Publications

dynamics of the cd8 t-cell response following yellow fever virus 17d immunization.	management of yellow fever is focused on the prevention of illness by the use of the yellow fever virus (yfv) 17d vaccine. the role of neutralizing antibodies in protection is generally accepted with yfv-specific t cells likely contributing to the control of viral replication. we studied cd8(+) t-cell responses to four defined human leucocyte antigen-b35-restricted epitopes in yfv vaccine recipients as a model of the kinetics of cytotoxic t-lymphocyte responses to an acute human viral infection. ...	2009	19740333
focus on flaviviruses: current and future drug targets.	infection by mosquito-borne flaviviruses (family flaviviridae) is increasing in prevalence worldwide. the vast global, social and economic impact due to the morbidity and mortality associated with the diseases caused by these viruses necessitates therapeutic intervention. there is currently no effective clinical treatment for any flaviviral infection. therefore, there is a great need for the identification of novel inhibitors to target the virus life cycle.	2009	20165556
usutu virus infection in a patient who underwent orthotropic liver transplantation, italy, august-september 2009.	we report a case of usutu virus (usuv)-related illness in a patient that underwent an orthotropic liver transplant (olt). post transplant, the patient developed clinical signs of a possible neuroinvasive disease with a significant loss of cerebral functions. usuv was isolated in vero e6 cells from a plasma sample obtained immediately before the surgery, and usuv rna was demonstrated by rt-pcr and sequencing. this report enlarges the panel of emerging mosquito-borne flavivirus-related disease in ...	2009	20070935
seasonal patterns for entomological measures of risk for exposure to culex vectors and west nile virus in relation to human disease cases in northeastern colorado.	we examined seasonal patterns for entomological measures of risk for exposure to culex vectors and west nile virus (family flaviviridae, genus flavivirus, wnv) in relation to human wnv disease cases in a five-county area of northeastern colorado during 2006-2007. studies along habitat/elevation gradients in 2006 showed that the seasonal activity period is shortened and peak numbers occur later in the summer for culex tarsalis coquillett females in foothills-montane areas >1600 m compared with pl ...	2009	19960707
relationship between distance from major larval habitats and abundance of adult mosquitoes in semiarid plains landscapes in colorado.	we examined the relationship between distance from major larval habitats and abundance of adult mosquitoes in the semiarid plains landscape characteristic of eastern colorado. mosquito collection was conducted from late june to early august 2007 and included trap locations at distances ranging from <10 m up to 20-150 m and 160-373 m from three major larval habitats: one area along a river corridor and two small reservoirs. the study yielded 65,140 mosquitoes of 14 species, and five species were ...	2009	19960672
complement protein c1q reduces the stoichiometric threshold for antibody-mediated neutralization of west nile virus.	virus neutralization is governed by the number of antibodies that bind a virion during the cellular entry process. cellular and serum factors that interact with antibodies have the potential to modulate neutralization potency. although the addition of serum complement can increase the neutralizing activity of antiviral antibodies in vitro, the mechanism and significance of this augmented potency in vivo remain uncertain. herein, we show that the complement component c1q increases the potency of ...	2009	19837377
the flavivirus ns5 protein is a true rna guanylyltransferase that catalyzes a two-step reaction to form the rna cap structure.	the 5'-end of the flavivirus genome harbors a methylated (m7)gpppa(2'ome) cap structure, which is generated by the virus-encoded rna triphosphatase, rna (guanine-n7) methyltransferase, nucleoside 2'-o-methyltransferase, and rna guanylyltransferase. the presence of the flavivirus guanylyltransferase activity in ns5 has been suggested by several groups but has not been empirically proven. here we provide evidence that the n-terminus of the flavivirus ns5 protein is a true rna guanylyltransferase. ...	2009	19850911
dengue virus ns5 inhibits interferon-alpha signaling by blocking signal transducer and activator of transcription 2 phosphorylation.	type i interferons (interferon [ifn]-alpha/beta) are key mediators of innate antiviral responses. inhibition of ifn-mediated signal transduction by dengue viruses (denvs), mosquito-borne flaviviruses of immense global health importance, probably plays a crucial role in determining the outcome of the virus-host interaction. understanding the molecular basis of ifn antagonism by denv would therefore provide critical insight into disease pathogenesis and new opportunities for development of antivir ...	2009	19754307
efficient assembly and secretion of recombinant subviral particles of the four dengue serotypes using native prm and e proteins.	flavivirus infected cells produce infectious virions and subviral particles, both of which are formed by the assembly of prm and e envelope proteins and are believed to undergo the same maturation process. dengue recombinant subviral particles have been produced in cell cultures with either modified or chimeric proteins but not using the native forms of prm and e.	2009	20016834
dengue surveillance in preparation for field vaccine trials.	preparations for dengue vaccine trials as well as vaccine introduction strategies require laboratory-based surveillance on an international and coordinated level. the pediatric dengue vaccine initiative (pdvi) has developed an international consortium of field sites in latin america and asia. these sites conduct community- based and enhanced passive laboratory-based surveillance of dengue fever. through this consortium, pdvi is facilitating harmonized laboratory-based surveillance processes, so ...	2009	19800559
generation of congenic mouse strains by introducing the virus-resistant genes, mx1 and oas1b, of feral mouse-derived inbred strain msm/ms into the common strain c57bl/6j.	mx1 (myxovirus resistance protein) and oaslb (oligoadenylate synthetase-1), induced by type 1 interferon (ifn), play a role in early antiviral innate immunity by inhibiting the replication of viruses. in mice, mx1 and oas1b confer resistance to the infection of orthomyxoviruses including influenza viruses and flaviviruses including west nile viruses, respectively. laboratory mice have been used to study the mechanisms of the pathogenesis of these virus infections; however, it is possible that th ...	2009	19827744
rna-dependent rna polymerases from flaviviruses and picornaviridae.	flaviviruses and picornaviruses are positive-strand rna viruses that encode the rna-dependent rna polymerase (rdrp) required for replicating the viral genome in infected cells. because of their specific and essential role in the virus life cycle, rdrps are prime targets for antiviral drugs. recent structural data have shed light on the different strategies used by rdrps from flaviviruses and picornaviridae to initiate rna polymerization. new details about the catalytic mechanism, the role of met ...	2009	19910184
an adenosine nucleoside inhibitor of dengue virus.	dengue virus (denv), a mosquito-borne flavivirus, is a major public health threat. the virus poses risk to 2.5 billion people worldwide and causes 50 to 100 million human infections each year. neither a vaccine nor an antiviral therapy is currently available for prevention and treatment of denv infection. here, we report a previously undescribed adenosine analog, nitd008, that potently inhibits denv both in vitro and in vivo. in addition to the 4 serotypes of denv, nitd008 inhibits other flavivi ...	2009	19918064
viruses within the flaviviridae decrease cd4 expression and inhibit hiv replication in human cd4+ cells.	viral infections alter host cell homeostasis and this may lead to immune evasion and/or interfere with the replication of other microbes in coinfected hosts. two flaviviruses are associated with a reduction in hiv replication or improved survival in hiv-infected people (dengue virus (dv) and gb virus type c (gbv-c)). gbv-c infection and expression of the gbv-c nonstructural protein 5a (ns5a) and the dv ns5 protein in cd4(+) t cells inhibit hiv replication in vitro. to determine whether the inhib ...	2009	19923460
the yellow fever virus vaccine induces a broad and polyfunctional human memory cd8+ t cell response.	the live yellow fever vaccine (yf-17d) offers a unique opportunity to study memory cd8(+) t cell differentiation in humans following an acute viral infection. we have performed a comprehensive analysis of the virus-specific cd8(+) t cell response using overlapping peptides spanning the entire viral genome. our results showed that the yf-17d vaccine induces a broad cd8(+) t cell response targeting several epitopes within each viral protein. we identified a dominant hla-a2-restricted epitope in th ...	2009	19933869
capturing a flavivirus pre-fusion intermediate.	during cell entry of flaviviruses, low endosomal ph triggers the rearrangement of the viral surface glycoproteins to a fusion-active state that allows the release of the infectious rna into the cytoplasm. in this work, west nile virus was complexed with fab fragments of the neutralizing mab e16 and was subsequently exposed to low ph, trapping the virions in a pre-fusion intermediate state. the structure of the complex was studied by cryo-electron microscopy and provides the first structural glim ...	2009	19956725
is culex modestus (diptera: culicidae), vector of west nile virus, spreading in the dombes area, france?	as a main vector of west nile (wn) virus (family flaviviridae, genus flavivirus) in europe, culex modestus ficalbi (diptera: culicidae) is commonly found in delta regions, lakes, and ponds. the dombes area is located along one of the main corridors of bird migrations in france and lies 300 km north of the camargue region, a frequent focus of wn virus circulation. it is an important breeding, wintering, and stopover site for many bird species that are putative carriers of viruses of different kin ...	2009	19960670
arrival and establishment of aedes japonicus japonicus (diptera: culicidae) in iowa.	the arrival and establishment of aedes (finlaya) japonicus japonicus (theobald) (diptera: culicidae) in iowa are reported. in total, 518 wild adult specimens were collected through the statewide mosquito and mosquito-borne virus surveillance program in 2007 and 2008. specimens were collected with new jersey light traps, co2-baited cdc light traps, grass infusion-baited gravid traps, and mosquito magnet traps located in 12 counties in central and eastern iowa specimens were identified morphologic ...	2009	19960671
[prospects for treating mosquito-borne flavivirus encephalitides].	the japanese encephalitis virus and west nile virus belong to the family flaviviridae, genus flavivirus; they have a similar transmission cycle, with birds serving as the natural vertebrate host and mosquitoes, primarily, culex species, both serving as the enzootic vectors and infecting humans. these arboviruses have caused more human cases of severe neuroinvasive disease worldwide during the past decade than other mosquito-borne flaviviruses. the current data and concepts on the clinical manife ...	2009	20141019
structural modeling of the ns 3 helicase of tick-borne encephalitis virus and their virtual screening of potent drugs using molecular docking.	homology modeling of ns3 helicase in tick-borne encephalitis virus using known protein crystal structure was done. its 3-d structure was evaluated and validated using procheck comprising amino acid residues in favored region of ramachandran plot. helicase forms a large family of proteins which ubiquitously distributes in wide variety of organisms. it plays crucial role in transcription and replication of single-stranded viral rna genomes. consequently, ns3 represents an interesting target for th ...	2009	20640834
first human case of usutu virus neuroinvasive infection, italy, august-september 2009.	we report the first worldwide case of usutu virus (usuv) neuroinvasive infection in a patient with diffuse large b cell lymphoma who presented with fever and neurological symptoms and was diagnosed with meningoencephalitits. the cerebrospinal fluid was positive for usuv, and usuv was also demonstrated in serum and plasma samples by rt-pcr and sequencing. partial sequences of the premembrane and ns5 regions of the viral genome were similar to the usuv vienna and budapest isolates.	2009	20070936
the ifitm proteins mediate cellular resistance to influenza a h1n1 virus, west nile virus, and dengue virus.	influenza viruses exploit host cell machinery to replicate, resulting in epidemics of respiratory illness. in turn, the host expresses antiviral restriction factors to defend against infection. to find host cell modifiers of influenza a h1n1 viral infection, we used a functional genomic screen and identified over 120 influenza a virus-dependency factors with roles in endosomal acidification, vesicular trafficking, mitochondrial metabolism, and rna splicing. we discovered that the interferon-indu ...	2009	20064371
isolation and distribution of west nile virus in embryonated chicken eggs.	west nile virus (wnv) was identified from domestic psittacine birds by inoculating embryonated chicken eggs. most of the embryos died 5 days postinoculation; flavivirus was detected in some by negative-staining electron microscopy. immunohistochemistry performed on the embryos and their supporting structures detected the wnv antigen mainly in the chorioallantoic membrane, regardless of the inoculation route or passage number. wnv antigen was also found in the embryonic muscle (both skeletal and ...	2009	20095164
development of a vaccine to prevent japanese encephalitis: a brief review.	japanese encephalitis (icd 10: a83.0) is an important specific viral encephalitis caused by the japanese encephalitis virus, a virus of the flavivirus group. millions of people, especially those in endemic areas of developing countries in asia, are at high risk from this infection. therefore proper management to deal with this virus is essential. there is no specific treatment for japanese encephalitis virus. supportive and symptomatic treatments are usually used, which emphasize the importance ...	2009	20360904
high throughput prediction and analysis of small interfering rna from the 5'utr and capsid genes of flavivirus through in silico strategies.	the genus flavivirus in the family flaviviridae consists of many arthropod transmitted human pathogens. sirna is a novel strategy used for controlling the gene expression of flavivirus. these are 20-25 nucleotide long dsrna molecules that target genes at expression level. nine flavivirus genomes were used to in silico identify the sirna. twenty three sirnas were identified in the 5' utr and capsid protein encoding gene from flavivirus. these sirna can be useful to knockdown the flavivirus and it ...	2009	20640808
probing the mechanism of ph-induced large-scale conformational changes in dengue virus envelope protein using atomistic simulations.	one of the key steps in the infection of the cell by dengue virus is a ph-induced conformational change of the viral envelope proteins. these envelope proteins undergo a rearrangement from a dimer to a trimer, with large conformational changes in the monomeric unit. in this article, metadynamics simulations were used to enable us to understand the mechanism of these large-scale changes in the monomer. by using all-atom, explicit solvent simulations of the monomers, the stability of the protein s ...	2010	20643078
mouse stat2 restricts early dengue virus replication.	dengue virus encodes several interferon antagonists. among these the ns5 protein binds stat2, a necessary component of the type i interferon signaling pathway, and targets it for degradation. we now demonstrate that the ability of dengue ns5 to associate with and degrade stat2 is species specific. thus, ns5 is able to bind and degrade human stat2, but not mouse stat2. this difference was exploited to demonstrate, absent manipulation of the viral genome, that ns5-mediated ifn antagonism is essent ...	2010	21075352
human monoclonal antibodies to west nile virus identify epitopes on the prm protein.	hybridoma cell lines (2e8, 8g8 and 5g12) producing fully human monoclonal antibodies (hmabs) specific for the pre-membrane (prm) protein of west nile virus (wnv) were prepared using a human fusion partner cell line, mfp-2, and human peripheral blood lymphocytes from a blood donor diagnosed with wnv fever in 2004. using site-directed mutagenesis of a wnv-like particle (vlp) we identified 4 amino acid residues in the prm protein unique to wnv and important in the binding of these hmabs to the vlp. ...	2010	21084104
high affinity human antibody fragments to dengue virus non-structural protein 3.	the enzyme activities catalysed by flavivirus non-structural protein 3 (ns3) are essential for virus replication. they are distributed between the n-terminal protease domain in the first one-third and the c-terminal atpase/helicase and nucleoside 5' triphosphatase domain which forms the remainder of the 618-aa long protein.	2010	21085466
arbovirus detection in insect vectors by rapid, high-throughput pyrosequencing.	despite the global threat caused by arthropod-borne viruses, there is not an efficient method for screening vector populations to detect novel viral sequences. current viral detection and surveillance methods based on culture can be costly and time consuming and are predicated on prior knowledge of the etiologic agent, as they rely on specific oligonucleotide primers or antibodies. therefore, these techniques may be unsuitable for situations when the causative agent of an outbreak is unknown.	2010	21085471
japanese encephalitis virus remains an important cause of encephalitis in thailand.	japanese encephalitis virus (jev) is endemic in thailand and prevention strategies include vaccination, vector control, and health education.	2010	20674433
concurrent dengue and malaria in the amazon region.	the amazon region has extensive forested areas and natural ecosystems, providing favorable conditions for the existence of innumerous arboviruses. over 200 arboviruses have been isolated in brazil and about 40 are associated with human disease. four out of 40 are considered to be of public health importance in brazil: dengue viruses (1-4), oropouche, mayaro and yellow fever. along with these viruses, about 98% of the malaria cases are restricted to the legal amazon region.	2010	21085859
evolution of dengue virus type 3 genotype iii in venezuela: diversification, rates and population dynamics.	dengue virus (denv) is a member of the genus flavivirus of the family flaviviridae. denv are comprised of four distinct serotypes (denv-1 through denv-4) and each serotype can be divided in different genotypes. currently, there is a dramatic emergence of denv-3 genotype iii in latin america. nevertheless, we still have an incomplete understanding of the evolutionary forces underlying the evolution of this genotype in this region of the world. in order to gain insight into the degree of genetic v ...	2010	21087501
comparison of dengue virus type 2-specific small rnas from rna interference-competent and -incompetent mosquito cells.	the exogenous rna interference (rnai) pathway is an important antiviral defense against arboviruses in mosquitoes, and virus-specific small interfering (si)rnas are key components of this pathway. understanding the biogenesis of sirnas in mosquitoes could have important ramifications in using rnai to control arbovirus transmission. using deep sequencing technology, we characterized dengue virus type 2 (denv2)-specific small rnas produced during infection of aedes aegypti mosquitoes and a. aegypt ...	2010	21049014
minocycline differentially modulates viral infection and persistence in an experimental model of japanese encephalitis.	japanese encephalitis (je) is caused by a neurotropic flavivirus that causes cns damage that leads to death in acute cases or permanent neuropsychiatric sequel in survivors. the course of infection of this virus is not well defined though it is clear that it evades the host's innate immune response in the periphery. the current study was designed to investigate the time-dependent changes in the spleen and lymph node, apart from the cns that are infected by the japanese encephalitis virus (jev). ...	2010	20635157
the flvr-encoded murine oligoadenylate synthetase 1b (oas1b) suppresses 2-5a synthesis in intact cells.	resistance to flavivirus-induced disease in mice is conferred by the autosomal gene flv, identified as 2'-5' oligoadenylate synthetase 1b (oas1b). resistant mice express a full-length oas1b protein while susceptible mice express the truncated oas1btr. in this study, oas1b was shown to be an inactive synthetase. although the oas/rnase l pathway was previously shown to have an antiviral role during flavivirus infections, oas1b protein inhibited oas1a in vitro synthetase activity in a dose-dependen ...	2010	21056894
arboviral diseases and malaria in australia, 2008-09: annual report of the national arbovirus and malaria advisory committee.	the national notifiable diseases surveillance system received 8,677 notifications of diseases transmitted by mosquitoes in australia from 1 july 2008 to 30 june 2009. the alphaviruses, barmah forest and ross river, accounted for 6,574 (78%) of these notifications during 2008-09. there were 1,009 notifications of dengue virus infection locally-acquired in north queensland and 484 notified cases resulted from overseas travel. notification rates of dengue virus infection for 2008-09, regardless of ...	2010	21090179
advances in flavivirus vaccine development.	flaviviruses comprise a diverse family of viruses that are cumulatively responsible for hundreds of millions of cases of infection annually. the flavivirus genus includes both insect-vectored viruses, such as yellow fever and dengue, and non-vectored viruses such as hcv; the viruses have a broad range of disease presentation and geographic distribution. no specific antiviral therapies are currently available for the diseases caused by insect-vectored flaviviruses. thus, efforts have been focused ...	2010	21154147
[investigation of dengue virus and yellow fever virus seropositivities in blood donors from central/northern anatolia, turkey.]	dengue virus (denv) and yellow fever virus (yfv) are two of the globally prevalent vector-borne flaviviruses. data on these viruses from turkey is limited to a single study originating from the western, aegean region of turkey, where evidence for denv exposure had been confirmed in residents and presence of hemagglutination inhibiting antibodies against yfv had been revealed. the aim of this study was to investigate the rates of seropositivity of denv and yfv in blood donors from central/norther ...	2010	21063991
evaluation of a prototype dengue-1 dna vaccine in a phase 1 clinical trial.	candidate dengue dna vaccine constructs for each dengue serotype were developed by incorporating pre-membrane and envelope genes into a plasmid vector. a phase 1 clinical trial was performed using the dengue virus serotype-1 (denv-1) vaccine construct (d1me(100)). the study was an open-label, dose-escalation, safety and immunogenicity trial involving 22 healthy flavivirus-naïve adults assigned to one of two groups. each group received three intramuscular injections (0, 1, and 5 months) of either ...	2010	21111785
[investigation of west nile virus seroprevalence in healthy blood donors.]	west nile virus (wnv) which is a flavivirus transmitted by mosquitos, may lead to asymptomatic infection, mild febrile illness or encephalitis. many sporadic cases and major outbreaks of west nile fever have been reported worldwide, however, wnv infections have not been well documented in turkey. the aim of the present study was to determine the prevalence of past wnv infections in a population of blood donors. blood samples were collected from donors with their informed consent. samples were pr ...	2010	21063992
acute dengue myositis with rhabdomyolysis and acute renal failure.	dengue is an acute mosquito-borne infection caused by dengue viruses from the genus flavivirus. neurologic complications have been attributed chiefly to metabolic alterations and to focal and sometimes massive intracranial haemorrhages, but anecdotal cases and limited case series have indicated the possibility of viral cns and skeletal muscle invasion causing encephalitis and myositis. we present a case of a 40-year-old male who presented with severe dengue myositis resulting in quadriparesis, r ...	2010	21085538
prediction of the post-translational modification sites on dengue virus e protein and deciphering their role in pathogenesis.	dengue virus, a member of the flavivirus family, is a mosquito-borne viral pathogen for which any specific treatment or control of infection by vaccination is yet to be conclusive. the envelope glycoprotein, e, mediates viral entry by membrane fusion. elucidation of post-translational modification sites in e protein followed by sequence alignment produced stretches of residues which are conserved in most of the members of flaviviruses. presence of protein kinase a (pka) and protein kinase g (pkg ...	2010	21224207
insertion of microrna targets into the flavivirus genome alters its highly neurovirulent phenotype.	flaviviruses such as west nile, japanese encephalitis, and tick-borne encephalitis (tbev) viruses are important neurotropic human pathogens, causing a devastating and often fatal neuroinfection. here, we demonstrate that incorporation into the viral genome of a target sequence for cellular micrornas expressed in the central nervous system (cns) enables alteration of the neurovirulence of the virus and control of the neuropathogenesis of flavivirus infection. as a model virus for this type of mod ...	2010	21123372
the 5' and 3' downstream aug region elements are required for mosquito-borne flavivirus rna replication.	flaviviruses require complementarity between the 5' and 3' ends of the genome for rna replication. for mosquito-borne flaviviruses, the cyclization sequences (cs) and upstream of aug region (uar) elements at the genomic termini are necessary for viral rna replication, and a third motif, the downstream of aug region (dar), was recently designated for dengue virus. the 3' dar sequence is also part of a hairpin (hp-3'sl), and both complementarity between 5' and 3' dar motifs and formation of the hp ...	2010	21123391
[sero-epidemiological study of west nile virus circulation in human in tunisia.]	west nile virus (wnv) is an arbovirus classified into the family of flaviviridae, genus flavivirus. it is responsible for neurological diseases that occurred frequently as outbreaks and considered as an emerging infection in different regions of the world. in tunisia, two outbreaks of meningoencephalitis due to this virus occurred, in 1997 and 2003. the virus circulation is studied only in sahel, region affected by the two epidemics. the aim of this study is to determine if wnv is present in oth ...	2010	21161623
antiviral and neuroprotective role of octaguanidinium dendrimer-conjugated morpholino oligomers in japanese encephalitis.	japanese encephalitis (je), caused by a mosquito-borne flavivirus, is endemic to the entire south-east asian and adjoining regions. currently no therapeutic interventions are available for je, thereby making it one of the most dreaded encephalitides in the world. an effective way to counter the virus would be to inhibit viral replication by using anti-sense molecules directed against the viral genome. octaguanidinium dendrimer-conjugated morpholino (or vivo-morpholino) are uncharged anti-sense o ...	2010	21124882
identification and characterization of a virus-specific continuous b-cell epitope on the prm/m protein of japanese encephalitis virus: potential application in the detection of antibodies to distinguish japanese encephalitis virus infection from west nile virus and dengue virus infections.	differential diagnose of japanese encephalitis virus (jev) infection from other flavivirus especially west nile virus (wnv) and dengue virus (dv) infection was greatly hindered for the serological cross-reactive. virus specific epitopes could benefit for developing jev specific antibodies detection methods. to identify the jev specific epitopes, we fully mapped and characterized the continuous b-cell epitope of the prm/m protein of jev.	2010	20858291
development of sanofi pasteur tetravalent dengue vaccine.	the sanofi pasteur tetravalent dengue vaccine candidate is composed of 4 recombinant live attenuated vaccines based on a yellow fever vaccine 17d (yfv 17d) backbone, each expressing the prm and envelope genes of one of the four dengue virus serotypes. pre-clinical studies have demonstrated that the tv dengue vaccine is genetically and phenotypically stable, non-hepatotropic, less neurovirulent than yfv 17d and does not infect mosquitoes by the oral route. in vitro and in vivo preclinical studies ...	2010	20861669
evaluation of core and ns4b synthetic peptide-based immunoassays for the detection of hepatitis c virus antibodies in clinical samples from cameroon, central africa.	according to previous data, the antibodies produced during natural hepatitis c virus (hcv) infection frequently recognize amino acids 10-43 in the core protein and 1689-1740 or 1921-1940 in the non-structural 4b (ns4b) protein. the reactivity of these peptides with the corresponding antibodies has mainly been evaluated using serum samples from western countries where hcv genotype 1 (hcv-1) is predominant, and no information is available concerning samples from sub-saharan countries where high hc ...	2010	20621554
molecular mechanisms involved in the early steps of flavivirus cell entry.	flaviviruses enter their host cells by receptor-mediated endocytosis, a well-orchestrated process of receptor recognition, penetration and uncoating. recent findings on these early steps in the life cycle of flaviviruses are the focus of this review.	2010	20869460
peptide inhibitors of flavivirus entry derived from the e protein stem.	peptides derived from the "stem" of dengue virus (dv) type 2 (dv2) envelope (e) protein inhibit dv2 infectivity, targeting a late-stage fusion intermediate. we show here that stem peptides from all dv serotypes cross-inhibit dv1 to dv4 but that corresponding peptides derived from related flaviviruses do not. this failure to inhibit infection is not due to poor interaction with the e protein but rather to loss of association with the virion membrane. residues 442 to 444 of the stem are determinan ...	2010	20881042
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 ...	2010	20510927
alkhumra (alkhurma) virus outbreak in najran, saudi arabia: epidemiological, clinical, and laboratory characteristics.	after its first appearance in alkhumra district of jeddah in 1994-1995, and then in makkah in 2001-2003, the new hemorrhagic fever virus, known as alkhumra (misnamed as alkhurma) virus (alkv), has subsequently been reported from najran, in the south border of saudi arabia.	2010	20920527
[examination of mosquitoes collected in southern moravia in 2006-2008 tested for arboviruses].	the main goals of the study were to carry out virus isolation attempts on vero cell cultures from mosquitoes collected in southern moravia (breclav district, czech republic) and to identify the isolates using a microtiter virus neutralization test. a total of 9.742 female mosquitoes belonging to 13 species were examined, and three viral strains were isolated, all from the mosquitoes collected in 2006: two of these isolates were identified as tahyna orthobunyavirus (both obtained from aedes vexan ...	2010	20925246
amphipathic alpha-helix ah2 is a major determinant for the oligomerization of hepatitis c virus nonstructural protein 4b.	nonstructural protein 4b (ns4b) is a key organizer of hepatitis c virus (hcv) replication complex formation. it induces a specific membrane rearrangement, designated membranous web, that serves as a scaffold for the hcv replication complex. however, the mechanisms underlying membranous web formation are poorly understood. based on fluorescence resonance energy transfer (fret) and confirmatory coimmunoprecipitation analyses, we provide evidence for an oligomerization of ns4b in the membrane envir ...	2010	20926561
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 ...	2010	20522297
[japanese encephalitis virus and other flaviviruses].		2010	20942080
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 ...	2010	20551474
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 ...	2010	20576021
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 ...	2010	20579348
genetic analysis of west nile virus containing a complete 3'csi rna deletion.	we report a genetic interplay among three pairs of long-distance rna interactions that are involved in west nile virus (wnv) genome cyclization and replication: 5'cs/3'csi (conserved sequence), 5'uar/3'uar (upstream aug region), and 5'dar/3'dar (downstream aug region). deletion of the complete 3'csi element is lethal for wnv replication, but the replication of the 3'csi deletion virus could be rescued by second site mutations. functional analysis, using a genome-length rna and replicon, mapped t ...	2010	20965539
prevalence of neutralizing antibodies to west nile virus in eleonora's falcons in the canary islands.	birds are the major amplifying host for west nile virus (wnv), a flavivirus that may affect humans and transmitted by bloodsucking vectors. eleonora's falcons (falco eleonorae) migrate to the canary islands annually from wnv-endemic regions. to investigate the possible role of eleonora's falcons in the circulation of wnv, we measured wnv-specific antibodies in 81 falcons captured in 2006. none of the nestlings but 14.8% of the adults had wnv-neutralizing antibodies. rt-pcr did not detect flavivi ...	2010	20966288
in vitro and in vivo studies identify important features of dengue virus pr-e protein interactions.	flaviviruses bud into the endoplasmic reticulum and are transported through the secretory pathway, where the mildly acidic environment triggers particle rearrangement and allows furin processing of the prm protein to pr and m. the peripheral pr peptide remains bound to virus at low ph and inhibits virus-membrane interaction. upon exocytosis, the release of pr at neutral ph completes virus maturation to an infectious particle. together this evidence suggests that pr may shield the flavivirus fusi ...	2010	20975939
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.	2010	20592138
the live-attenuated yellow fever vaccine 17d induces broad and potent t cell responses against several viral proteins in indian rhesus macaques--implications for recombinant vaccine design.	the yellow fever vaccine 17d (yf17d) is one of the most effective vaccines. its wide use and favorable safety profile make it a prime candidate for recombinant vaccines. it is believed that neutralizing antibodies account for a large measure of the protection afforded to yf17d-vaccinated individuals, however cytotoxic t lymphocyte (ctl) responses have been described in the setting of yf17d vaccination. yf17d is an ssrna flavivirus that is translated as a full-length polyprotein, several domains ...	2010	20607226
antiviral activities of isg20 in positive-strand rna virus infections.	isg20 is an interferon-inducible 3'-5' exonuclease that inhibits replication of several human and animal rna viruses. however, the specificities of isg20's antiviral action remain poorly defined. here we determine the impact of ectopic expression of isg20 on replication of several positive-strand rna viruses from distinct viral families. isg20 inhibited infections by cell culture-derived hepatitis c virus (hcv) and a pestivirus, bovine viral diarrhea virus and a picornavirus, hepatitis a virus. ...	2010	21036379
serological investigations of flavivirus prevalence in khammouane province, lao people's democratic republic, 2007-2008.	a large-scale cross-sectional seroprevalence study of dengue (den) and japanese encephalitis (je) was conducted in khammouane province, lao pdr, as part of the initial baseline health impact assessment of the nam theun 2 hydroelectric dam construction project. health surveys were performed between may 2007 and february 2008 with serum samples collected from healthy individuals involved in the resettlement program of 16 villages (total surveyed population 4,369). hemagglutination inhibition assay ...	2010	21036856
development of a highly sensitive real-time rt-pcr protocol for the detection of classical swine fever virus independent of the 5' untranslated region.	classical swine fever (csf) is one of the most severe diseases of pigs, and can cause immense economic losses. real-time reverse transcription polymerase chain reaction (rrt-pcr) can be used as a sensitive and specific method for detection of classical swine fever virus (csfv). different published protocols are used routinely for csfv diagnosis. however, almost all these systems use the highly conserved 5' untranslated region (5'utr) of the csfv genome as template. for a reliable diagnosis in ou ...	2010	21111760
structural and functional analyses of a conserved hydrophobic pocket of flavivirus methyltransferase.	the flavivirus methyltransferase (mtase) sequentially methylates the n7 and 2'-o positions of the viral rna cap (gpppa-rna → m(7)gpppa-rna → m(7)gpppam-rna), using s-adenosyl-l-methionine (adomet) as a methyl donor. we report here that sinefungin (sin), an adomet analog, inhibits several flaviviruses through suppression of viral mtase. the crystal structure of west nile virus mtase in complex with sin inhibitor at 2.0-å resolution revealed a flavivirus-conserved hydrophobic pocket located next t ...	2010	20685660
molecular epidemiology of powassan virus in north america.	powassan virus (pow) is a tick-borne flavivirus distributed in canada, the northern usa and the primorsky region of russia. pow is the only tick-borne flavivirus endemic to the western hemisphere, where it is transmitted mainly between ixodes cookei and groundhogs (marmota monax). deer tick virus (dtv), a genotype of pow that has been frequently isolated from deer ticks (ixodes scapularis), appears to be maintained in an enzootic cycle between these ticks and white-footed mice (peromyscus leucop ...	2010	20631087
alkhurma hemorrhagic fever in humans, najran, saudi arabia.	alkhurma virus is a flavivirus, discovered in 1994 in a person who died of hemorrhagic fever after slaughtering a sheep from the city of alkhurma, saudi arabia. since then, several cases of alkhurma hemorrhagic fever (alkhf), with fatality rates up to 25%, have been documented. from january 1, 2006, through april 1, 2009, active disease surveillance and serologic testing of household contacts identified alkhf in 28 persons in najran, saudi arabia. for epidemiologic comparison, serologic testing ...	2010	21122217
alkhurma hemorrhagic fever in travelers returning from egypt, 2010.	two travelers returning to italy from southern egypt were hospitalized with a fever of unknown origin. test results showed infection with alkhurma virus. the geographic distribution of this virus could be broader than previously thought.	2010	21122237
rna structures required for production of subgenomic flavivirus rna.	flaviviruses are a group of single-stranded, positive-sense rna viruses causing ∼100 million infections per year. we have recently shown that flaviviruses produce a unique, small, noncoding rna (∼0.5 kb) derived from the 3' untranslated region (utr) of the genomic rna (grna), which is required for flavivirus-induced cytopathicity and pathogenicity (g. p. pijlman et al., cell host microbe, 4: 579-591, 2008). this rna (subgenomic flavivirus rna [sfrna]) is a product of incomplete degradation of gr ...	2010	20719943
construction of a dengue virus type 4 reporter replicon and analysis of temperature-sensitive mutations in non-structural proteins 3 and 5.	replicon systems have been useful to study mechanisms of translation and replication of flavivirus rnas. in this study, we constructed a dengue virus 4 replicon encoding a renilla luciferase (r(luc)) reporter, and six single-residue substitution mutants were generated: l128f and s158p in the non-structural protein (ns) 3 protease domain gene, and n96i, n390a, k437r and m805i in the ns5 gene. the effects of these substitutions on viral rna translation and/or replication were examined by measuring ...	2010	20631089
critical role of lipid rafts in virus entry and activation of phosphoinositide 3' kinase/akt signaling during early stages of japanese encephalitis virus infection in neural stem/progenitor cells.	japanese encephalitis virus (jev), the leading cause of acute encephalitis in south-east asia is a neurotropic virus infecting various cns cell types. most flaviviruses including jev get internalised into cells by receptor-mediated endocytosis, which involve clathrin and membrane cholesterol. the cholesterol-enriched membrane microdomains referred to as lipid rafts act as portals for virus entry in a number of enveloped viruses, including flavivirus. however, the precise role played by membrane ...	2010	20722967
west nile virus--neutralizing antibodies in humans in greece.	serum samples collected during march-may 2007 from 392 residents of imathia prefecture, northern greece, were tested by indirect immunofluorescence assay and enzyme-linked immunosorbent assay for igg antibodies against west nile virus (wnv). microneutralization assay was applied in six positive samples. four (4/392, 1.02%) were found positive for wnv-neutralizing antibodies. none of the positive individuals had a history of travel in endemic area or flavivirus vaccination, suggesting that wnv, o ...	2010	20738157
alkylated porphyrins have broad antiviral activity against hepadnaviruses, flaviviruses, filoviruses, and arenaviruses.	we screened ∼2,200 compounds known to be safe in people for the ability to reduce the amount of virion-associated hepatitis b virus (hbv) dna in the culture medium of producer cells. these efforts led to the discovery of an alkylated porphyrin, chlorophyllide, as the compound that achieved the greatest reduction in signal. here we report that chlorophyllide directly and quantitatively disrupted hbv virions at micromolar concentrations, resulting in the loss of all detectable virion dna, without ...	2010	21135183
biochemical characterisation of murray valley encephalitis virus proteinase.	murray valley encephalitis virus (mvev) is a member of the flavivirus group, a large family of single stranded rna viruses, which cause serious disease in all regions of the world. its genome encodes a large polyprotein which is processed by both host proteinases and a virally encoded serine proteinase, non-structural protein 3 (ns3). ns3, an essential viral enzyme, requires another virally encoded protein cofactor, ns2b, for proteolytic activity. the cloning, expression and biochemical characte ...	2010	20621842
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 ...	2010	20600950
west nile virus monitoring of migratory and resident birds in germany.	west nile virus (wnv) is a mosquito-borne flavivirus naturally circulating in wild bird populations. the virus is also capable to infect a broad range of vertebrate species. humans and equines are highly susceptible and can develop mild flu-like illnesses as well as severe encephalitis leading to fatalities. most recently, wnv was found to circulate in countries close to germany, such as france, czech republic, italy, austria, and hungary. given this epidemiological situation its spread to germa ...	2010	20854016
hsp110-mediated enhancement of cd4+ t cell responses to the envelope glycoprotein of members of the family flaviviridae in vitro does not occur in vivo.	the use of heat shock proteins (hsp) to enhance activation of the immune response to chaperoned antigen is being explored for immunotherapy. hsp110 chaperones large protein substrates more effectively than hsp70, offering the potential to use complex antigens containing multiple epitopes in hsp-based vaccines. in this study, we investigated the ability of recombinant bovine hsp110 to chaperone e2 glycoprotein, the major envelope protein of bovine viral diarrhea virus (bvdv) and the dominant targ ...	2010	21147937
restoration of replication-defective dengue type 1 virus bearing mutations in the n-terminal cytoplasmic portion of ns4a by additional mutations in ns4b.	flavivirus ns4a has an n-terminal hydrophilic cytoplasmic portion; however, the role of this portion remains poorly understood. in this study, we show that a recombinant dengue type 1 virus (denv-1) in which a subportion (amino acids 27-34) of the n-terminal portion of ns4a is replaced by the corresponding region from japanese encephalitis virus (jev) is defective in replication. using the defective mutant clone ns4a(27-34(jev)), we recovered suppressor mutant viruses that carry various non-syno ...	2010	20882304
a rapid and specific real-time rt-pcr assay to identify usutu virus in human plasma, serum, and cerebrospinal fluid.	usutu virus (usuv), a flavivirus that belongs to the japanese encephalitis virus (jev) family, has recently emerged as a human pathogen, necessitating new diagnostic tools.	2010	21156352
molecular phylogeny of edge hill virus supports its position in the yellow fever virus group and identifies a new genetic variant.	edge hill virus (ehv) is a mosquito-borne flavivirus isolated throughout australia during mosquito surveillance programs. while not posing an immediate threat to the human population, ehv is a taxonomically interesting flavivirus since it remains the only member of the yellow fever virus (yfv) sub-group to be detected within australia. here we present both an antigenic and genetic investigation of collected isolates, and confirm taxonomic classification of the virus within the yfv-group. isolate ...	2010	20938485
network based analysis of hepatitis c virus core and ns4b protein interactions.	hepatitis c virus (hcv) is a major cause of chronic liver disease worldwide. here we attempt to further our understanding of the biological context of protein interactions in hcv pathogenesis, by investigating interactions between hcv proteins core and ns4b and human host proteins. using the yeast two-hybrid (y2h) membrane protein system, eleven human host proteins interacting with core and 45 interacting with ns4b were identified, most of which are novel. these interactions were used to infer o ...	2010	20953506
development of human-murine chimeric immunoglobulin g for use in the serological detection of human flavivirus and alphavirus antibodies.	diagnosis of human arboviral infections relies heavily on serological techniques such as the immunoglobulin m (igm) antibody capture enzyme-linked immunosorbent assay (mac-elisa) and the indirect igg elisa. broad application of these assays is hindered by the lack of standardized positive human control sera that react with a wide variety of flaviviruses (e.g., dengue, west nile, yellow fever, japanese encephalitis, saint louis encephalitis, and powassan viruses), or alphaviruses (e.g., eastern e ...	2010	20739503
new insights into structure and replication of the hepatitis c virus and clinical implications.	with the advent of efficient systems to propagate the hepatitis c virus (hcv) in cultured cells important new discoveries have been made. for instance, several molecules required for hcv infection of hepatocytes have been identified and first insights into the entry pathway have been gained. ribonucleic acid (rna) replication and virion assembly were found to be tightly linked to lipid metabolism and numerous host factors contributing to viral replication have been identified. some of them such ...	2010	20960374
evidence of simultaneous circulation of west nile and usutu viruses in mosquitoes sampled in emilia-romagna region (italy) in 2009.	in recent years human diseases due to mosquito-borne viruses were increasingly reported in emilia-romagna region (italy), from the chikungunya virus in 2007 to the west nile virus (wnv) in 2008. an extensive entomological survey was performed in 2009 to establish the presence and distribution of mosquito arboviruses in this region, with particular reference to flaviviruses.	2010	21179462
emergence and establishment of usutu virus infection in wild and captive avian species in and around zurich, switzerland--genomic and pathologic comparison to other central european outbreaks.	in late summer 2006 considerable mortality in wild and captive passeriformes and strigiformes was observed in zurich, switzerland. all animals were found in a range of 2 km(2). observed clinical signs involved depression, ruffled plumage, incoordination, seizures and peracute death. nutritional status was generally moderate to poor in wild birds, and variable in captive animals. necropsy showed marked splenomegaly, a mild hepatomegaly, and pulmonary hyperemia in most animals. histopathologic les ...	2010	20980109
anthracene-based inhibitors of dengue virus ns2b-ns3 protease.	dengue virus (denv) is a mosquito-borne flavivirus that has strained global healthcare systems throughout tropical and subtropical regions of the world. in addition to plaguing developing nations, it has re-emerged in several developed countries with recent outbreaks in the usa (cdc, 2010), australia (hanna et al., 2009), taiwan (kuan et al., 2010) and france (la ruche et al., 2010). denv infection can cause significant disease, including dengue fever, dengue hemorrhagic fever, dengue shock synd ...	2010	21185332
predictive diagnostic value of the tourniquet test for the diagnosis of dengue infection in adults.	to examine the accuracy of the admission tourniquet test in the diagnosis of dengue infection among lao adults.	2010	20958892
west nile virus differentially modulates the unfolded protein response to facilitate replication and immune evasion.	for intracellular survival it is imperative that viruses have the capacity to manipulate various cellular responses, including metabolic and biosynthetic pathways. the unfolded protein response (upr) is induced by various external and internal stimuli, including the accumulation of misfolded proteins in the endoplasmic reticulum (er). our previous studies have indicated that the replication and assembly of the flavivirus west nile virus strain kunjin virus (wnv(kun)) is intimately associated wit ...	2010	21191014
appraising the roles of cbll1 and the ubiquitin/proteasome system for flavivirus entry and replication.	the ubiquitin ligase cbll1 (also known as hakai) has been proposed to be a critical cellular factor exploited by west nile virus (wnv) for productive infection. cbll1 has emerged as a major hit in a recent rna interference screen designed to identify cellular factors required for the early stages of the wnv life cycle. follow-up experiments showed that hela cells knocked down for cbll1 by a small interfering rna (sirna) failed to internalize wnv particles and resisted infection. furthermore, dep ...	2010	21191016
cross-genotypic polyclonal anti-hcv antibodies from human ascitic fluid.	many anti-hcv antibodies are available, but more are needed for research and clinical applications. this study examines whether ascitic fluid from cirrhotic patients could be a source of reagent-grade antibodies. ascitic fluid from 29 hcv patients was screened by elisa for anti-hcv antibodies against three viral proteins: core, ns4b, and ns5a. significant patient-to-patient variability in anti-hcv antibody titers was observed. total ascitic fluid igg purified by protein-a chromatography reacted ...	2010	21034775
virtual ligand screening of the national cancer institute (nci) compound library leads to the allosteric inhibitory scaffolds of the west nile virus ns3 proteinase.	viruses of the genus flavivirus are responsible for significant human disease and mortality. the n-terminal domain of the flaviviral nonstructural (ns)3 protein codes for the serine, chymotrypsin-fold proteinase (ns3pro). the presence of the nonstructural (ns)2b cofactor, which is encoded by the upstream gene in the flaviviral genome, is necessary for ns3pro to exhibit its proteolytic activity. the two-component ns2b-ns3pro functional activity is essential for the viral polyprotein processing an ...	2010	21050032
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; ...	2010	20536361
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 ...	2010	20538092
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 ...	2010	20538858
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 ...	2010	20540055