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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
a novel nucleoside analog, 1-beta-d-ribofuranosyl-3-ethynyl-[1,2,4]triazole (etar), exhibits efficacy against a broad range of flaviviruses in vitro.antiviral therapies are urgently needed to control emerging flaviviruses such as dengue, west nile, and yellow fever. ribavirin (rbv) has shown activity against flaviviruses in cultured cells, but efficacy in animal models has generally been poor. in a preliminary screen of novel, synthetic 1-beta-d-ribofuranosyl-azole analogs, two compounds, 1-beta-d-ribofuranosyl-3-ethynyl-[1,2,4]triazole (etar) and 1-beta-d-ribofuranosyl-4-ethynyl-[1,3]imidazole (im18), significantly reduced the replication o ...201020416341
rna interference modulates replication of dengue virus in drosophila melanogaster cells.mosquito-borne dengue virus (denv, genus flavivirus) has emerged as a major threat to global human health in recent decades, and novel strategies to contain the escalating dengue fever pandemic are urgently needed. rna interference (rnai) induced by exogenous small interfering rnas (sirnas) has shown promise for treatment of flavivirus infections in hosts and prevention of transmission by vectors. however, the impact of rnai triggered by authentic virus infection on replication of denv, or any f ...201020420715
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
japanese encephalitis virus down-regulates thioredoxin and induces ros-mediated ask1-erk/p38 mapk activation in human promonocyte cells.japanese encephalitis virus (jev), a mosquito-borne flavivirus, causes severe neurological disease with high mortality. molecular mechanisms of jev pathogenesis such as upstream apoptotic processes and pathways are not yet completely resolved or understood. in this study, jev replication in human promonocyte cells induced time-dependent apoptosis and activated virus dose-dependent caspases 3, 8 and 9. proteomic analysis demonstrated up- and down-regulated (more or less than 1.5-fold) proteins in ...201020430109
dengue and primary care: a tale of two cities. 201020431782
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
sentinel birds in wild-bird resting sites as potential indicators for west nile virus infections in germany.west nile virus (wnv) is a mosquito-transmitted flavivirus with wild birds as its natural hosts. ravens, falcons and jays are highly susceptible for wnv and develop deadly encephalitis, while other bird species undergo only subclinical infections. migratory birds are efficient vectors for geographic spreading of wnv. until now, wnv infections have not been diagnosed in germany, but infections in humans and horses have occurred recently in austria, hungary and italy. to investigate potential wnv ...201020437062
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
role of bc loop residues in structure, function and antigenicity of the west nile virus envelope protein receptor-binding domain iii.site-directed mutagenesis of residues in the bc loop (residues 329-333) of the envelope (e) protein domain iii in a west nile virus (wnv) infectious clone and in plasmids encoding recombinant wnv and dengue type 2 virus domain iii proteins demonstrated a critical role for residues in this loop in the function and antigenicity of the e protein. this included a strict requirement for the tyrosine at residue 329 of wnv for virus viability and e domain iii folding. the absence of an equivalent resid ...201020447672
intrinsic disorder in the core proteins of flaviviruses.hepatitis c virus and related viruses in the flaviviridae family (such as dengue virus, yellow fever virus or west nile virus) are amongst the most important human pathogens, causing substantial morbidity and mortality world-wide. the production of viral progeny in flaviviridae is orchestrated by the small, multifunctional core protein, which coats and condenses the viral genomic rna during nucleocapsid formation. in addition to their structural role, mounting experimental evidence links core pr ...201020450480
role of host cell factors in flavivirus infection: implications for pathogenesis and development of antiviral drugs.the genus flavivirus contains approximately 70 arthropod-borne enveloped rna viruses many of which cause severe human and in some cases, animal disease. they include dengue virus, yellow fever virus, west nile virus, japanese encephalitis virus, and tick-borne encephalitis virus. hundreds of thousands of deaths due to flavivirus infections occur each year, many of which are unpreventable due to lack of availability of appropriate vaccines and/or antiviral drugs. flaviviruses exploit the cytoplas ...201020452379
transmission of west nile virus by culex quinquefasciatus say infected with culex flavivirus izabal.the natural history and potential impact of mosquito-specific flaviviruses on the transmission efficiency of west nile virus (wnv) is unknown. the objective of this study was to determine whether or not prior infection with culex flavivirus (cxfv) izabal altered the vector competence of cx. quinquefasciatus say for transmission of a co-circulating strain of west nile virus (wnv) from guatemala.201020454569
severity of acute hepatitis and its outcome in patients with dengue fever in a tertiary care hospital karachi, pakistan (south asia).liver injury due to dengue viral infection is not uncommon. acute liver injury is a severe complicating factor in dengue, predisposing to life-threatening hemorrhage, disseminated intravascular coagulation (dic) and encephalopathy. therefore we sought to determine the frequency of hepatitis in dengue infection and to compare the outcome (length of stay, in hospital mortality, complications) between patients of dengue who have mild/moderate (alt 23-300 iu/l) v/s severe acute hepatitis (alt > 300 ...201020459677
enhancement of anti-diii antibodies by the c3d derivative p28 results in lower viral titers and augments protection in mice.antibodies generated against west nile virus (wnv) during infection are essential for controlling dissemination. recent studies have demonstrated that epitopes in all three domains of the flavivirus envelope protein (e) are targets for neutralizing antibodies, with determinants in domain iii (diii) eliciting antibodies with strong inhibitory properties. in order to increase the magnitude and quality of the antibody response against the wnv e protein, dna vaccines with derivatives of the wnv e ge ...201020462412
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
screening of mosquitoes using sybr green i-based real-time rt-pcr with group-specific primers for detection of flaviviruses and alphaviruses in taiwan.surveillance for infectious agents carried by mosquitoes is important for predicting the risk of vector-borne infectious diseases. in this study, a method was established to mass-screen mosquitoes for viral infections. the assay detected the viral load of 4 dengue virus (denv) serotypes (denv-1, denv-2, denv-3, and denv-4), the japanese encephalitis virus (jev), the sindbis virus and the chikungunya virus at 1pfu/ml (determined by real-time rt-pcr) in 36.64-43.45 cycles. this method was applied ...201020471427
timing of cd8+ t cell responses in relation to commencement of capillary leakage in children with dengue.immune activation is a feature of dengue hemorrhagic fever (dhf) and cd8+ t cell responses in particular have been suggested as having a role in the vasculopathy that characterizes this disease. by phenotyping cd8+ t cells (cd38+/hla-dr+, cd38+/ki-67+, or hla-dr+/ki-67+) in serial blood samples from children with dengue, we found no evidence of increased cd8+ t cell activation prior to the commencement of resolution of viremia or hemoconcentration. investigations with mhc class i tetramers to de ...201020483770
characterization of the gxxxg motif in the first transmembrane segment of japanese encephalitis virus precursor membrane (prm) protein.the interaction between prm and e proteins in flavivirus-infected cells is a major driving force for the assembly of flavivirus particles. we used site-directed mutagenesis to study the potential role of the transmembrane domains of the prm proteins of japanese encephalitis virus (jev) in prm-e heterodimerization as well as subviral particle formation. alanine insertion scanning mutagenesis within the gxxxg motif in the first transmembrane segment of jev prm protein affected the prm-e heterodime ...201020492732
identification of palmatine as an inhibitor of west nile virus.in this study, we investigated the specific inhibition of west nile virus (wnv) ns2b-ns3 protease and viral propagation by palmatine, a chemical compound from coptis chinensis franch. it was demonstrated that palmatine could inhibit wnv ns2b-ns3 protease activity in an uncompetitive manner, with a 50% inhibitory concentration (ic(50)) of 96 microm. palmatine suppressed wnv without detectable cytotoxicity (a 50% effective concentration [ec(50)] of 3.6 microm and a 50% cytotoxicity concentration [ ...201020496087
dengue antibodies in polish travellers returning from the tropics. evaluation of serological tests.dengue is a viral disease caused by an rna virus of the genus flavivirus, family flaviviridae, occurring as four serotypes (den-1, -2, -3, -4). it is transmitted to humans by the aedes mosquitoes, mainly a. aegypti. the occurrence of dengue is strictly related with their preferred breeding areas. dengue endemic regions are inhabited by some 2.5 billion people. 50-100 million cases of dengue fever and up to 1 million cases of dengue haemorrhagic fever are noted worldwide in more than 100 countrie ...201020496327
mosquito (diptera: culicidae) surveillance for arboviruses in an area endemic for west nile (lineage rabensburg) and tahyna viruses in central europe.six viral isolates were obtained from 23,243 female mosquitoes (examined in 513 pools) belonging to 16 species and collected along the lower reaches of the dyje river in south moravia (czech republic, central europe) during 2006-2008: five isolates of orthobunyavirus tahyna (tahv, california group, family bunyaviridae: three isolations from aedes vexans (meigen), one from ae. sticticus (meigen), one from culex modestus ficalbi); and one isolation of flavivirus west nile (wnv, japanese encephalit ...201020496595
transfusion transmission of highly prevalent commensal human viruses.anellovirus species torque teno virus (ttv), torque teno mini virus (ttmv), and torque teno midi virus (ttmdv) and flavivirus gbv-c are highly prevalent and genetically diverse chronic human viral infections that have not yet been associated with disease.201020497515
dimerization of the hepatitis c virus nonstructural protein 4b depends on the integrity of an aminoterminal basic leucine zipper.the hepatitis c virus (hcv) nonstructural (ns) protein 4b is known for protein-protein interactions with virus and host cell factors. only little is known about the corresponding protein binding sites and underlying molecular mechanisms. recently, we have predicted a putative basic leucine zipper (bzip) motif within the aminoterminal part of ns4b. the aim of this study was to investigate the importance of this ns4b bzip motif for specific protein-protein interactions. we applied in silico approa ...201020506268
viral reorganization of the secretory pathway generates distinct organelles for rna replication.many rna viruses remodel intracellular membranes to generate specialized sites for rna replication. how membranes are remodeled and what properties make them conducive for replication are unknown. here we show how rna viruses can manipulate multiple components of the cellular secretory pathway to generate organelles specialized for replication that are distinct in protein and lipid composition from the host cell. specific viral proteins modulate effector recruitment by arf1 gtpase and its guanin ...201020510927
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
inhibition of dengue virus by an ester prodrug of an adenosine analog.dengue virus (denv) is the most prevalent mosquito-borne viral pathogen that infects humans. neither a vaccine nor an antiviral therapy is currently available for denv. here, we report an adenosine nucleoside prodrug that potently inhibits denv replication both in cell culture and in a denv mouse model. nitd449 (2'-c-acetylene-7-deaza-7-carbamoyladenosine) was initially identified as a parental compound that inhibits all four serotypes of denv with low cytotoxicity. however, in vivo pharmacokine ...201020516277
evidence for ribosomal frameshifting and a novel overlapping gene in the genomes of insect-specific flaviviruses.flaviviruses have a positive-sense, single-stranded rna genome of approximately 11 kb, encoding a large polyprotein that is cleaved to produce approximately 10 mature proteins. cell fusing agent virus, kamiti river virus, culex flavivirus and several recently discovered flaviviruses have no known vertebrate host and apparently infect only insects. we present compelling bioinformatic evidence for a 253-295 codon overlapping gene (designated fifo) conserved throughout these insect-specific flavivi ...201020097399
the ns5 protein of the virulent west nile virus ny99 strain is a potent antagonist of type i interferon-mediated jak-stat signaling.flaviviruses transmitted by arthropods represent a tremendous disease burden for humans, causing millions of infections annually. all vector-borne flaviviruses studied to date suppress host innate responses to infection by inhibiting alpha/beta interferon (ifn-alpha/beta)-mediated jak-stat signal transduction. the viral nonstructural protein ns5 of some flaviviruses functions as the major ifn antagonist, associated with inhibition of ifn-dependent stat1 phosphorylation (py-stat1) or with stat2 d ...201020106931
novel inhibitors of dengue virus methyltransferase: discovery by in vitro-driven virtual screening on a desktop computer grid.dengue fever is a viral disease that affects 50-100 million people annually and is one of the most important emerging infectious diseases in many areas of the world. currently, neither specific drugs nor vaccines are available. here, we report on the discovery of new inhibitors of the viral ns5 rna methyltransferase, a promising flavivirus drug target. we have used a multistage molecular docking approach to screen a library of more than 5 million commercially available compounds against the two ...201020108931
mechanism and specificity of a symmetrical benzimidazolephenylcarboxamide helicase inhibitor.this study examines the effects of 1-n,4-n-bis[4-(1h-benzimidazol-2-yl)phenyl]benzene-1,4-dicarboxamide ((bip)(2)b) on the ns3 helicase encoded by the hepatitis c virus (hcv). molecular beacon-based helicase assays were used to show that (bip)(2)b inhibits the ability of hcv helicase to separate a variety of rna and dna duplexes with half-maximal inhibitory concentrations ranging from 0.7 to 5 microm, depending on the nature of the substrate. in single turnover assays, (bip)(2)b only inhibited u ...201020108979
west nile virus: is a vaccine needed?west nile virus (wnv) is a neurotropic flavivirus that was associated with sporadic outbreaks of meningoencephalitis in africa and the middle east until 1999, when a more virulent strain emerged in the us that caused thousands of infections among humans and horses, with reported fatality rates between 10 and 50%. although the epidemiology of wnv is changing into a more endemic pattern in the us, and the incidence of neuroinvasive disease is decreasing, the long-term effects of resolved wnv infec ...201020112163
infection control guidelines for prevention of health care-associated transmission of hepatitis b and c viruses.viral hepatitis was first identified as an occupational hazard for health care workers more than 60 years ago. for the past few decades, hepatitis b has been one of the most significant occupational infectious risks for health care providers. with the increasing prevalence of hepatitis c infections around the world, occupational transmission of this flavivirus from infected patients to their providers has also become a significant concern. several factors influence the risk for occupational bloo ...201020123445
an inactivated vero cell-grown japanese encephalitis vaccine formulated with advax, a novel inulin-based adjuvant, induces protective neutralizing antibody against homologous and heterologous flaviviruses.advax is a polysaccharide-based adjuvant that potently stimulates vaccine immunogenicity without the increased reactogenicity seen with other adjuvants. this study investigated the immunogenicity of a novel advax-adjuvanted vero cell culture candidate vaccine against japanese encephalitis virus (jev) in mice and horses. the results showed that, in mice, a two-immunization, low-dose (50 ng jev antigen) regimen with adjuvanted vaccine produced solid neutralizing immunity comparable to that elicite ...201020130134
effects of forced egg retention on the temporal progression of west nile virus infection in culex pipiens quinquefasciatus (diptera: culicidae).environmental factors that impact the biology of mosquito vectors can have epidemiological implications. lack of oviposition sites facilitated by environmental factors such as temperature and drought can often force culex spp. mosquitoes to retain their eggs. culex pipiens quinquefasciatus say were fed blood meals containing west nile virus (wnv; family flaviviridae, genus flavivirus) and either allowed to oviposit or forced to retain their eggs through different time points postinfection (9, 13 ...201020146856
arboviruses in blood donors: a study in the amazon region and in a small city with a dengue outbreak. 201020149157
minocycline differentially modulates macrophage mediated peripheral immune response following japanese encephalitis virus infection.japanese encephalitis virus (jev) is a neurotropic flavivirus that is the causative agent of a major mosquito-borne encephalitis in the world. evasion of peripheral immune system facilitates the entry of the virus into the central nervous system (cns) where it causes extensive neuronal inflammatory damage that leads to death or severe neuropschychiatric sequel in survivors. it has been proposed that after entry into the body, the virus is carried into the cns by peripheral immune cells that act ...201020153075
a high-throughput assay using dengue-1 virus-like particles for drug discovery.dengue virus (denv) is a mosquito-borne flavivirus responsible for 50-100 million human infections each year. the development of denv chemotherapy requires high-throughput screening (hts) assays. a dengue virus-like particle (vlp) has been constructed using viral structural proteins to package a renilla luciferase reporter replicon. vlp could be produced by either the sequential electroporation of the replicon rnas and the structural gene rnas or by electroporating replicon rna into a stable cel ...201020153777
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
field evaluation of commercial immunoglobulin m antibody capture elisa diagnostic tests for the detection of japanese encephalitis virus infection among encephalitis patients in nepal.japanese encephalitis (je) is a devastating disease with high rates of death and disability that occurs particularly in resource-limited, rural regions of asia. simple, accurate and inexpensive diagnostics tests are vital for quantifying the burden of illness. this field study evaluated two commercial je immunoglobulin m antibody capture (mac) elisa kits using samples from routine je surveillance.201020346721
higher catalytic efficiency of n-7-methylation is responsible for processive n-7 and 2'-o methyltransferase activity in dengue virus.methyltransferases (mtases) from the genus flavivirus encode both n-7 and 2'-o activities needed for type 1 (m(7)gpppnm) cap structure formation. we performed kinetic studies to understand the mechanisms of its progressive n-7 and 2'-o methylations. sequential n-7 to 2'-o methylation occurred via a random bi bi and processive mechanism that does not involve enzyme-rna dissociation. analyses of steady state kinetic parameters showed that n-7 precedes 2'-o methylation as it turnovers rna faster (k ...201020350738
safety and pharmacokinetics of single intravenous dose of mgawn1, a novel monoclonal antibody to west nile virus.west nile virus (wnv) is a neurotropic flavivirus that can cause debilitating diseases, such as encephalitis, meningitis, or flaccid paralysis. we report the safety, pharmacokinetics, and immunogenicity of a recombinant humanized monoclonal antibody (mgawn1) targeting the e protein of wnv in a phase 1 study, the first to be performed on humans. a single intravenous infusion of saline or of mgawn1 at escalating doses (0.3, 1, 3, 10, or 30 mg/kg of body weight) was administered to 40 healthy volun ...201020350945
interplay of rna elements in the dengue virus 5' and 3' ends required for viral rna replication.dengue virus (denv) is a member of the flavivirus genus of positive-sense rna viruses. denv rna replication requires cyclization of the viral genome mediated by two pairs of complementary sequences in the 5' and 3' ends, designated 5' and 3' cyclization sequences (5'-3' cs) and the 5' and 3' upstream of aug region (5'-3' uar). here, we demonstrate that another stretch of six nucleotides in the 5' end is involved in denv replication and possibly genome cyclization. this new sequence is located do ...201020357095
japanese encephalitis virus utilizes the canonical pathway to activate nf-kappab but it utilizes the type i interferon pathway to induce major histocompatibility complex class i expression in mouse embryonic fibroblasts.flaviviruses have been shown to induce cell surface expression of major histocompatibility complex class i (mhc-i) through the activation of nf-kappab. using ikk1(-/-), ikk2(-/-), nemo(-/-), and ikk1(-/-) ikk2(-/-) double mutant as well as p50(-/-) rela(-/-) crel(-/-) triple mutant mouse embryonic fibroblasts infected with japanese encephalitis virus (jev), we show that this flavivirus utilizes the canonical pathway to activate nf-kappab in an ikk2- and nemo-, but not ikk1-, dependent manner. nf ...201020357096
influence of pr-m cleavage on the heterogeneity of extracellular dengue virus particles.during dengue virus replication, an incomplete cleavage of the envelope glycoprotein prm, generates a mixture of mature (prm-less) and prm-containing, immature extracellular particles. in this study, sequential immunoprecipitation and cryoelectron microscopy revealed a third type of extracellular particles, the partially mature particles, as the major prm-containing particles in a dengue serotype 2 virus. changes in the proportion of viral particles in the pr-m junction mutants exhibiting altere ...201020519400
evaluation of replivax wn, a single-cycle flavivirus vaccine, in a non-human primate model of west nile virus infection.west nile virus (wnv) causes serious neurologic disease, but no licensed vaccines are available to prevent this disease in humans. we have developed replivax wn, a single-cycle flavivirus with an expected safety profile superior to other types of live-attenuated viral vaccines. in this report we describe studies examining replivax wn safety, potency, and efficacy in a non-human primate model of wnv infection. a single immunization of four rhesus macaques with replivax wn was safe and elicited de ...201020519618
the aetiology, clinical presentations and outcome of febrile encephalopathy in children in papua new guinea.febrile encephalopathy, defined as fever, seizures and/or altered consciousness, is a common presentation in children in tropical developing countries. outcomes range from complete recovery through varying degrees of neurological disability which slowly resolve or remain permanent to death from either the acute illness or complications. whilst bacterial meningitis accounts for a proportion of children affected, the aetiology in many remains unclear but includes malaria and probably viral encepha ...201020522297
sequential immunization with heterologous chimeric flaviviruses induces broad-spectrum cross-reactive cd8+ t cell responses.flavivirus vaccines based on chimerivax technology contain the nonstructural genes of the yellow fever vaccine and the premembrane and envelope genes of heterologous flaviviruses, such as japanese encephalitis and west nile viruses. these chimeric vaccines induce both humoral and cell-mediated immunity. mice were vaccinated with yellow fever, chimeric japanese encephalitis virus (yf/je), or chimeric west nile virus (yf/wn) vaccines, followed by a secondary homologous or heterologous vaccination; ...201020536361
chimeric antibodies against tick-borne encephalitis virus.two chimeric antibodies (ch) 13d6 and 10c2 against the glycoprotein e of tick-borne encephalitis virus (tbev) were constructed by fusing variable regions of murine monoclonal antibodies (mabs) 13d6 and 10c2 to human constant regions. monovalent analogues of these antibodies in format of single-chain antibodies (scfv or sc) were developed, as well. the ch13d6, ch10c2, sc13d6 and sc10c2 exhibited binding characteristics similar to parental mabs. only the ch13d6 and sc13d6 were able to neutralize t ...201020538092
virus-induced ca2+ influx extends survival of west nile virus-infected cells.west nile virus (wnv) infection leads to rapid and sustained ca(2+) influx. this influx was observed with different strains of wnv and in different types of cells. entry during virion endocytosis as well as through calcium channels contributed to the ca(2+) influx observed in wnv-infected cells. ca(2+) influx was not detected after infection with vesicular stomatitis virus (vsv) and occurred only through endocytosis in sindbis virus-infected cells. caspase 3 cleavage and activation of several ki ...201020538858
structure determination of the top-loop of the conserved 3'-terminal secondary structure in the genome of flaviviruses.to what extent small differences in rna sequences (mutations) can have a profound impact on biology remains an intriguing question. this effect can be studied by using untranslated rna regions as a model. we have studied the influence of mutations on the structure of an rna hairpin that occurs in the 3'-untranslated region (utr) of flaviviridae, and is known to have a large impact on the vector dependency of flaviviruses. three related rna sequences were studied by nmr spectroscopy. the selected ...201020540055
[investigation of west nile virus in central nervous system infections of unknown etiology in ankara, turkey].arthropod-borne viral infections have recently gained considerable attention and importance as re-emerging infections in a global scale. west nile virus (wnv), a member of flaviviridae, is an enveloped positive strand rna virus that is usually transmitted to humans by the bite of culicine mosquitoes. although the majority of the human infections are asymptomatic, wnv may also cause febrile and neuro-invasive diseases. seroprevalence data from turkey indicate that wnv activity is present in centr ...201020549960
flavivirus encephalitis: pathological aspects of mouse and other animal models.encephalitic flaviviruses are important arthropod-borne pathogens of humans and other animals. in particular, the recent emergence of the west nile virus (wnv) and japanese encephalitis virus (jev) in new geographic areas has caused a considerable public health alert and international concern. among the experimental in vivo models of wnv and jev infection, mice and other laboratory rodents are the most thoroughly studied and well-characterized systems, having provided data that are important for ...201020551474
nonstructural ns1 proteins of several mosquito-borne flavivirus do not inhibit tlr3 signaling.flaviviruses are single-stranded positive rna viruses that replicate through double stranded rna (dsrna) intermediates. these dsrna may be recognized as pathogen-associated molecular patterns by cellular receptors including membrane-bound toll-like receptor 3 (tlr3) and cytosolic helicases rig-i and mda5. dsrna stimulation results in signaling cascades converging to activation of interferon (ifn) regulatory factor 3 (irf3) and to transcriptional activation of several interferon stimulated genes, ...201020554300
tick-borne encephalitis virus delays interferon induction and hides its double-stranded rna in intracellular membrane vesicles.tick-borne encephalitis virus (tbev) (family flaviviridae, genus flavivirus) accounts for approximately 10,000 annual cases of severe encephalitis in europe and asia. here, we investigated the induction of the antiviral type i interferons (ifns) (alpha/beta ifn [ifn-alpha/beta]) by tbev. using strains neudörfl, hypr, and absettarov, we demonstrate that levels of ifn-beta transcripts and viral rna are strictly correlated. moreover, ifn induction by tbev was dependent on the transcription factor i ...201020554782
advances in flavivirus research. 201020565287
niaid workshop on flavivirus immunity.on september 16, 2009, the national institute of allergy and infectious diseases (niaid), part of the u.s. national institutes of health, convened a workshop to discuss current knowledge of t- and b-cell immune epitopes for members of the flavivirus genus (family flaviviridae), and how this information could be used to increase our basic understanding of host-pathogen interactions and/or advance the development of new or improved vaccines and diagnostics for these pathogens. b-cell and t-cell re ...201020565288
meta-analysis of all immune epitope data in the flavivirus genus: inventory of current immune epitope data status in the context of virus immunity and immunopathology.a meta-analysis was performed in order to inventory the immune epitope data related to viruses in the genus flavivirus. nearly 2000 epitopes were captured from over 130 individual flavivirus-related references identified from pubmed and reported as of september 2009. this report includes all epitope structures and associated immune reactivity from the past and current literature, including: the epitope distribution among pathogens and related strains, the epitope distribution among different pat ...201020565291
seronegative naturally acquired west nile virus encephalitis in a renal and pancreas transplant recipient.west nile virus (wnv), a single-stranded rna flavivirus, has spread across the united states since arriving in 1999. while asymptomatic or self-limited in a majority of patients, wnv can cause a severe neuroinvasive disease, which occurs more often in transplant recipients with chronic immunosuppression. diagnosis of acute wnv infection usually relies on serologic identification of immunoglobulin m (igm) specific for the virus. we report a fatal case of naturally acquired wnv encephalitis in a r ...201020576021
factors associated with mosquito pool positivity and the characterization of the west nile viruses found within louisiana during 2007.west nile virus (wnv) is an arbovirus of public health importance in the genus flavivirus, a group of positive sense rna viruses. the ns3 gene has a high level of substitutions and is phylogenetically informative. likewise, substitutions in the envelope region have been postulated to enable viruses to subvert immune responses. analysis of these genes among isolates from positive mosquitoes collected in louisiana illustrates the variation present in the regions and provides improved insight to a ...201020579348
a short n-terminal peptide motif on flavivirus nonstructural protein ns1 modulates cellular targeting and immune recognition.flavivirus ns1 is a versatile nonstructural glycoprotein, with intracellular ns1 functioning as an essential cofactor for viral replication and cell surface and secreted ns1 antagonizing complement activation. even though ns1 has multiple functions that contribute to virulence, the genetic determinants that regulate the spatial distribution of ns1 in cells among different flaviviruses remain uncharacterized. here, by creating a panel of west nile virus-dengue virus (wnv-denv) ns1 chimeras and si ...201020592095
molecular epidemiology of saint louis encephalitis virus in the brazilian amazon: genetic divergence and dispersal.saint louis encephalitis virus (slev), a member of the genus flavivirus (family flaviviridae), is an encephalitogenic arbovirus broadly distributed in the americas. phylogenetic analysis based on the full-length e gene sequences obtained for 30 brazilian slev strains was performed using different methods including bayesian and relaxed molecular clock approaches. a new genetic lineage was suggested, hereafter named genotype viii, which co-circulates with the previously described genotype v in the ...201020592112
false-positive transcription-mediated amplification assay detection of west nile virus in blood from a patient with viremia caused by an usutu virus infection.detection of west nile virus (wnv) by nucleic acid amplification technology (naat) is used widely to screen blood and organ donations in areas where wnv is endemic. we report a false-positive result of a wnv transcription-mediated amplification assay (tma) in a patient with viremia that was caused by usutu virus, a mosquito-borne flavivirus.201020592138
environmental and biological factors influencing culex pipiens quinquefasciatus (diptera: culicidae) vector competence for west nile virus.interactions between environmental and biological factors affect the vector competence of culex pipiens quinquefasciatus for west nile virus. three age cohorts from two cx. p. quinquefasciatus colonies were fed blood containing a low- or high-virus dose, and each group was held at two different extrinsic incubation temperatures (eit) for 13 days. the colonies differed in the way that they responded to the effects of the environment on vector competence. the effects of mosquito age on aspects of ...201020595491
rapid purification of recombinant dengue and west nile virus envelope domain iii proteins by metal affinity membrane chromatography.arthropod-borne flaviviruses such as dengue virus (denv) and west nile virus (wnv) pose significant health threats to the global community. due to escalating numbers of denv and wnv infections worldwide, development of an effective vaccine remains a global health priority. as flavivirus envelope domain iii (diii) protein is highly immunogenic and capable of inducing neutralizing antibodies against wild-type virus, it is both a potential protein subunit vaccine candidate and a suitable diagnostic ...201020600950
library screening by fragment-based docking.we review our computational tools for high-throughput screening by fragment-based docking of large collections of small molecules. applications to six different enzymes, four proteases, and two protein kinases, are presented. remarkably, several low-micromolar inhibitors were discovered in each of the high-throughput docking campaigns. probable reasons for the lack of submicromolar inhibitors are the tiny fraction of chemical space covered by the libraries of available compounds, as well as the ...201019718684
searching for west nile virus (wnv) in greece.west nile virus (wnv), a mosquito-borne flavivirus, has increasingly become a concern in both america and europe due to its complex and unpredictable lifecycle. transfusion-associated transmission of the wnv has been well documented during the last few years. this study aimed to detect the presence of wnv in: (i) cerebrospinal fluid (csf) specimens derived from aseptic meningitis cases in greece and (ii) greek blood donations. a total of 115 csf specimens from patients suffering from aseptic men ...201019719473
usutu virus in wild birds in northern italy.usutu virus (usuv) infection was diagnosed in two free-living blackbirds and in three captive owls belonging to two different species in northern italy in the summers of 2006-2008. diagnosis was established by immunohistochemistry and rt-pcr. rt-pcr was performed on frozen and on paraffin-embedded tissues (pet), respectively. from the frozen samples a partial sequence of the putative usuv e and ns1 proteins (1229 bp) was determined, whereas partial sequences of the putative ns3 (278 bp) and ns5 ...201019720475
a membranotropic region in the c-terminal domain of hepatitis c virus protein ns4b interaction with membranes.we have identified a membrane-active region in the hcv ns4b protein by studying membrane rupture induced by a ns4b-derived peptide library on model membranes. this segment corresponds to one of two previously predicted amphipathic helix and define it as a new membrane association domain. we report the binding and interaction with model membranes of a peptide patterned after this segment, peptide ns4b(h2), and show that ns4b(h2) strongly partitions into phospholipid membranes, interacts with them ...201019631190
structure-based virtual screening for novel inhibitors of japanese encephalitis virus ns3 helicase/nucleoside triphosphatase.japanese encephalitis (je) is a significant cause of human morbidity and mortality throughout asia and africa. vaccines have reduced the incidence of je in some countries, but no specific antiviral therapy is currently available. the ns3 protein of japanese encephalitis virus (jev) is a multifunctional protein combining protease, helicase and nucleoside 5'-triphosphatase (ntpase) activities. the crystal structure of the catalytic domain of this protein has recently been solved using a roentgenog ...201019863664
a trans-complementing recombination trap demonstrates a low propensity of flaviviruses for intermolecular recombination.intermolecular recombination between the genomes of closely related rna viruses can result in the emergence of novel strains with altered pathogenic potential and antigenicity. although recombination between flavivirus genomes has never been demonstrated experimentally, the potential risk of generating undesirable recombinants has nevertheless been a matter of concern and controversy with respect to the development of live flavivirus vaccines. as an experimental system for investigating the abil ...201019864381
preclinical and clinical development of yfv 17d-based chimeric vaccines against dengue, west nile and japanese encephalitis viruses.dengue viruses (denv), west nile virus (wnv) and japanese encephalitis virus (jev) are major global health and growing medical problems. while a live-attenuated vaccine exists since decades against the prototype flavivirus, yellow fever virus (yfv), there is an urgent need for vaccines against dengue or west nile diseases, and for improved vaccines against japanese encephalitis. live-attenuated chimeric viruses were constructed by replacing the genes coding for premembrane (prm) and envelope (e) ...201019808029
biochemical characterization of the (nucleoside-2'o)-methyltransferase activity of dengue virus protein ns5 using purified capped rna oligonucleotides (7me)gpppac(n) and gpppac(n).the flavivirus rna genome contains a conserved cap-1 structure, (7me)gpppa(2'ome)g, at the 5' end. two mrna cap methyltransferase (mtase) activities involved in the formation of the cap, the (guanine-n7)- and the (nucleoside-2'o)-mtases (2'o-mtase), reside in a single domain of non-structural protein ns5 (ns5mtase). this study reports on the biochemical characterization of the 2'o-mtase activity of ns5mtase of dengue virus (ns5mtase(dv)) using purified, short, capped rna substrates ((7me)gpppac( ...201019776234
zoonotic tick-borne flaviviruses.tick-borne flaviviruses are among the medically most important arboviruses in europe and asia. tick-borne encephalitis causes between 10,000 and 15,000 human cases every year in both continents. besides this disease there are several other tick-borne flaviviruses which may be of local medical importance, and which are less known, but may be important as differential diagnosis. among them are louping-ill disease which is present mainly on the british islands, omsk hemorrhagic fever, which is prev ...201019765917
zoonotic mosquito-borne flaviviruses: worldwide presence of agents with proven pathogenicity and potential candidates of future emerging diseases.an update on the mosquito-borne flavivirus species including certain subtypes, as listed in the eighth report of the international committee on taxonomy of viruses, is given. special emphasis is placed on viruses which have been shown to cause diseases in animals, and viruses for which no pathogenicity has been proven yet. several recent examples (usutu virus and lineage-2 west nile virus in central europe, zika virus in micronesia) have shown that sources providing information on such scientifi ...201019762169
genomics and evolution of aedes-borne flaviviruses.we analysed the complete coding sequences of all recognized species of aedes-borne flavivirus, including previously uncharacterized viruses within the yellow fever virus (yfv), spondweni virus (spov) and dengue virus (denv) groups. two major phylogenetic lineages were revealed: one included the yfv and entebbe bat virus groups, and the other included the denv, spov and culex-borne flavivirus groups. this analysis supported previous evidence that culex-borne flaviviruses have evolved from ancestr ...201019741066
meningitis determined by oligosymptomatic dengue virus type 3 infection: report of a case.dengue infection is a mosquito-borne disease caused by a flavivirus, and is recognized in over 100 countries with 2.5 billion people living in areas of risk. neurological manifestations such as encephalitis, myelitis, guillain-barré syndrome, cranial nerve palsies, neuromyelitis optica, and encephalomyelitis have been recognized as clinical consequences of dengue infection. meningitis is a rare complication. we report the case of a 24-year-old woman who presented with fever, headache, and nuchal ...201019501535
serologic surveillance for west nile virus and other flaviviruses in febrile patients, encephalitic patients, and asymptomatic blood donors in northern mexico.a clinical and serological investigation was performed to determine the presence of west nile virus (wnv) among febrile and encephalitic patients in northern mexico. in addition, asymptomatic blood donors were serologically assayed for wnv to determine the seroprevalence of wnv in the general population. the study cohort consisted of 1432 individuals (588 febrile patients, 44 encephalitic patients, and 800 asymptomatic blood donors). all subjects were negative for wnv igm. sixty subjects were re ...201019492946
flavivirus rna in phlebotomine sandflies.sandfly-transmitted phleboviruses, such as toscana, sandfly fever sicilian, and sandfly fever naples, can cause human disease and circulate at high rates in mediterranean countries. previous studies have also established that viruses other than phleboviruses may be detected in and isolated from sand flies. the recent detection and isolation (in a large variety of mosquito species) of insect-only flaviviruses related to cell fusing agent virus has indicated that the latter is not an evolutionary ...201019492949
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
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
epizootology and experimental infection of yokose virus in bats.to reveal whether bats serve as an amplifying host for yokose virus (yokv), we conducted a serological survey and experimentally infected fruit bats with yokv isolated from microbats in japan. yokv belongs to the entebbe bat virus group of vector unknown group within the genus flavivirus and family flaviviridae. to detect antibodies against yokv, we developed an enzyme-linked immunosorbent assay (elisa) using biotinylated anti-bat igg rabbit sera. serological surveillance was conducted with samp ...201018789527
confirmed exposure to tick-borne encephalitis virus and probable human cases of tick-borne encephalitis in central/northern anatolia, turkey.tick-borne encephalitis virus (tbev) is the aetiological agent of tick-borne encephalitis (tbe), a potentially fatal central nervous system infection of humans. tbe is endemic in many areas of europe and asia; however, very scarce data on tbev activity are available from turkey. we aimed to identify tbev exposure in healthy blood donors and the impact of tbev in central nervous system infections in central/northern anatolia. two-thousand four hundred and fifty four sera, collected from blood don ...201120604912
seroepidemiology of nine zoonoses in viljujsk, republic of sakha (northeastern siberia, russian federation).a seroepidemiology survey of nine zoonoses was carried out in 2007 on 90 healthy adult volunteers in viljujsk, a northern city in the republic of sakha (eastern siberia). the seroprevalence of lyme borreliosis was 3.3% by immunofluorescence. none of the subjects displayed a positive enzyme-linked immunosorbent assay/western blot result for alveolar or cystic echinococcosis. the seroprevalence of toxocariasis by western blot was 4.4%, and 8.9% of the subjects had anti-toxoplasma igg. by enzyme-li ...201120575641
surveillance for west nile virus in wild birds from northern europe.a total of 1935 migratory birds from 104 different species were captured in southeastern sweden in 2005-2006 and tested for antibodies against west nile virus (wnv). overall, 46 birds (2.4%; binomial confidence limits, 1.8-3.2) were positive by blocking-elisa, but only 2 (0.10%; binomial confidence limits, 0.0-0.4) had antibodies detectable by both blocking-elisa and wnv neutralization test. elisa-positive birds included long- and short-distance migrants likely exposed to wnv while wintering in ...201120518642
meteorological and hydrological influences on the spatial and temporal prevalence of west nile virus in culex mosquitoes, suffolk county, new york.the factors determining the spatial and temporal distribution of west nile virus (family flaviviridae, genus flavivirus, wnv) activity are not well understood. here, we explore the effects of hydrological and meteorological conditions on wnv infection among culex genus mosquitoes collected during 2001-2009 in suffolk county, long island, ny. we show that wnv infection rates in assayed pools of culex mosquitoes are associated in both space and time with hydrological and meteorological variability ...201121845947
winter biology of wetland mosquitoes at a focus of eastern equine encephalomyelitis virus transmission in alabama, usa.at temperate latitudes, vectors and pathogens must possess biological mechanisms for coping with cold temperatures and surviving from one transmission season to the next. mosquitoes that overwinter in the adult stage have been proposed as winter maintenance hosts for certain arboviruses. in the cases of west nile virus (family flaviviridae, genus flavivirus) and st. louis encephalitis virus (family flaviviridae, genus flavivirus), discovery of infected overwintering females lends support to this ...201121936314
flavivirus-induced antibody cross-reactivity.dengue viruses (denv) cause countless human deaths each year, whilst west nile virus (wnv) has re-emerged as an important human pathogen. there are currently no wnv or denv vaccines licensed for human use, yet vaccines exist against other flaviviruses. to investigate flavivirus cross-reactivity, sera from a human cohort with a history of vaccination against tick-borne encephalitis virus (tbev), japanese encephalitis virus (jev) and yellow fever virus (yfv) were tested for antibodies by plaque re ...201121900425
a conserved peptide in west nile virus ns4a protein contributes to proteolytic processing and is essential for replication.the west nile virus strain kunjin virus (wnv(kun)) ns4a protein is a multifunctional protein involved in membrane proliferation, stimulation of cellular pathways, and evasion of host defense and is a major component of the wnv(kun) rna replication complex. we identified a highly conserved region ((120)p-e-p-e(123)) upstream of the viral protease dibasic cleavage site and investigated whether this motif was required for wnv(kun) replication. single point mutations to alanine and a pepe deletion m ...201121880777
new japanese encephalitis vaccines: alternatives to production in mouse brain.japanese encephalitis virus (jev), a flavivirus maintained in a zoonotic cycle and transmitted by the mosquito culex tritaeniorhynchus, causes epidemics of encephalitis throughout much of asia. resident populations, including short- or long-term visitors to enzootic regions, are at risk of infection and disease. for the past several decades, killed viral vaccines prepared in tissue culture or mouse brain have been used effectively to immunize travelers and residents of enzootic countries. cost, ...201121434803
first serological evidence of west nile virus activity in horses in serbia.abstract west nile virus (wnv), the most widely distributed flavivirus worldwide, has lately reemerged in europe, causing worrisome outbreaks in humans and horses. serological analysis by enzyme-linked immunoassay and plaque reduction neutralization test showed for the first time in serbia that 12% of 349 horses presented specific neutralizing wnv antibodies, which in one case also cross-neutralized usutu virus (usuv). this is the first time that anti-usuv high neutralizing antibody titers are r ...201121438694
purification and concentration of non-infectious west nile virus-like particles and infectious virions using a pseudo-affinity cellufine sulfate column.affinity column chromatography is a promising method for the purification of flavivirus particles that can supplement or potentially replace diafiltration and sucrose density centrifugation. in this study, the purification of west nile virus (wnv) antigens via cellufine sulfate column chromatography was examined. virus-like particles (vlps) produced by the expression of the prm and e genes were separated from most of the contaminant proteins with 0.2-0.4m nacl, but still retained their spherical ...201121440004
duck egg-drop syndrome caused by byd virus, a new tembusu-related flavivirus.since april 2010, a severe outbreak of duck viral infection, with egg drop, feed uptake decline and ovary-oviduct disease, has spread around the major duck-producing regions in china. a new virus, named byd virus, was isolated in different areas, and a similar disease was reproduced in healthy egg-producing ducks, infecting with the isolated virus. the virus was re-isolated from the affected ducks and replicated well in primary duck embryo fibroblasts and vero cells, causing the cytopathic effec ...201121455312
seroprevalence of west nile virus in feral horses on sheldon national wildlife refuge, nevada, united states.we screened 1,397 feral horses (equus caballus) on sheldon national wildlife refuge, nevada, united states, for igm and igg against flavivirus during 2004-2006, 2008, and 2009. positive serum samples were tested for neutralizing antibodies to west nile virus (wnv) and st. louis encephalitis virus (slev). one animal was positive for antibody against wnv in 2004, but all others tested in 2004-2006 were negative. in 2008 and 2009, we found evidence of increasing seropositive horses with age, wherea ...201121460023
the f1 motif of dengue virus polymerase ns5 is involved in promoter-dependent rna synthesis.the mechanism by which viral rna-dependent rna polymerases (rdrp) specifically amplify viral genomes is still unclear. in the case of flaviviruses, a model has been proposed that involves the recognition of an rna element present at the viral 5' untranslated region, stem-loop a (sla), that serves as a promoter for ns5 polymerase binding and activity. here, we investigated requirements for specific promoter-dependent rna synthesis of the dengue virus ns5 protein. using mutated purified ns5 recomb ...201121471248
flavidb: a data mining system for knowledge discovery in flaviviruses with direct applications in immunology and vaccinology.the flavivirus genus is unusually large, comprising more than 70 species, of which more than half are known human pathogens. it includes a set of clinically relevant infectious agents such as dengue, west nile, yellow fever, and japanese encephalitis viruses. although these pathogens have been studied exten-sively, safe and efficient vaccines lack for the majority of the flaviviruses. we have assembled a database that combines antigenic data of flaviviruses, specialized analysis tools, and workf ...201122126825
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
Quantitative comparison of the cross-protection induced by tick-borne encephalitis virus vaccines based on European and Far Eastern virus subtypes.Tick-borne encephalitis virus (TBEV) is a flavivirus of wide geographic distribution and the causative agent of tick-borne encephalitis (TBE), an infection of the central nervous system. TBE has the highest incidence rate in Russia, where locally produced as well as Western European vaccines for the prevention of TBE are available. The Western European vaccines are based on TBE viruses that belong to the European subtype, while the Russian vaccines are based on Far Eastern subtype viruses. The q ...201122178103
Autophagy is involved in the early step of Japanese encephalitis virus infection.Japanese encephalitis virus (JEV), an enveloped Flavivirus with a positive-sense RNA genome, causes acute encephalitis with high mortality in humans. We used a virulent (RP-9) and an attenuated (RP-2ms) JEV strain to assess the role of autophagy in JEV infection. By monitoring the levels of lipidated LC3, we found that autophagy was induced in human NT-2 cells infected with RP-2ms, especially at the late stage, and to a lesser extent with RP-9. The induction of autophagy by rapamycin increased v ...201121946213
west nile virus replication requires fatty acid synthesis but is independent on phosphatidylinositol-4-phosphate lipids.west nile virus (wnv) is a neurovirulent mosquito-borne flavivirus, which main natural hosts are birds but it also infects equines and humans, among other mammals. as in the case of other plus-stranded rna viruses, wnv replication is associated to intracellular membrane rearrangements. based on results obtained with a variety of viruses, different cellular processes have been shown to play important roles on these membrane rearrangements for efficient viral replication. as these processes are re ...201121949814
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