virus infections. to our knowledge, this is the first reported case of flavivirus causing isolated postviral phrenic neuropathy and diaphrag ...200819122929
mosquito-based survey for the detection of flaviviruses and filarial nematodes in aedes albopictus and other anthropophilic mosquitoes collected in northern italy.in order to optimize resources, an assay allowing the detection of several etiological agents would be useful. this paper describes a polymerase chain reaction (pcr)-based assay for the parallel detection of different pathogens in mosquitoes (diptera: culicidae). the assay combines the analysis of both rna and dna, hence allowing the detection of both flaviviruses (flaviviridae: flavivirus) and filarial nematodes (spirurida: onchocercidae). the sensitivity of diagnostic assay for both flavivirus ...200819123300
detection of rna from a novel west nile-like virus and high prevalence of an insect-specific flavivirus in mosquitoes in the yucatan peninsula of mexico.as part of our ongoing surveillance efforts for west nile virus (wnv) in the yucatan peninsula of mexico, 96,687 mosquitoes collected from january through december 2007 were assayed by virus isolation in mammalian cells. three mosquito pools caused cytopathic effect. two isolates were orthobunyaviruses (cache valley virus and kairi virus) and the identity of the third infectious agent was not determined. a subset of mosquitoes was also tested by reverse transcription-polymerase chain reaction (r ...200919141845
survival of mice immunized with monoclonal antibodies against glycoprotein e of japanese encephalitis virus before or after infection with japanese encephalitis, west nile, and dengue viruses.in the present study, the effect of monoclonal antibodies (mabs) against glycoprotein e (ge) of japanese encephalitis virus (jev) strain 733913 administered 1 day before or 2 days after intracerebral (i.c.) challenge with west nile virus (wnv) strain 68856 or dengue virus (denv-2) strain p23085, was studied in mice. furthermore, two jev strains belonging to group ii (strains 641686 and 691004) that have lost reactivity against virus-specific mabs were also used in passive immunization experiment ...200819143477
west nile virus in the americas.since the first detection of west nile virus in the western hemisphere in 1999, the virus has spread rapidly across the north american continent and as far south as argentina. an unprecedented pattern of large annual epidemics of human neuroinvasive disease continues in north america, resulting in considerable public health impact. the high infection incidence in humans has resulted in non-mosquito transmission modes, such as through transfused blood and transplanted organs. west nile virus incu ...200819145778
synthesis of the first example of a nucleoside analogue bearing a 5'-deoxy-beta-d-allo-septanose as a seven-membered ring sugar moiety.the first example of a nucleoside analogue bearing a 5'-deoxy-beta-d-allo-septanose as a seven-membered ring sugar moiety, namely 9-(5-deoxy-beta-d-allo-septanosyl)-adenine, is reported. this compound was synthesized in 14 steps from the commercially available d-glycero-d-gulo-1,4-lactone. when evaluated in cell culture experiments against a broad range of viruses, it did not exhibit any significant antiviral effect or cytotoxicity.200919147123
development of real time pcr for detection and quantitation of dengue viruses.dengue virus (denv), a mosquito borne flavivirus is an important pathogen causing more than 50 million infections every year around the world. dengue diagnosis depends on serology, which is not useful in the early phase of the disease and virus isolation, which is laborious and time consuming. there is need for a rapid, sensitive and high throughput method for detection of denv in the early stages of the disease. several real-time pcr assays have been described for dengue viruses, but there is s ...200919166574
analysis of the nucleoside triphosphatase, rna triphosphatase, and unwinding activities of the helicase domain of dengue virus ns3 protein.the helicase domain of dengue virus ns3 protein (denv ns3h) contains rna-stimulated nucleoside triphosphatase (ntpase), atpase/helicase, and rna 5'-triphosphatase (rtpase) activities that are essential for viral rna replication and capping. here, we show that denv ns3h unwinds 3'-tailed duplex with an rna but not a dna loading strand, and the helicase activity is poorly processive. the substrate of the divalent cation-dependent rtpase activity is not restricted to viral rna 5'-terminus, a protru ...200919166847
spatial spreading of west nile virus described by traveling waves.in this work, we propose a spatial model to analyze the west nile virus propagation across the usa, from east to west. west nile virus is an arthropod-borne flavivirus that appeared for the first time in new york city in the summer of 1999 and then spread prolifically among birds. mammals, such as humans and horses, do not develop sufficiently high bloodstream titers to play a significant role in the transmission, which is the reason to consider the mosquito-bird cycle. the model aims to study t ...200919167405
rna interference inhibits yellow fever virus replication in vitro and in vivo.rna interference (rnai) is a process that is induced by double stranded rna and involves the degradation of specific sequences of mrna in the cytoplasm of the eukaryotic cells. it has been used as an antiviral tool against many viruses, including flaviviruses. the genus flavivirus contains the most important arboviruses in the world, i.e., dengue (denv) and yellow fever (yfv). in our study, we investigated the in vitro and in vivo effect of rnai against yfv. using stable cell lines that expresse ...200919169857
in vitro activity and preclinical profile of tmc435350, a potent hepatitis c virus protease inhibitor.the hepatitis c virus (hcv) ns3/4a serine protease has been explored as a target for the inhibition of viral replication in preclinical models and in hcv-infected patients. tmc435350 is a highly specific and potent inhibitor of ns3/4a protease selected from a series of novel macrocyclic inhibitors. in biochemical assays using ns3/4a proteases of genotypes 1a and 1b, inhibition constants of 0.5 and 0.4 nm, respectively, were determined. tmc435350 inhibited hcv replication in a cellular assay (sub ...200919171797
diagnosis of turkey meningoencephalitis virus infection in field cases by rt-pcr compared to virus isolation in embryonated eggs and suckling mice.turkey meningoencephalitis (tme) is a paralytic epornitic disease of turkeys caused by turkey meningoencephalitis virus (tmev), an arthopod-borne flavivirus belonging to the ntaya serogroup vi. a tmev specific rt-pcr was compared with classical techniques for tmev diagnosis, which include virus isolation in 8-day-old chicken embryonated eggs and suckling mice, on 17 tme flocks with neurological signs that occurred during the fall of 1997. in 11/17 flocks both the rt-pcr and the virus isolation m ...200019184786
a heterocyclic molecule with significant activity against dengue virus.there are no specific approved drugs or vaccines for the treatment or prevention of infectious dengue virus and there are very few compounds known that inhibit the replication of this virus. this letter describes the concise synthesis of two uracil-based multifunctional compounds. one of these compounds (1) has strong activity against dengue virus. it also exhibits low activity against a few other rna viruses, but is highly active against yellow fever virus, a related flavivirus. it is likely th ...200919185487
identification of a virus-specific and conserved b-cell epitope on ns1 protein of japanese encephalitis virus.ns1 protein of japanese encephalitis virus (jev) is an important non-structural protein, which is able to induce protective immune response in target animals and can be used as specific serological diagnosis tool, but the epitopes on ns1 of jev have not been identified. for epitope mapping, in this study, a series of 51 partially overlapping fragments covering entire ns1 protein were expressed with a gst-tag and then screened by a monoclonal antibody (mab). through enzyme-linked immunosorbent as ...200919185592
the flaviviral methyltransferase is a substrate of casein kinase 1.serine/threonine phosphorylation of the nonstructural protein 5 (ns5) is a conserved feature of flaviviruses, but the identity and function(s) of the responsible kinase(s) remain unknown. serine 56 in the methyltransferase domain of ns5 can be phosphorylated intracellularly, is conserved in all flaviviruses, and is a critical residue in the catalytic mechanism. a negative charge at this residue inactivates the 2'-0 methyltransferase activity necessary to form a 5' cap structure of the viral rna. ...200919185594
modeling gene sequence changes over time in type 3 dengue viruses from ecuador.dengue virus (denv) is a member of the genus flavivirus of the family flaviviridae. denv-3 re-emerged in central america in 1994, and continues to expand into the south american region. little is known about the evolutionary rates, viral spread and population dynamics of this genotype in the latin american region. in order to gain insight into these matters, we used a bayesian markov chain monte carlo (mcmc) approach, to analyze envelope (e) gene sequences of the denv-3 genotype iii of strains i ...200919185597
identification of the nonstructural protein 4b of hepatitis c virus as a factor that inhibits the antiviral activity of interferon-alpha.interferon-alpha (ifn-alpha) is the most commonly used therapeutics for the treatment of chronic viral infection. however, many viruses are resistant to ifn-alpha treatment to some degrees through encoding inhibitors of the ifn-alpha producing or signaling pathway. multiple hcv viral proteins have been reported to be involved in ifn-alpha resistance. to develop a method to screen for factors that inhibit the antiviral activity of ifn-alpha, a mini-library of hcv genome was transduced into the hu ...200919185598
evaluation of interferences between dengue vaccine serotypes in a monkey model.interferences between different antigens in the same vaccine formulation have been reported for some vaccines (e.g., polio vaccines, live attenuated dengue vaccine candidates). we examined interferences between the four serotypes of chimerivax dengue vaccines (cyds) in a monkey model when present within a tetravalent formulation in equal concentrations (tv-5555). immunoassays of vaccinated non-human primates showed that serotype 4 (den-4), and to a lesser extent, den-1 were dominant in terms of ...200919190230
japanese encephalitis vaccine (inactivated, adsorbed) [ixiaro].the japanese encephalitis vaccine ic-51 (ixiaro) is an inactivated virus (strain sa(14)-14-2) that is manufactured in cultured vero cells and is currently being developed for preventive vaccination against the japanese encephalitis virus. black triangle administration of ixiaro as a two-dose treatment in healthy adults provided high levels of seroprotection against japanese encephalitis virus. immune responses at 56 days post-vaccination, including seroconversion rates and geometric mean titres, ...200919192940
characterization of culex flavivirus (flaviviridae) strains isolated from mosquitoes in the united states and trinidad.recent reports indicate that flaviviruses similar to the cell fusing agent virus (cfav) naturally infect a wide variety of mosquito species. these newly recognized insect-specific viruses comprise a distinct cfav complex within the genus flavivirus. here, we describe the isolation and characterization of nine strains of culex flavivirus (cx fv), a member of the cfav complex, from mosquitoes collected in the united states (east texas) and trinidad. phylogenetic analyses of the envelope protein ge ...200919193389
gbv-c viremia is associated with reduced cd4 expansion in hiv-infected people receiving haart and interleukin-2 therapy.interleukin-2 (il-2) is a cytokine with multiple effects on lymphocytes including induction of cd4 t-cell proliferation. il-2 administration has been shown to increase cd4 cell counts in hiv-infected people receiving antiretroviral therapy. gb virus c (gbv-c) is an apparently nonpathogenic flavivirus that replicates in cd4 t cells and inhibits hiv replication in vitro by mechanisms including downregulation of hiv entry coreceptors (ccr5 and cxcr4) and induction of chemokines (rantes, mip-1alpha, ...200919194270
ticks associated with macquarie island penguins carry arboviruses from four genera.macquarie island, a small subantarctic island, is home to rockhopper, royal and king penguins, which are often infested with the globally distributed seabird tick, ixodes uriae. a flavivirus, an orbivirus, a phlebovirus, and a nairovirus were isolated from these ticks and partial sequences obtained. the flavivirus was nearly identical to gadgets gully virus, isolated some 30 year previously, illustrating the remarkable genetic stability of this virus. the nearest relative to the orbivirus (for w ...200919194498
a conserved predicted pseudoknot in the ns2a-encoding sequence of west nile and japanese encephalitis flaviviruses suggests ns1' may derive from ribosomal frameshifting.japanese encephalitis, west nile, usutu and murray valley encephalitis viruses form a tight subgroup within the larger flavivirus genus. these viruses utilize a single-polyprotein expression strategy, resulting in ~10 mature proteins. plotting the conservation at synonymous sites along the polyprotein coding sequence reveals strong conservation peaks at the very 5' end of the coding sequence, and also at the 5' end of the sequence encoding the ns2a protein. such peaks are generally indicative of ...200919196463
flavivirus ns5 associates with host-cell proteins zonula occludens-1 (zo-1) and regulating synaptic membrane exocytosis-2 (rims2) via an internal pdz binding mechanism.dengue virus (denv) and tick-borne encephalitis virus (tbev) are flaviviruses, which can cause lethal hemorrhagic fever and encephalitis, respectively. here, we demonstrate that the tbev-ns5 and denv-ns5 proteins use an internal binding mechanism to target human pdz proteins. tbev-ns5 has high affinity to regulating synaptic membrane exocytosis-2 (rims2) and scribble, whereas denv-ns5 binds primarily to the tight junction protein zonula occludens-1 (zo-1). targeting of tbev-ns5 to the plasma mem ...200919199833
toll-like receptor 7 mitigates lethal west nile encephalitis via interleukin 23-dependent immune cell infiltration and homing.west nile virus (wnv), a mosquito-transmitted single-stranded rna (ssrna) flavivirus, causes human disease of variable severity. we investigated toll-like receptor 7-deficient (tlr7(-/-)) and myeloid differentiation factor 88-deficient (myd88(-/-)) mice, which both have defective recognition of ssrna, and found increased viremia and susceptibility to lethal wnv infection. despite increased tissue concentrations of most innate cytokines, cd45(+) leukocytes and cd11b(+) macrophages failed to home ...200919200759
a small-molecule dengue virus entry inhibitor.the incidence of dengue fever epidemics has increased dramatically over the last few decades. however, no vaccine or antiviral therapies are available. therefore, the need for safe and effective antiviral drugs has become imperative. the entry of dengue virus into a host cell is mediated by its major envelope (e) protein. the crystal structure of the e protein reveals a hydrophobic pocket that is presumably important for low-ph-mediated membrane fusion. high-throughput docking with this hydropho ...200919223625
novel imino sugar derivatives demonstrate potent antiviral activity against flaviviruses.imino sugars, such as n-butyl-deoxynojirimycin and n-nonyl-deoxynojirimycin (nndnj), are glucose analogues that selectively inhibit cellular alpha-glucosidase i and ii in the endoplasmic reticulum and exhibit antiviral activities against many types of enveloped viruses. although these molecules have broad-spectrum antiviral activity, their development has been limited by a lack of efficacy and/or selectivity. we have previously reported that a dnj derivative with a hydroxylated cyclohexyl side c ...200919223639
nucleotide sequences and modifications that determine rig-i/rna binding and signaling activities.cytoplasmic viral rnas with 5' triphosphates (5'ppp) are detected by the rna helicase rig-i, initiating downstream signaling and alpha/beta interferon (ifn-alpha/beta) expression that establish an antiviral state. we demonstrate here that the hepatitis c virus (hcv) 3' untranslated region (utr) rna has greater activity as an immune stimulator than several flavivirus utr rnas. we confirmed that the hcv 3'-utr poly(u/uc) region is the determinant for robust activation of rig-i-mediated innate immu ...200919224987
a new flavivirus and a new vector: characterization of a novel flavivirus isolated from uranotaenia mosquitoes from a tropical rain forest.a novel flavivirus was isolated from uranotaenia mashonaensis, a mosquito genus not previously known to harbor flaviviruses. mosquitoes were caught in the primary rain forest of the taï national park, côte d'ivoire. the novel virus, termed nounané virus (nouv), seemed to grow only on c6/36 insect cells and not on vertebrate cells. typical enveloped flavivirus-like particles of 60 to 65 nm in diameter were detected by electron microscopy in the cell culture supernatant of infected cells. the full ...200919224998
[flavivirus encephalitis].the member of the genus flavivirus family flaviviridae are arthropod-transmitted viruses. this genus includes vector-borne neurotropic viruses such as the tick-borne encephalitis virus serocomplex and the japanese encephalitis virus serocomplex. flavivirus encephalitis is the generic term for encephalitis caused by viruses belonging to this genus. the japanese encephalitis virus is still active in japan, and the tick-borne encephalitis virus is prevalent in hokkaido, the northern region of japan ...200919235464
identification and analysis of putative promoter motifs in flavivirus genome.the genus flavivirus comprises medically significant pathogenic virus; causing several infections in humans worldwide. flavivirus genomes are 10-11 kb approximately and encode both structural and non structural region. the non structural region plays fundamental role in the stability, regulation and cell cycle of virus. the complete genomes of 26 flavivirus were used for identification of promoter motifs through in silico approaches. the promoter sequences were encoded in merely 16 viruses and 1 ...200819238240
identification of novel target sites and an inhibitor of the dengue virus e protein.dengue and related flaviviruses represent a significant global health threat. the envelope glycoprotein e mediates virus attachment to a host cell and the subsequent fusion of viral and host cell membranes. the fusion process is driven by conformational changes in the e protein and is an essential step in the virus life cycle. in this study, we analyzed the pre-fusion and post-fusion structures of the dengue virus e protein to identify potential novel sites that could bind small molecules, which ...200919241120
atomic structure reveals the unique capsid organization of a dsrna virus.for most dsrna viruses, the genome-enclosing capsid comprises 120 copies of a single capsid protein (cp) organized into 60 icosahedrally equivalent dimers, generally identified as 2 nonsymmetricallyinteracting cp molecules with extensive lateral contacts. the crystal structure of a partitivirus, penicillium stoloniferum virus f (psv-f), reveals a different organization, in which the cp dimer is related by almost-perfect local 2-fold symmetry, forms prominent surface arches, and includes extensiv ...200919246376
role of antibodies in controlling dengue virus infection.the incidence and disease burden of arthropod-borne flavivirus infections have dramatically increased during the last decades due to major societal and economic changes, including massive urbanization, lack of vector control, travel, and international trade. specifically, in the case of dengue virus (denv), the geographical spread of all four serotypes throughout the subtropical regions of the world has led to larger and more severe outbreaks. many studies have established that recovery from inf ...200919261353
tyrosine 78 of premembrane protein is essential for assembly of west nile virus.flavivirus premembrane (prm) protein plays an important role in conformational folding of the envelope (e) protein and protects it against premature fusion in acidic vesicles of the golgi network. currently, molecular determinants on the prm protein ectodomain which mediate critical steps during the flavivirus assembly process are poorly characterized. in this study, bioinformatics analysis and alanine scanning mutagenesis showed that the amino acid triplet valine 76, tyrosine 78 and glycine 79 ...200919264649
on a mouse monoclonal antibody that neutralizes all four dengue virus serotypes.the flavivirus envelope glycoprotein (e) is responsible for viral attachment and entry by membrane fusion. its ectodomain is the primary target of the humoral immune response. in particular, the c-terminal ig-like domain iii of e, which is exposed at the surface of the viral particle, forms an attractive antigen for raising protective monoclonal antibodies (mab). 9f12, a mouse mab raised against a dengue virus (denv) serotype 2 recombinant domain iii, cross-reacts with corresponding domains from ...200919264660
virus-specific cytolytic antibodies to nonstructural protein 1 of japanese encephalitis virus effect reduction of virus output from infected cells.we demonstrate the presence of nonstructural protein 1 (ns1)-specific antibodies in a significant proportion of convalescent-phase human serum samples obtained from a cohort in an area where japanese encephalitis virus (jev) is endemic. sera containing antibodies to ns1 but not those with antibodies to other jev proteins, such as envelope, brought about complement-mediated lysis of jev-infected bhk-21 cells. target cells infected with a recombinant poxvirus expressing jev ns1 on the cell surface ...200919264772
new drug targets for hepatitis c and other flaviviridae viruses.the flaviviridae family comprises the genus flavivirus, hepacivirus and pestivirus. these viruses are responsible for considerable human and animal disease and mortality worldwide. flaviviruses cause a range of acute febrile illnesses along with encephalitic or haemorrhagic diseases. chronic hepatitis c virus (hcv) infection is the most important hepacivirus human disease and remains a global health threat with nearly 200 million carriers worldwide. current treatment consists in the use of pegin ...200919275702
crystal structure of a methyltransferase from a no-known-vector flavivirus.presently known flaviviruses belong to three major evolutionary branches: tick-borne viruses, mosquito-borne viruses and viruses with no known vector. here we present the crystal structure of the yokose virus methyltransferase at 1.7a resolution, the first structure of a methyltransferase of a flavivirus with no known vector. structural comparison of three methyltransferases representative of each of the flavivirus branches shows that fold and structures are closely conserved, most differences b ...200919275894
sequence signatures in envelope protein may determine whether flaviviruses produce hemorrhagic or encephalitic syndromes.we analyzed the envelope proteins in pathogenic flaviviruses to determine whether there are sequence signatures associated with the tendency of viruses to produce hemorrhagic disease (h-viruses) or encephalitis (e-viruses). we found that, at the position corresponding to the glycosylated asn-67 in dengue virus, asparagine (asn) occurs in all seven viral species that cause hemorrhagic disease in humans. furthermore, asn was extremely rare at position 67 in six flaviviruses that cause encephalitis ...200919283462
spontaneous splenic rupture due to dengue fever: report of two cases.dengue is a febrile illness caused by flavivírus and mainly transmitted by the mosquito aedes aegypiti which have been a serious epidemic in rio de janeiro. in most of cases it was a self limited disease. we report two cases of a serious and rare complication of this viral infection.200819287846
evidence of a humoral response to a novel protein warf4 embedded in the west nile virus ns4b gene encoded by an alternative open reading frame.west nile virus (wnv) is a flavivirus that is maintained in a bird-mosquito transmission cycle. humans, horses and other non-avian vertebrates are usually incidental hosts. however, wnv is a neurotropic virus, which requires an efficient humoral response for the control of a neuroinvasive infection. the wnv genome encodes three structural (capsid, premembrane/membrane and envelope) and seven non-structural proteins. bioinformatic analysis performed on the wnv genomes detected a conserved alterna ...200919288027
crm1-mediated nuclear export of dengue virus rna polymerase ns5 modulates interleukin-8 induction and virus production.although all established functions of dengue virus ns5 (nonstructural protein 5) occur in the cytoplasm, its nuclear localization, mediated by dual nuclear localization sequences, is essential for virus replication. here, we have determined the mechanism by which ns5 can localize in the cytoplasm to perform its role in replication, establishing for the first time that it is able to be exported from the nucleus by the exportin crm1 and hence can shuttle between the nucleus and cytoplasm. we defin ...200919297323
helices alpha2 and alpha3 of west nile virus capsid protein are dispensable for assembly of infectious virions.the internal hydrophobic sequence within the flaviviral capsid protein (protein c) plays an important role in the assembly of infectious virions. here, this sequence was analyzed in a west nile virus lineage i isolate (crow v76/1). an infectious cdna clone was constructed and used to introduce deletions into the internal hydrophobic domain which comprises helix alpha2 and part of the loop intervening helices alpha2 and alpha3. in total, nine capsid deletion mutants (4 to 14 amino acids long) wer ...200919297470
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
evaluation of an epitope-blocking enzyme-linked immunosorbent assay for the diagnosis of west nile virus infections in humans.an epitope-blocking enzyme-linked immunosorbent assay (b-elisa) was evaluated for the diagnosis of west nile virus (wnv) infections in humans. sera from patients diagnosed with wnv infections from an outbreak in 2003 in colorado and from patients diagnosed with dengue virus infections from mexico and thailand were tested with the b-elisa. the b-elisas were performed using the wnv-specific monoclonal antibody (mab) 3.1112g and the flavivirus-specific mab 6b6c-1. although the wnv-specific b-elisa ...200919321694
a replicon trans-packaging system reveals the requirement of nonstructural proteins for the assembly of bovine viral diarrhea virus (bvdv) virion.a selective trans-packaging system was developed to produce and isolate bovine viral diarrhea virus (bvdv) pseudo-particles with complementing reporter replicons and their packaging proteins expressed in trans with recombinant vaccinia virus. the encapsidation of replicon rns3-5b was dependent not only on the in trans expression of structural proteins c, e(rns), e1 and e2, but also the nonstructural proteins, p7 and contiguous precursor ns2-3-4a. nonstructural p7, ns4b, ns5a or ns5b could be exp ...200919327808
safety concerns about ccr5 as an antiviral target.clinical trials of ccr5 antagonists attest to their efficacy and tolerance in hiv treatment. however, there has been debate on their long-term safety because of the role of ccr5 in innate immunity. this review highlights gaps in our understanding of epidemiology of infections that are modulated by ccr5, in particular, in hiv-infected individuals.200919339952
isolation and characterization of a new mosquito flavivirus, quang binh virus, from vietnam.in recent years, a number of flaviviruses that replicate only in an arthropod host have been discovered and characterized. we describe here the isolation and characterization of a new mosquito-only flavivirus in this group. the virus was isolated from culex tritaeniorhyncus mosquitoes collected in vietnam in 2002 and was found to be genetically different from mosquito flaviviruses described previously. we propose the isolate be named quang binh virus.200919347244
identification of a novel determinant for membrane association in hepatitis c virus nonstructural protein 4b.nonstructural protein 4b (ns4b) plays an essential role in the formation of the hepatitis c virus (hcv) replication complex. it is a relatively poorly characterized integral membrane protein predicted to comprise four transmembrane segments in its central portion. here, we describe a novel determinant for membrane association represented by amino acids (aa) 40 to 69 in the n-terminal portion of ns4b. this segment was sufficient to target and tightly anchor the green fluorescent protein to cellul ...200919357161
a japanese encephalitis virus vaccine candidate strain is attenuated by decreasing its interferon antagonistic ability.japanese encephalitis virus (jev) is a mosquito-borne flavivirus that causes acute encephalitis with high mortality in humans. to understand the virus-host interactions that influence jev virulence, we determined the lethality of a neurovirulent (rp-9) and an attenuated (rp-2ms) variant of jev in several immunodeficient mice strains. the attenuated phenotype of rp-2ms was completely lost in stat-1-deficient mice, but its virulence was only slightly increased in mice lacking the components of ada ...200919366580
glyceraldehyde-3-phosphate dehydrogenase (gapdh) interaction with 3' ends of japanese encephalitis virus rna and colocalization with the viral ns5 protein.replication of the japanese encephalitis virus (jev) genome depends on host factors for successfully completing their life cycles; to do this, host factors have been recruited and/or relocated to the site of viral replication. glyceraldehyde-3-phosphate dehydrogenase (gapdh), a cellular metabolic protein, was found to colocalize with viral rna-dependent rna polymerase (ns5) in jev-infected cells. subcellular fractionation further indicated that gapdh remained relatively constant in the cytosol, ...200919368702
pathogenesis of flavivirus infections: using and abusing the host cell.flaviviruses, such as the dengue virus and the west nile virus, are emerging arthropod-borne viruses that represent an immense global health problem. considerable progress has been made in understanding flavivirus structure and replication strategies, but only now are the complex molecular interactions between the virus and host cell starting to be unraveled. in this review, we discuss the ongoing efforts toward elucidating the molecular mechanisms that allow flaviviruses to manipulate host cell ...200919380111
composition and three-dimensional architecture of the dengue virus replication and assembly sites.positive-strand rna viruses are known to rearrange cellular membranes to facilitate viral genome replication. the biogenesis and three-dimensional organization of these membranes and the link between replication and virus assembly sites is not fully clear. using electron microscopy, we find dengue virus (denv)-induced vesicles, convoluted membranes, and virus particles to be endoplasmic reticulum (er)-derived, and we detect double-stranded rna, a presumed marker of rna replication, inside virus- ...200919380115
the polypyrimidine tract-binding protein is required for efficient dengue virus propagation and associates with the viral replication machinery.the polypyrimidine tract-binding protein (ptb) functions primarily as an ires trans-acting factor in the propagation of hepatitis c virus and picornaviruses. ptb interacts with secondary structures within the 3'- and 5'-untranslated regions of these viral genomes to mediate efficient ires-mediated viral translation. ptb has also been reported to bind to the untranslated region of the single-stranded rna dengue virus (denv), suggesting a similar function for ptb in flaviviruses. indeed small inte ...200919380576
human monoclonal antibodies against west nile virus induced by natural infection neutralize at a postattachment step.west nile virus (wnv) is a neurotropic flavivirus that is now a primary cause of epidemic encephalitis in north america. studies of mice have demonstrated that the humoral immune response against wnv limits primary infection and protects against a secondary challenge. the most-potent neutralizing mouse monoclonal antibodies (mabs) recognize an epitope on the lateral ridge of domain iii (diii-lr) of the envelope (e) protein. however, studies with serum from human patients show that antibodies aga ...200919386704
activation of the west nile virus ns3 protease: molecular dynamics evidence for a conformational selection mechanism.the flaviviral nonstructural 3 protease (ns3pro) is essential for virus replication and is therefore a pharmaceutically relevant target to fight dengue and west nile virus (wnv). ns3pro is a chymotrypsin-like serine protease which requires a polypeptide cofactor (ns2b) for activation. recent x-ray crystallography studies have led to the suggestion that the substrate binds to the two-component ns2b-ns3pro enzyme by an induced-fit mechanism. here, multiple explicit water molecular dynamics simulat ...200919388022
complement and its role in protection and pathogenesis of flavivirus infections.the complement system is a family of serum and cell surface proteins that recognize pathogen-associated molecular patterns, altered-self ligands, and immune complexes. activation of the complement cascade triggers several antiviral functions including pathogen opsonization and/or lysis, and priming of adaptive immune responses. in this review, we will examine the role of complement activation in protection and/or pathogenesis against infection by flaviviruses, with an emphasis on experiments wit ...200819388173
the risk of dengue transmission by blood during a 2004 outbreak in cairns, australia.dengue virus (denv) is a flavivirus transmitted by the aedes mosquito. the related arbovirus, west nile virus, has been shown to be transfusion transmitted, which, added to the four recorded dengue transfusion-associated cases, indicates that denv is also transfusion transmitted. the purpose of this study was to assess the risk of transfusion-transmitted denv during a 2004 outbreak in the australian city of cairns.200919389025
identification of cellular proteome modifications in response to west nile virus infection.flaviviruses are positive-stranded rna viruses that are a public health problem because of their widespread distribution and their ability to cause a variety of diseases in humans. west nile virus is a mosquito-borne member of this genus and is the etiologic agent of west nile encephalitis. clinical manifestations of west nile virus infection are diverse, and their pathogenic mechanisms depend on complex virus-cell interactions. in the present work, we used proteomics technology to analyze early ...200919395707
conservation and variability of west nile virus proteins.west nile virus (wnv) has emerged globally as an increasingly important pathogen for humans and domestic animals. studies of the evolutionary diversity of the virus over its known history will help to elucidate conserved sites, and characterize their correspondence to other pathogens and their relevance to the immune system. we describe a large-scale analysis of the entire wnv proteome, aimed at identifying and characterizing evolutionarily conserved amino acid sequences. this study, which used ...200919401763
changing patterns of west nile virus transmission: altered vector competence and host susceptibility.west nile virus (wnv) is a flavivirus (flaviviridae) transmitted between culex spp. mosquitoes and avian hosts. the virus has dramatically expanded its geographic range in the past ten years. increases in global commerce, climate change, ecological factors and the emergence of novel viral genotypes likely play significant roles in the emergence of this virus; however, the exact mechanism and relative importance of each is uncertain. previously wnv was primarily associated with febrile illness of ...200919406093
application of antibodies against nonstructural protein 2b of dengue serotype 2 virus induced by dna immunisation or recombinant protein ns 2b immunisation in balb/c mice.to investigate the structure and function of nonstructural (ns) protein 2b of the dengue serotype 2 virus (dv2) during infection, polyclonal antibodies (abs) against dv2 ns2b were prepared by immunisation with ns2b protein or by dna immunisation. the full-length ns2b gene was cloned and inserted into the prokaryotic expression vector pqe31, resulting in a vector, named pqe-ns2b, or into the eukaryotic expression vector pcaggs-p7, resulting in the vector pcag-ns2b. the pqe-ns2b vector was transfe ...201019406165
induction of specific and flavivirus--cross-reactive ctls by immunization with a single dengue virus-derived ctl epitope peptide.specificities of cytotoxic t lymphocyte (ctl) effector cells induced in balb/c mouse by immunization with the single modified ctl epitope peptide derived from ns3 of dengue virus types 1 and 3, or that of dengue virus types 2 and 4 were examined. the effector cells included ctls specific for the epitope peptide used for immunization and those cross-reactive to epitope peptides of other flaviviruses. a ctl clone, 2f7, was established from the effector cells. the clone 2f7 was specific for the epi ...200919427342
a pyrazolotriazolopyrimidinamine inhibitor of bovine viral diarrhea virus replication that targets the viral rna-dependent rna polymerase.[7-[3-(1,3-benzodioxol-5-yl)propyl]-2-(2-furyl)-7h-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] (lz37) was identified as a selective inhibitor of in vitro bovine viral diarrhea virus (bvdv) replication. the ec(50) values for inhibition of bvdv-induced cytopathic effect (cpe) formation, viral rna synthesis and production of infectious virus were 4.3+/-0.7microm, 12.9+/-1microm and 5.8+/-0.6microm, respectively. lz37 proved inactive against the hepatitis c virus and the flavivirus yello ...200919428605
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
polypyrimidine tract-binding protein influences negative strand rna synthesis of dengue virus.flavivirus non-structural protein 4a (ns4a) induces membrane rearrangements to form viral replication complex and functions as interferon antagonist. however, other non-structural roles of ns4a protein in relation to virus life-cycle are poorly defined. this study elucidated if dengue virus (denv) ns4a protein interacts with host proteins and contributes to viral pathogenesis by screening human liver cdna yeast-two-hybrid library. our study identified polypyrimidine tract-binding protein (ptb) a ...200919450550
cyclosporine inhibits flavivirus replication through blocking the interaction between host cyclophilins and viral ns5 protein.although flaviviruses cause significant human diseases, no effective therapy is currently available. host factors essential for viral replication are potential targets for antiviral development. here we report that cyclophilins (cyps), a family of cellular peptidyl-prolyl isomerases (ppiases), play a role in flavivirus replication. huh-7.5 cells with knockdown of different isoforms of cyp were less efficient than parental cells in supporting flavivirus replication, including west nile virus (wnv ...200919451286
[population interactions of west nile virus (flaviviridae, flavivirus) with arthropode vectors, vertebrates, humans in the middle and low belts of volga delta in 2001-2006].the population interactions of west nile virus in the middle and lower regions of the volga delta in 2001-2006 were studied. the authors established major species of the mosquitoes anopheles messeae, an. hyrcanus, culex piplens, cx modestus, coquilletidia richiardii in anthropogenic biocenoses and an. hyrcanus, coq. richiardii in the natural ones; vertebrates - crows (corvidae) and domestic animals in the anthropogenic biocenoses and cormorants in the natural ones. the ticks hyalomma marginatum ...200919459411
molecular evolution of dengue viruses: contributions of phylogenetics to understanding the history and epidemiology of the preeminent arboviral disease.dengue viruses (denv) are the most important arboviral pathogens in tropical and subtropical regions throughout the world, putting at risk of infection nearly a third of the global human population. evidence from the historical record suggests a long association between these viruses and humans. the transmission of denv includes a sylvatic, enzootic cycle between nonhuman primates and arboreal mosquitoes of the genus aedes, and an urban, endemic/epidemic cycle between aedes aegypti, a mosquito w ...200919460319
japanese encephalitis virus ns2b-ns3 protease induces caspase 3 activation and mitochondria-mediated apoptosis in human medulloblastoma cells.japanese encephalitis virus (jev) causes severe neurological diseases with a high fatality rate. clinical, neurophysiological and radiological features of japanese encephalitis je patients showed that jev infection resulted in widespread involvement of the nervous system, including thalamus, basal ganglia, brainstem, cerebellum, cerebral cortex and spinal cord. in this study, we characterized the apoptotic effect of jev infection and its viral proteins on the te671 human medulloblastoma cells. j ...200919463724
hepatitis c virus ns4b carboxy terminal domain is a membrane binding domain.hepatitis c virus (hcv) induces membrane rearrangements during replication. all hcv proteins are associated to membranes, pointing out the importance of membranes for hcv. non structural protein 4b (ns4b) has been reported to induce cellular membrane alterations like the membranous web. four transmembrane segments in the middle of the protein anchor ns4b to membranes. an amphipatic helix at the amino-terminus attaches to membranes as well. the carboxy-terminal domain (ctd) of ns4b is highly cons ...200919467155
clinical evaluation of highly pathogenic tick-borne flavivirus infection in the mouse model.the objective of this study was to evaluate the feasibility of using clinical parameters to demonstrate disease progression and differentiate between omsk hemorrhagic fever virus (ohfv) and russian spring-summer encephalitis virus (rssev) infection in the mouse model. adult c57bl/6 and balb/c mice were infected with either ohfv or rssev by footpad inoculation and their temperature, body weight, clinical signs complete blood count, and blood chemistries were evaluated for up to 15 days post-infec ...200919475605
surveillance of arboviruses in spanish wetlands: detection of new flavi- and phleboviruses.the presence of viruses in arthropods in spain has been studied over 5 years. flaviviruses similar to cell-fusing agent, sequences of a flavivirus related to those transmitted by mosquitoes, and a phlebovirus similar to naples and toscana viruses were detected. their potential human or animal pathogenicity should be studied.201019485777
the zoonotic flaviviruses of southern, south-eastern and eastern asia, and australasia: the potential for emergent viruses.the genus flaviviridae comprises about 70 members, of which about 30 are found in southern, south-eastern and eastern asia and australasia. these include major pathogens such as japanese encephalitis (je), west nile (wn), murray valley encephalitis (mve), tick-borne encephalitis, kyasanur forest disease virus, and the dengue viruses. other members are known to be associated with mild febrile disease in humans, or with no known disease. in addition, novel flaviviruses continue to be discovered, a ...200919486319
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