Publications

TitleAbstractYear
Filter
PMID(sorted ascending)
Filter
[saint louis encephalitis virus in buenos aires city during the outbreak of dengue in 2009.]we report the case of a male, 80-year-old resident in the city of buenos aires, with a diagnosis of st. louis encephalitis (sle) during a countrywide dengue outbreak, from january to may 2009. the patient had a chronic lymphocytic leukemia treated with chlorambucil, prostate cancer (hormone therapy and radiotherapy) and images consistent with bone metastases. cerebrospinal fluid examination showed pleocytosis with a predominance of mononuclear cells and high protein concentration. bacteria, fung ...201121745774
a case of aseptic meningitis due to japanese encephalitis virus in a traveller returning from the philippines.we here report the case of japanese encephalitis virus (jev) meningitis in a previously healthy young women returning from a trip to the philippines. jev is a mosquito-borne encephalitic flavivirus pathogen, which is endemic in south east and eastern asia. our patient presented with aseptic meningitis and recovered well under supportive therapy. although the chance of a traveller getting symptomatic jev infection is extremely low, clinicians and microbiologist should be aware of patients contrac ...201121748935
west nile virus infection in the united states: overview as a public health issue.in august 1999, west nile virus (wnv), a mosquito-transmitted flavivirus, appeared in new york city. this represented the first time a major outbreak of this old world virus caused an epidemic in the western hemisphere. by december 2002, the outbreak had spread, probably via avian migratory flyways, to involve 44 states and the district of columbia. the future epidemiology of wnv infection in the united states will be difficult to forecast. in the absence of an effective human vaccine, the only ...200321765762
the interaction of flavivirus m protein with light chain tctex-1 of human dynein plays a role in late stages of virus replication.the role of the membrane protein (prm/m) in flavivirus life cycle remains unclear. here, we identified a cellular interactor to the 40-residue-long ectodomain of prm/m (ectom) using a yeast two-hybrid screen against a human cdna library and gst pull-down assays. we showed that dynein light chain tctex-1 interacts with the ectom of dengue 1-4, west nile, and japanese encephalitis flaviviruses. no interaction was found with yellow fever and tick-borne flaviviruses. this interaction is highly speci ...201121767858
serologic evidence of west nile virus in wild ducks captured in major inland resting sites for migratory waterfowl in south korea.the rapid global expansion of west nile virus (wnv) has recently raised concerns regarding its possible spread into south korea. to date, wnv infection in wild birds in south korea has not been identified. bird migration is thought to be involved in spreading wnv, and wild birds are the possible routes of introduction of wnv infection. to assess the risk of wnv infection in south korea, we conducted a nationwide wnv surveillance of wild birds, with an emphasis on migratory ducks from wnv-affecte ...201121767922
rna binding property and rna chaperone activity of dengue virus core protein and other viral rna-interacting proteins.in this study we showed that the dengue virus (denv) core protein forms a dimer with an a-helix-rich structure, binds rna and facilitates the strand annealing process. to assess the rna chaperone activity of this core protein and other dengue viral rna-interacting proteins, such as ns3 helicase and ns5 proteins, we engineered cis- and trans-cleavage hammerhead ribozyme constructs carrying denv genomic rna elements. our results indicate that denv core protein facilitates typical hammerhead struct ...201121771593
north american west nile viral genotype isolates demonstrate differential replicative capacity in response to temperature.west nile virus (wnv) was first documented in california during the summer of 2003, and the virus has subsequently become endemic throughout the state. sequence analysis has demonstrated that the circulating strains are representative of the north american (wn02) genotype that has displaced the invading east coast genotype (ny99). a recent study has indicated that enhanced vector competence at elevated temperatures may have played a role in the displacement of the east coast genotype by wn02. in ...201121775581
prevalence of antibodies to phleboviruses and flaviviruses in peja, kosovo.clin microbiol infect 2011; 17: 1180-1182 abstract: in order to investigate the current and past activity of phlebovirus and flavivirus in kosovo, a seroprevalence study among 200 blood donors was performed. positive results were obtained for the phleboviruses tosv and sfnv, and for a flavivirus of the japanese encephalitis group. no positive results for tbev were observed.201121781206
the pathogenesis of dengue.dengue is an important cause of childhood and adult morbidity in asian and latin american countries and its geographic footprint is growing. the clinical manifestations of dengue are the expression of a constellation of host and viral factors, some acquired, others intrinsic to the individual. the virulence of the virus plus the flavivirus infection history, age, gender and genotype of the host all appear to help shape the severity of infection. similarly, the characteristics of the innate and a ...201121781999
a high-throughput screening assay for the identification of flavivirus ns5 capping enzyme gtp-binding inhibitors: implications for antiviral drug development.there are no effective antivirals currently available for the treatment of flavivirus infection in humans. as such, the identification and characterization of novel drug target sites are critical to developing new classes of antiviral drugs. the flavivirus ns5 n-terminal capping enzyme (ce) is vital for the formation of the viral rna cap structure, which directs viral polyprotein translation and stabilizes the 5' end of the viral genome. the structure of the flavivirus ce has been solved, and a ...201121788392
enhancing the utility of a prm/e-expressing chimeric vaccine for japanese encephalitis by addition of the jev ns1 gene.recently, we demonstrated that a single-cycle west nile virus (wnv) named replivax wn could be used to produce a chimeric japanese encephalitis (je) vaccine (replivax je) by replacing the wnv prm/e genes with those of jev. here, we tested if replacement of wnv ns1 gene in replivax je with that of jev (producing triplivax je) could produce a superior vaccine. triplivax je elicited higher anti-e immunity and displayed better efficacy in mice than replivax je. furthermore, triplivax je displayed re ...201121798299
dengue virus infection in africa.reported incidence of dengue has increased worldwide in recent decades, but little is known about its incidence in africa. during 1960-2010, a total of 22 countries in africa reported sporadic cases or outbreaks of dengue; 12 other countries in africa reported dengue only in travelers. the presence of disease and high prevalence of antibody to dengue virus in limited serologic surveys suggest endemic dengue virus infection in all or many parts of africa. dengue is likely underrecognized and unde ...201121801609
bagaza virus in partridges and pheasants, spain, 2010.in september 2010, an unusually high number of wild birds (partridges and pheasants) died in cádiz in southwestern spain. reverse transcription pcr and virus isolation detected flavivirus infections. complete nucleotide sequence analysis identified bagaza virus, a flavivirus with a known distribution that includes sub-saharan africa and india, as the causative agent.201121801633
west nile virus aseptic meningitis and stuttering in woman.to the editor: west nile virus (wnv), a mosquito-borne flavivirus, is closely related to st. louis encephalitis virus and japanese encephalitis virus (jev). most cases of wnv have been mild, but neuroinvasive disease has been observed, especially among older persons and immunocompromised persons (1,2). the most common neurologic manifestations of wnv are aseptic meningitis, meningoencephalitis, and encephalitis with or without acute flaccid paralysis (3). other less common neurologic manifestati ...201121801656
novel formulations enhance the thermal stability of live-attenuated flavivirus vaccines.thermal stability is important for the manufacture, distribution and administration of vaccines, especially in tropical developing countries, where particularly adverse field conditions exist. current live-attenuated flavivirus vaccines exhibit relatively poor liquid stability in clinical settings, and clinicians are instructed to discard the yellow fever vaccine 1h after reconstitution. we have identified novel combinations of excipients that greatly enhance the thermal stability of live-attenu ...201121803103
maturation of dengue virus nonstructural protein 4b in monocytes enhances production of dengue hemorrhagic fever-associated chemokines and cytokines.high levels of viremia and chemokines and cytokines underlie the progression of severe dengue disease. dengue virus (denv) preferentially infects peripheral blood monocytes, which secrete elevated levels of immunomediators in patients with severe disease. further, denv nonstructural proteins (ns) are capable of modifying intracellular signaling, including interferon inhibition. we demonstrate that peak secretions of immunomediators such as il-6, il-8, ip-10, tnfa or ifn? in denv-infected monocyt ...201121810535
safety and immunogenicity of a tetravalent live-attenuated dengue vaccine in flavivirus-naive infants.abstract. a phase i/ii observer-blind, randomized, controlled trial evaluated the safety and immunogenicity of a dengue virus (denv) vaccine candidate in healthy thai infants (aged 12-15 months) without measurable pre-vaccination neutralizing antibodies to denv and japanese encephalitis virus. fifty-one subjects received two doses of either denv (n = 34; four received 1/10th dose) or control vaccine (n = 17; dose 1, live varicella; dose 2, haemophilus influenzae type b). after each vaccine dose, ...201121813857
an experimental model of meningoencephalomyelitis by rocio flavivirus in balb/c mice: inflammatory response, cytokine production, and histopathology.abstract. rocio virus (rocv) is a flavivirus, probably transmitted by culex mosquitoes and maintained in nature as a zoonosis of wild birds. rocio virus caused a human epidemic of severe encephalitis that lasted from 1973 to 1980 in the ribeira valley, in the southeastern coast of brazil. after this outbreak, serologic evidence of rocv circulation has been reported and public health authorities are concerned about a return of rocv outbreaks in brazil. we show here a study on the pathogenesis and ...201121813860
broad-spectrum antiviral therapeutics.currently there are relatively few antiviral therapeutics, and most which do exist are highly pathogen-specific or have other disadvantages. we have developed a new broad-spectrum antiviral approach, dubbed double-stranded rna (dsrna) activated caspase oligomerizer (draco) that selectively induces apoptosis in cells containing viral dsrna, rapidly killing infected cells without harming uninfected cells. we have created dracos and shown that they are nontoxic in 11 mammalian cell types and effect ...201121818340
dengue virus isolation relying on antibody-dependent enhancement mechanism using fc+¦r-expressing bhk cells and a monoclonal antibody with infection-enhancing capacity.background: virus isolation is the most reliable evidence of dengue virus (denv) infection. however, conventional virus isolation methods generally posses lower sensitivity and are time consuming as compared to other diagnostic methods such as detection of viral genome by rt-pcr, and determination of ns1 antigen and anti-denv antibody by elisa. objectives: a virus isolation method relying on the antibody-dependent enhancement mechanism was established and the assay's efficacy in denv isolation w ...201121824813
stability of yellow fever virus under recombinatory pressure as compared with chikungunya virus.recombination is a mechanism whereby positive sense single stranded rna viruses exchange segments of genetic information. recent phylogenetic analyses of naturally occurring recombinant flaviviruses have raised concerns regarding the potential for the emergence of virulent recombinants either post-vaccination or following co-infection with two distinct wild-type viruses. to characterize the conditions and sequences that favor rna arthropod-borne virus recombination we constructed yellow fever vi ...201121826243
a single dose of the denv-1 candidate vaccine rden1+ö30 is strongly immunogenic and induces resistance to a second dose in a randomized trial.dengue is an emerging infectious disease that has become the most important arboviral infection worldwide. there are four serotypes of dengue virus, denv-1, denv-2, denv-3, and denv-4, each capable of causing the full spectrum of disease. rden1+ö30 is a live attenuated investigational vaccine for the prevention of denv-1 illness and is also a component of an investigational tetravalent denv vaccine currently in phase i evaluation. a single subcutaneous dose of rden1+ö30 was previously shown to b ...201121829748
rab5 and class iii pi-3-kinase vps34 are involved in hepatitis c virus ns4b-induced autophagy.autophagy has been shown to facilitate replication or production of hepatitis c virus (hcv); nevertheless, how hcv induces autophagy remains unclear. here, we demonstrate that hcv nonstructural protein 4b (ns4b) alone can induce autophagy signaling; its amino acid residues 1-190 are sufficient for this induction. further studies showed that the phosphorylation levels of s6k and 4e-bp1 were not altered, suggesting that mtor/s6 kinase pathway and mtor/4ebp1 pathway did not contribute to ns4b- or h ...201121835792
mitochondrial-associated endoplasmic reticulum membranes (mam) form innate immune synapses and are targeted by hepatitis c virus.rig-i is a cytosolic pathogen recognition receptor that engages viral rna in infected cells to trigger innate immune defenses through its adaptor protein mavs. mavs resides on mitochondria and peroxisomes, but how its signaling is coordinated among these organelles has not been defined. here we show that a major site of mavs signaling is the mitochondrial-associated membrane (mam), a distinct membrane compartment that links the endoplasmic reticulum to mitochondria. during rna virus infection, r ...201121844353
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
host-feeding patterns of native culex pipiens and invasive aedes albopictus mosquitoes (diptera: culicidae) in urban zones from barcelona, spain.the feeding patterns of haematophagous arthropods are of major importance in the amplification and transmission of infectious disease agents to vertebrate hosts, including humans. the establishment of new vector populations in nonnative range might alter transmission networks. the asian tiger mosquito aedes albopictus (skuse) represents an example of how an invasive species can alter the risk of viral transmission to humans. blood meal molecular identification from two sympatric mosquito species ...201121845962
Assessing ubiquitination of viral proteins: Lessons from flavivirus NS5.Ubiquitin (Ub) conjugation to a substrate protein is a widely used cellular mechanism for control of protein stability and function, modulation of signal transduction pathways and antiviral responses. Identification and characterization of ubiquitinated viral proteins is an important step in understanding novel mechanisms of viral protein regulation as well as elucidating cellular antiviral strategies. Here we describe a protocol to easily detect and characterize the ubiquitination status of a v ...201121855635
Notification of the first isolation of Cacipacore virus in a human in the State of Rondônia, Brazil.Flavivirus is a genus of arthropod-transmitted viruses of the family Flaviviridae, and in Brazil, up to eleven different Flavivirus have been isolated. We collected blood from farmers in the municipality of Theobroma, which is located 320km from the City of Porto Velho, the former capital of the Brazilian State of Rondônia. For viral isolation, we used newborn mouse brain, followed by RT-PCR with specific universal Flavivirus primers. We obtained fragments 958bp and 800bp in length. Based on BLA ...201121860907
Inhibition of dengue virus by targeting viral NS4B protein.We report a novel inhibitor that selectively suppresses dengue virus (DENV) by targeting viral NS4B protein. The inhibitor was identified by screening a 1.8-million-compound library using a luciferase replicon of DENV serotype 2 (DENV-2). The compound specifically inhibits all four serotypes of DENV (50% effective concentration [EC(50)], 1 to 4 µM; and 50% cytotoxic concentration [CC(50)], >40 µM), but it does not inhibit closely related flaviviruses (West Nile virus and yellow fever virus) or n ...201121865382
heterogeneous nuclear ribonucleoprotein a2 participates in the replication of japanese encephalitis virus through an interaction with viral proteins and rna.japanese encephalitis virus (jev) is a mosquito-borne flavivirus that is kept in a zoonotic transmission cycle between pigs and mosquitoes. jev causes infection of the central nervous system with a high mortality rate in dead-end hosts, including humans. many studies have suggested that the flavivirus core protein is not only a component of nucleocapsids but also an important pathogenic determinant. in this study, we identified heterogeneous nuclear ribonucleoprotein a2 (hnrnp a2) as a binding p ...201121865391
Usutu virus: potential risk of human disease in Europe.Usutu virus (USUV) is an African mosquito-borne flavivirus, member of the Japanese encephalitis antigenic group. This avian virus is transmitted by arthropod vectors (mainly mosquitoes of the Culex pipiens complex). It is well known that free-living birds, including migratory species, have the potential to disperse certain pathogenic microorganisms. Usutu virus has recently been introduced to Europe and is spreading through Austria, Hungary, Italy, Spain and Switzerland, causing disease in birds ...201121871214
A fusion-loop antibody enhances the infectious properties of immature flavivirus particles.Flavivirus-infected cells secrete a mixture of mature, partially immature, and fully immature particles into the extracellular space. Although mature virions are highly infectious, prM-containing fully immature virions are noninfectious largely because the prM protein inhibits the cell attachment and fusogenic properties of the virus. If, however, cell attachment and entry are facilitated by anti-prM antibodies, immature flavivirus becomes infectious after efficient processing of the prM protein ...201121880758
The infectivity of prM-containing partially mature West Nile virus does not require the activity of cellular furin-like proteases.Cleavage of the flavivirus prM protein by a cellular furin-like protease is a hallmark of virion maturation. While this cleavage is a required step in the viral life cycle, it can be inefficient. Virions that retain uncleaved prM may be infectious. We investigated whether cleavage by furin of prM on partially mature West Nile virus (WNV) during virus entry contributes to infectivity. Using quantitative assays of WNV infection, we found that virions incorporating considerable amounts of uncleaved ...201121880759
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
rhabdomyolysis and severe muscular weakness in a traveler diagnosed with alkhurma hemorrhagic fever virus infection.alkhurma hemorrhagic fever virus (ahfv) is a tick-borne flavivirus with high case fatality rates, endemic in the arabian peninsula. recently ahfv was detected in travelers returning from egypt suggesting geographical spreading. we also report ahfv infection in a traveler ex egypt, representing atypical symptoms of rhabdomyolysis and severe muscular weakness.201121889906
a dna-based west nile virus replicon elicits humoral and cellular immune responses in mice.while self-replicating, non-infectious subgenomic flavivirus replicons have been described, most of them are rna transcripts under the control of an sp6 or t7 promoter. in this study, using west nile virus (wnv) as a model, a series of dna-based reporter replicons under the control of a minimal cytomegalovirus (cmv) immediate-early promoter were constructed, and functional analysis showed that these reporter replicons replicate efficiently in mammalian cells. when the dna-based wnv replicon was ...201121893098
Second external quality assessment of the molecular diagnostic of West Nile virus: are there improvements towards the detection of WNV?WNV epidemics occur worldwide, new WNV isolates were isolated in southern-east Europe belonging to WNV lineage 2. A first international proficiency study on WNV indicted that some laboratories were not able to detect WNV lineage 2 virus genome by their PCR diagnostic assays. Therefore an actual External Quality Assessment with both virus lineages was performed to monitor the improvements in molecular diagnostics.201121893429
dengue-2 and yellow fever 17dd viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different tnf-α and ifn-α profiles.flaviviruses cause severe acute febrile and haemorrhagic infections, including dengue and yellow fever and the pathogenesis of these infections is caused by an exacerbated immune response. dendritic cells (dcs) are targets for dengue virus (denv) and yellow fever virus (yf) replication and are the first cell population to interact with these viruses during a natural infection, which leads to an induction of protective immunity in humans. we studied the infectivity of denv2 (strain 16681), a yf v ...201121894381
Isolation of usutu virus in Germany.Usutu virus (USUV) is a mosquito-borne flavivirus that emerged 2001 in Austria and caused deaths in wild birds. In Germany, 70,378 female mosquitoes were captured in 2009 and 2010 and assayed for USUV. Virus was isolated in cell culture from one pool of Culex pipiens pipiens mosquitoes trapped exclusively in August 2010 in Weinheim, Germany. Subsequent phylogenetic analysis demonstrated a close relationship between the isolated USUV strain from Germany and a USUV strain from Austria, which was d ...201121896821
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
Alterations in the Aedes aegypti transcriptome during infection with West Nile, dengue and yellow fever viruses.West Nile (WNV), dengue (DENV) and yellow fever (YFV) viruses are (re)emerging, mosquito-borne flaviviruses that cause human disease and mortality worldwide. Alterations in mosquito gene expression common and unique to individual flaviviral infections are poorly understood. Here, we present a microarray analysis of the Aedes aegypti transcriptome over time during infection with DENV, WNV or YFV. We identified 203 mosquito genes that were = 5-fold differentially up-regulated (DUR) and 202 genes t ...201121909258
Dengue virus capsid protein binds core histones and inhibits nucleosome formation in human liver cells.Dengue virus (DENV) is a member of the Flaviviridae and a globally (re)emerging pathogen that causes serious human disease. There is no specific antiviral or vaccine for dengue virus infection. Flavivirus capsid (C) is a structural protein responsible for gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. Flaviviral replication is known to occur in the cytoplasm yet a large portion of capsid protein localizes to the nucleus during infection. The reasons f ...201121909430
west nile virus: north american experience.west nile virus, a mosquito-vectored flavivirus of the japanese encephalitis serogroup, was first detected in north america following an epizootic in the new york city area in 1999. in the intervening 11 years since the arrival of the virus in north america, it has crossed the contiguous usa, entered the canadian provinces bordering the usa, and has been reported in the caribbean islands, mexico, central america and, more recently, south america. west nile virus has been reported in over 300 spe ...201121910847
poorly neutralizing cross-reactive antibodies against the fusion loop of west nile virus envelope protein protect in vivo via fcgamma receptor and complement-dependent effector mechanisms.the human antibody response to flavivirus infection is dominantly directed against a cross-reactive epitope on the fusion loop of domain ii (dii-fl) of the envelope (e) protein. although antibodies against this epitope fail to recognize fully mature west nile virus (wnv) virions and accordingly neutralize infection poorly in vitro, their functional properties in vivo remain less well understood. here, we show that while passive transfer of poorly neutralizing monoclonal antibodies (mab) and poly ...201121917960
a cross-protective mab recognizes a novel epitope within the flavivirus ns1 protein.despite a resurgence of flavivirus infections worldwide, no approved therapeutic agent exists for any member of the genus. while cross-reactive antibodies with therapeutic potential against flaviviruses have been generated, the majority of them are anti-e antibodies with the potential to cause antibody-dependent enhancement of flavivirus infection and disease. we described previously mabs against the non-structural ns1 protein of the west nile virus (wnv) that were protective in mice when admini ...201221918007
TRIMming Flavivirus infection.Tripartite motif (TRIM) proteins are novel players in antiviral innate immunity. In this issue of Cell Host & Microbe,Taylor et al. (2011) discover the mechanism of action of TRIM79a and show that this interferon-induced protein restricts tick-borne flaviviruses by targeting the viral polymerase for degradation.201121925103
trim79α, an interferon-stimulated gene product, restricts tick-borne encephalitis virus replication by degrading the viral rna polymerase.in response to virus infection, type i interferons (ifns) induce several genes, most of whose functions are largely unknown. here, we show that the tripartite motif (trim) protein, trim79α, is an ifn-stimulated gene (isg) product that specifically targets tick-borne encephalitis virus (tbev), a flavivirus that causes encephalitides in humans. trim79α restricts tbev replication by mediating lysosome-dependent degradation of the flavivirus ns5 protein, an rna-dependent rna polymerase essential for ...201121925107
flavivirus rna cap methyltransferase: structure, function, and inhibition.many flaviviruses are significant human pathogens. the plus-strand rna genome of a flavivirus contains a 5' terminal cap 1 structure (m(7)gpppamg). the flavivirus encodes one methyltransferase (mtase), located at the n-terminal portion of the ns5 rna-dependent rna polymerase (rdrp). here we review recent advances in our understanding of flaviviral capping machinery and the implications for drug development. the ns5 mtase catalyzes both guanine n7 and ribose 2'-oh methylations during viral cap fo ...201021927615
cell entry of enveloped viruses.infection of cells by enveloped viruses requires merger of the viral envelope membrane with target cell membranes, resulting in the formation of fusion pores through which the viral genome is released. since lipid membranes do not mix spontaneously, the fusion process is energy-dependent and mediated by viral envelope glycoprotein complexes. based on their structural and mechanistic properties, three distinct classes of viral fusion proteins have been identified to date. despite their diversity, ...201121927634
West Nile virus genetic diversity is maintained during transmission by Culex pipiens quinquefasciatus mosquitoes.Due to error-prone replication, RNA viruses exist within hosts as a heterogeneous population of non-identical, but related viral variants. These populations may undergo bottlenecks during transmission that stochastically reduce variability leading to fitness declines. Such bottlenecks have been documented for several single-host RNA viruses, but their role in the population biology of obligate two-host viruses such as arthropod-borne viruses (arboviruses) in vivo is unclear, but of central impor ...201121935412
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
evidence of efficient transovarial transmission of culex flavivirus by culex pipiens (diptera: culicidae).this study determined the transovarial transmission (tot) potential and tissue tropisms of culex flavivirus (cxfv), an insect-specific flavivirus, in culex pipiens (l.). several hundred mosquito egg rafts were collected in the field, transferred to the insectaries, reared to the fourth larval instar, and identified using morphological characteristics. cx. pipiens were reared to adults, allowed to oviposit in individual containers, and tested for cxfv rna by reverse transcription-polymerase chain ...201121936322
temporal and spatial patterns of west nile virus transmission in saginaw county, michigan, 2003-2006.the dynamics of west nile virus (family flaviviridae, genus flavivirus, wnv) infection in mosquitoes, sentinel pheasants, and wild dead birds were evaluated during 2003-2006 in saginaw co., mi. mosquitoes were collected by new jersey light traps at 22 sites during may-september, pooled by species and sample location, and tested for presence of wnv rna by using a real-time reverse transcription-polymerase chain reaction assay. oral swabs from wild dead birds submitted by the public were tested by ...201121936324
Nonconsensus West Nile virus genomes arising during mosquito infection suppress pathogenesis and modulate virus fitness in vivo.West Nile virus (WNV) is similar to other RNA viruses in that it forms genetically complex populations within hosts. The virus is maintained in nature in mosquitoes and birds, with each host type exerting distinct influences on virus populations. We previously observed that prolonged replication in mosquitoes led to increases in WNV genetic diversity and diminished pathogenesis in mice without remarkable changes to the consensus genome sequence. We therefore sought to evaluate the relationships ...201121937657
association of heat-shock protein 70 with lipid rafts is required for japanese encephalitis virus infection in huh7 cells.japanese encephalitis virus (jev) is an enveloped flavivirus and the most common agent of viral encephalitis. it enters cells through receptor-mediated endocytosis and low ph-triggered membrane fusion. although lipid rafts, cholesterol-enriched lipid-ordered membrane domains, have been shown to participate in jev entry, the mechanisms of the early events of jev infection, including the cellular receptors of jev, remain largely unknown. in the current study, it was demonstrated that heat-shock pr ...201221940409
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
Mice with different susceptibility to Japanese encephalitis virus infection show selective neutralizing antibody response and myeloid cell infectivity.Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes public health problems in Asian countries. Only a limited number of JEV-infected individuals show symptoms and develop severe encephalitis, indicating host-dependent susceptibilities.201121949747
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
a conserved region in the prm protein is a critical determinant in the assembly of flavivirus particles.flaviviruses are assembled to bud into the lumen of the endoplasmic reticulum (er) and are secreted through the vesicle transport pathway, but the details of the molecular mechanism of virion assembly remain largely unknown. in this study, a highly conserved region in the prm protein was identified among flaviviruses. in the subviral particle (sp) system of tick-borne encephalitis virus (tbev) and japanese encephalitis virus, secretion of sps was impaired by a mutation in the conserved region in ...201221957123
quantitative mass spectrometry of denv-2 rna-interacting proteins reveals that the dead-box rna helicase ddx6 binds the db1 and db2 3' utr structures.dengue virus (denv) is a rapidly re-emerging flavivirus that causes dengue fever (df), dengue hemorrhagic fever (dhf) and dengue shock syndrome (dss), diseases for which there are no available therapies or vaccines.  the denv-2 positive-strand rna genome contains 5' and 3' untranslated regions (utrs) that have been shown to form secondary structures required for virus replication and interaction with host cell proteins.  in order to comprehensively identify host cell factors that bind the denv-2 ...201121957497
Tick-borne encephalitis increasing in Sweden, 2011. 201121968422
Tick-borne encephalitis in Europe, 2007 to 2009. 201121968423
priming effect of dengue and yellow fever vaccination on the immunogenicity, infectivity, and safety of a tetravalent dengue vaccine in humans.a dengue vaccine effective against all four serotypes is urgently needed. however, safety and immunogenicity could be affected by prior exposure to flaviviruses. this open, controlled, phase iia study was conducted in 35 healthy adults who had received monovalent, live attenuated vero cell-derived dengue vaccine against dengue virus 1 (vdv1) or 2 (vdv2) or yellow fever (yf) vaccine 1 year before or who were flavivirus-naïve. all participants received one subcutaneous injection of tetravalent den ...201121976579
Establishing a TaqMan-based real-time PCR assay for the rapid detection and quantification of the newly emerged duck Tembusu virus.To establish an accurate, rapid, and a quantifiable method for the detection of the newly emerged duck Tembusu virus (DTMUV) that recently caused a widespread infectious disease in ducks in China, we developed a TaqMan-based real-time PCR assay by using E gene-specific primers and a TaqMan probe. This real-time PCR assay was 100 times more sensitive than the conventional PCR. The reproducibility and specificity of the real-time PCR assay were confirmed using plasmids containing E genes or RNAs a ...201121978536
the first report of west nile virus infection in a child from turkey.seroprevalence data indicate that west nile virus (wnv) activity is present in turkey; however, no pediatric cases of wnv infection have been reported to date. wnv is an emerging flavivirus in turkey, and in september2010, the turkish ministry of health reported the first seven cases of laboratory-confirmed wnv infection from five different cities in the western part of the country. this is the first report of a child from central anatolia, indicating the existence of the virus in other regions ...201121980815
incidence and seroprevalence of dengue virus infections in australian travellers to asia.the purpose of this study was to estimate the incidence density and prevalence of dengue virus infection in australian travellers to asia. we conducted a multi-centre prospective cohort study of australian travellers over a 32-month period. we recruited 467 travellers (≥16 years of age) from three travel clinics who intended to travel asia, and 387 (82.9%) of those travellers completed questionnaires and provide samples pre- and post-travel for serological testing for dengue virus infection. dem ...201121983919
preexisting japanese encephalitis virus neutralizing antibodies and increased symptomatic dengue illness in a school-based cohort in thailand.dengue viruses (denvs) and japanese encephalitis virus (jev) have significant cross-reactivity in serological assays; the clinical implications of this remain undefined. an improved understanding of whether and how jev immunity modulates the clinical outcome of denv infection is important as large-scale denv vaccine trials will commence in areas where jev is co-endemic and/or jev immunization is routine.201121991398
how flaviviruses activate and suppress the interferon response.the flavivirus genus includes viruses with a remarkable ability to produce disease on a large scale. the expansion and increased endemicity of dengue and west nile viruses in the americas exemplifies their medical and epidemiological importance. the rapid detection of viral infection and induction of the innate antiviral response are crucial to determining the outcome of infection. the intracellular pathogen receptors rig-i and mda5 play a central role in detecting flavivirus infections and init ...201021994652
West Nile virus: immunity and pathogenesis.West Nile virus (WNV) is a neurotropic, arthropod-borne flavivirus that is maintained in an enzootic cycle between mosquitoes and birds, but can also infect and cause disease in horses and humans. WNV is endemic in parts of Africa, Europe, the Middle East, and Asia, and since 1999 has spread to North America, Mexico, South America, and the Caribbean. WNV infects the central nervous system (CNS) and can cause severe disease in a small minority of infected humans, mostly immunocompromised or the e ...201121994755
Dengue--quo tu et quo vadis?Dengue viruses (DENV) are by far the most important arboviral pathogens in the tropics around the world, putting at risk of infection nearly a third of the global human population. DENV are members of the genus Flavivirus in the Family Flaviviridae and comprise four antigenically distinct serotypes (DENV-1-4). Although they share almost identical epidemiological features, they are genetically distinct. Phylogenetic analyses have revealed valuable insights into the origins, epidemiology and the f ...201121994796
Association of human immune response to Aedes aegypti salivary proteins with dengue disease severity.Dengue viruses (DENV; family Flaviviridae, genus Flavivirus) are transmitted by Aedes aegypti mosquitoes and can cause dengue fever (DF), a relatively benign disease, or more severe dengue haemorrhagic fever (DHF). Arthropod saliva contains proteins delivered into the bite wound that can modulate the host haemostatic and immune responses to facilitate the intake of a blood meal. The potential effects on DENV infection of previous exposure to Ae. aegypti salivary proteins have not been investigat ...201221995849
dnaj homolog hdj2 facilitates japanese encephalitis virus replication.japanese encephalitis virus (jev) is a member of the mosquito-borne flaviviridae family of viruses that causes human encephalitis. upon infection of a new host, replication of viral rna involves not only the viral rna-dependent rna polymerase (rdrp), but also host proteins. host factors involved in jev replication are not well characterized.201121999493
Analyses of mutations selected by passaging a chimeric flavivirus identify mutations that alter infectivity and reveal an interaction between the structural proteins and the nonstructural glycoprotein NS1.We previously described a single-cycle dengue vaccine (RepliVAX D2) engineered from a capsid (C) gene-deleted West Nile virus (WNV) expressing dengue virus serotype 2 (DENV2) prM/E genes in place of the corresponding WNV genes. That work demonstrated that adaptation of RepliVAX D2 to grow in WNV C-expressing cells resulted in acquisition of non-synonymous mutations in the DENV2 prM/E and WNV NS2A/NS3 genes. Here we demonstrate that the prM/E mutations increase the specific infectivity of chimeri ...201121999990
Tembusu virus in ducks, china.In China in 2010, a disease outbreak in egg-laying ducks was associated with a flavivirus. The virus was isolated and partially sequenced. The isolate exhibited 87%-91% identity with strains of Tembusu virus, a mosquito-borne flavivirus of the Ntaya virus group. These findings demonstrate emergence of Tembusu virus in ducks.201122000358
Detection of West Nile virus genome and specific antibodies in Iranian encephalitis patients.SUMMARYWest Nile virus (WNV) is a mosquito-borne flavivirus which circulates in birds, horses and humans. An estimated 80% of WNV infections are asymptomatic. Fewer than 1% of infected persons develop neuroinvasive disease, which typically presents as encephalitis, meningitis, or acute flaccid paralysis. This study was conducted from January 2008 to June 2009 in Isfahan, Iran. Patients attending the emergency department with fever and loss of consciousness were consecutively included. Cerebrospi ...201122008154
Neurovirulent flavivirus can be attenuated in mice by incorporation of neuron-specific microRNA recognition elements into viral genome.Engineering viruses by inserting microRNA (miRNA) recognition elements (MREs) into the 3'-untranslated region (3'-UTR) of viral RNA can efficiently restrict viral tissue tropism. We used the mosquito-borne Japanese encephalitis virus (JEV) to investigate whether endogenous neuron-specific microRNA-124 (miR-124) could be used to restrict viral neurotropism and, consequently, diminish the neurovirulence of JEV in mice. To recover a neuron-restricted JEV, we inserted 2 copies of a perfectly matched ...201122008823
Molecular evolution of the insect-specific flaviviruses.There has been an explosion in the discovery of 'insect-specific' flaviviruses and/or their related sequences in natural mosquito populations. Herein we review all 'insect-specific' flaviviral sequences currently available and conduct phylogenetic analyses of both the 'insect-specific' flaviviruses and available sequences of the entire genus Flavivirus. We show that there is no statistical support for virus-mosquito co-divergence, suggesting that the 'insect-specific' flaviviruses may have under ...201122012464
flavivirus ns3 and ns5 proteins interaction network: a high-throughput yeast two-hybrid screen.the genus flavivirus encompasses more than 50 distinct species of arthropod-borne viruses, including several major human pathogens, such as west nile virus, yellow fever virus, japanese encephalitis virus and the four serotypes of dengue viruses (denv type 1-4). each year, flaviviruses cause more than 100 million infections worldwide, some of which lead to life-threatening conditions such as encephalitis or haemorrhagic fever. among the viral proteins, ns3 and ns5 proteins constitute the major e ...201122014111
Analysis of RNA binding by the dengue virus NS5 RNA capping enzyme.Flaviviruses are small, capped positive sense RNA viruses that replicate in the cytoplasm of infected cells. Dengue virus and other related flaviviruses have evolved RNA capping enzymes to form the viral RNA cap structure that protects the viral genome and directs efficient viral polyprotein translation. The N-terminal domain of NS5 possesses the methyltransferase and guanylyltransferase activities necessary for forming mature RNA cap structures. The mechanism for flavivirus guanylyltransferase ...201122022449
novel flaviviruses detected in different species of mosquitoes in spain.abstract we report the characterization of three novel flaviviruses isolated in spain. marisma mosquito virus, a novel mosquito borne virus, was isolated from ochlerotatus caspius mosquitoes; spanish ochlerotatus flavivirus and spanish culex flavivirus, two novel insect flaviviruses, were isolated from oc. caspius and culex pipiens, respectively. during this investigation, we designed a sensitive rt-nested polymerase chain reaction method that amplifies a 1019bp fragment of the flavivirus ns5 ...201122022811
Serologic survey of humans for flavivirus West Nile in Southern Moravia (Czech Republic).A serosurvey for West Nile virus (WNV) was carried out in 525 persons, using a plaque-reduction neutralization microtest (PRNmicroT) with Vero cells and Egyptian topotype Eg-101 strain as test virus. The blood sera were collected in four South-Moravian districts (Hodonin 44 persons, Breclav 102 persons, Znojmo 170 persons, Jihlava 209 persons) of the Czech Republic in the years 1988 and 1989, and stored at -20 degrees C. Antibodies to WNV were detected in only three humans (0.6% seropositivity): ...201122026285
Broad-spectrum antiviral activity of RNA interference against four genotypes of Japanese encephalitis virus based on single microRNA polycistrons.Japanese encephalitis virus (JEV), a neurotropic mosquito-borne flavivirus, causes acute viral encephalitis and neurologic disease with a high fatality rate in humans and a range of animals. Small interfering RNA (siRNA) is a powerful antiviral agent able to inhibit JEV replication. However, the high rate of genetic variability between JEV strains (of four confirmed genotypes, genotypes I, II, III and IV) hampers the broad-spectrum application of siRNAs, and mutations within the targeted sequenc ...201122028851
induction of a protective response in mice by the dengue virus ns3 protein using dna vaccines.the dengue non-structural 3 (ns3) is a multifunctional protein, containing a serino-protease domain, located at the n-terminal portion, and helicase, ntpase and rtpase domains present in the c-terminal region. this protein is considered the main target for cd4+ and cd8+ t cell responses during dengue infection, which may be involved in protection. however, few studies have been undertaken evaluating the use of this protein as a protective antigen against dengue, as well as other flavivirus. in t ...201122031819
Ligand-bound structures of the dengue virus protease reveal the active conformation.Dengue is a mosquito-borne viral hemorrhagic disease that is a major threat to human health in tropical and subtropical regions. Here we report crystal structures of a peptide covalently bound to dengue virus serotype 3 (DENV-3) protease as well as the serine-protease inhibitor aprotinin bound to the same enzyme. These structures reveal, for the first time, a catalytically active, closed conformation of the DENV protease. In the presence of the peptide, the DENV-3 protease forms the closed confo ...201222031935
pestivirus virion morphogenesis in the absence of uncleaved nonstructural protein 2-3.the family flaviviridae contains three genera of positive-strand rna viruses, namely, flavivirus, hepacivirus (e.g., hepatitis c virus [hcv]), and pestivirus. pestiviruses, like bovine viral diarrhea virus (bvdv), bear a striking degree of similarity to hcv concerning polyprotein organization, processing, and function. along this line, in both systems, release of nonstructural protein 3 (ns3) is essential for viral rna replication. however, both viruses differ significantly with respect to proce ...201222031952
a thiopurine drug inhibits west nile virus production in cell culture, but not in mice.many viruses within the flavivirus genus cause significant disease in humans; however, effective antivirals against these viruses are not currently available. we have previously shown that a thiopurine drug, 6-methylmercaptopurine riboside (6mmpr), inhibits replication of distantly related viruses within the flaviviridae family in cell culture, including bovine viral diarrhea virus and hepatitis c virus replicon. here we further examined the potential antiviral effect of 6mmpr on several diverse ...201122039536
quinoline tricyclic derivatives. design, synthesis and evaluation of the antiviral activity of three new classes of rna-dependent rna polymerase inhibitors.in this study three new classes of linear n-tricyclic compounds, derived by condensation of the quinoline nucleus with 1,2,3-triazole, imidazole or pyrazine, were synthesized, obtaining triazolo[4,5-g]quinolines, imidazo[4,5-g]quinolines and pyrido[2,3-g]quinoxalines, respectively. title compounds were tested in cell-based assays for cytotoxicity and antiviral activity against rna viruses representative of the three genera of the flaviviridae family, that is bvdv (pestivirus), yfv (flavivirus) a ...201122047799
flavivirus cell entry and membrane fusion.flaviviruses, such as dengue virus and west nile virus, are enveloped viruses that infect cells through receptor-mediated endocytosis and fusion from within acidic endosomes. the cell entry process of flaviviruses is mediated by the viral e glycoprotein. this short review will address recent advances in the understanding of flavivirus cell entry with specific emphasis on the recent study of zaitseva and coworkers, indicating that anionic lipids might play a crucial role in the fusion process of ...201122049308
Single nucleotide polymorphism in the promoter region of the CD209 gene is associated with human predisposition to severe forms of tick-borne encephalitis.Tick-borne encephalitis virus (TBEV) is a neurotropic, positive-sense RNA virus of the genus Flavivirus (family Flaviviridae) which can cause a variety of clinical manifestations in humans. Previously the severity and outcome of dengue fever and hepatitis C (diseases caused by viruses from the family Flaviviridae) were associated with the rs4804803 single nucleotide polymorphism (SNP) located in the promoter region of the human CD209 gene. This gene encodes dendritic cell-specific ICAM3-grabbing ...201222061615
Recombination in hepatitis C virus.Hepatitis C virus (HCV) is a Flavivirus with a positive-sense, single-stranded RNA genome of about 9,600 nucleotides. It is a major cause of liver disease, infecting almost 200 million people all over the world. Similarly to most RNA viruses, HCV displays very high levels of genetic diversity which have been used to differentiate six major genotypes and about 80 subtypes. Although the different genotypes and subtypes share basic biological and pathogenic features they differ in clinical outcomes ...201122069526
Uncoupling cis-Acting RNA Elements from Coding Sequences Revealed a Requirement of the N-Terminal Region of Dengue Virus Capsid Protein in Virus Particle Formation.Little is known about the mechanism of flavivirus genome encapsidation. Here, functional elements of the dengue virus (DENV) capsid (C) protein were investigated. Study of the N-terminal region of DENV C has been limited by the presence of overlapping cis-acting RNA elements within the protein-coding region. To dissociate these two functions, we used a recombinant DENV RNA with a duplication of essential RNA structures outside the C coding sequence. By the use of this system, the highly conserve ...201222072762
West Nile virus encodes a microRNA-like small RNA in the 3' untranslated region which up-regulates GATA4 mRNA and facilitates virus replication in mosquito cells.West Nile virus (WNV) belongs to a group of medically important single-stranded, positive-sense RNA viruses causing deadly disease outbreaks around the world. The 3' untranslated region (3'-UTR) of the flavivirus genome, in particular the terminal 3' stem-loop (3'SL) fulfils multiple functions in virus replication and virus-host interactions. Using the Kunjin strain of WNV (WNV(KUN)), we detected a virally encoded small RNA, named KUN-miR-1, derived from 3'SL. Transcription of WNV(KUN) pre-miRNA ...201122080551
rna interference inhibits replication of tick-borne encephalitis virus in vitro.each year, up to 10,000 cases of infections with the flavivirus tick-borne encephalitis (tbe) virus that affect the central nervous system are reported in europe and asia. due to the potentially severe adverse effects of post-exposure prophylaxis with tbe virus hyperimmunoglobulin, tbe can currently only be treated symptomatically. an rna interference (rnai) approach to inhibit tbe virus replication was therefore developed. in this study we demonstrate for the first time that small interfering r ...201222086130
Neuroinvasive flavivirus infections.Flaviviruses, including Dengue, West Nile, Japanese encephalitis, and Tick-borne encephalitis virus, are major emerging human pathogens, affecting millions of individuals worldwide. Many clinically important flaviviruses elicit CNS diseases in infected hosts, including traditional "hemorrhagic" viruses, such as Dengue. This review focuses on the epidemiology, symptomatology, neuropathology, and, specifically, neuropathogenesis of flavivirus-induced human CNS disease. A detailed insight into spec ...201122086854
expression and immunoaffinity purification of recombinant dengue virus 2 ns1 protein as a cleavable sumostar fusion.dengue virus (denv) encoded nonstructural one (ns1) is a 352 amino acid protein that exists in multiple oligomeric states and is conserved within the flavivirus family. although ns1 has been heavily researched for its diagnostic utility, there is a gap in the understanding of its role in a range of viral processes, including replication and development of clinical pathologies such as vascular leakage. many of these functions involve unknown interactions with viral and host proteins. this study d ...201122100526
analysis of the complete genome of tembusu virus, a flavivirus isolated from ducks in china.during investigations into the outbreak of duck viral infection in 2010 in china, with a severe drop in egg production, a flavivirus was isolated from the affected ducks. it was characterized as a tembusu virus (tmuv). in this study, we obtained a complete genome sequence of tembusu virus using rt-pcr and race techniques. tmuv genome is a singled-stranded rna, with 10 990 nucleotides in length, and contains a single open reading frame (3410 amino acids) encoding 11 viral proteins with 5'and 3'no ...201122103739
Class II ADP-ribosylation Factors Are Required for Efficient Secretion of Dengue Viruses.Identification and characterization of virus-host interactions are very important steps toward a better understanding of the molecular mechanisms responsible for disease progression and pathogenesis. To date, very few cellular factors involved in the life cycle of flaviviruses, which are important human pathogens, have been described. In this study, we demonstrate a crucial role for class II Arf proteins (Arf4 and Arf5) in the dengue flavivirus life cycle. We show that simultaneous depletion of ...201222105072
Neuralgic amyotrophy associated with dengue fever: Case series of three patients.Dengue is an acute mosquito borne viral infection caused by one of the four distinct serotype of dengue viruses (type 1-4), belonging to flavivirus family. Dengue fever, an arboviral infection is known to cause various neurological complications. Commonly reported neurological manifestations associated with dengue infection are encephalopathy, myelopathy, stroke, Guillain-Barre syndrome and hypokalemic paralysis. Brachial amyotrophy associated with dengue infection were not described previously. ...201122120863
Serosurveillance for Japanese encephalitis virus in wild birds captured in Korea.Climate change induced by recent global warming may have a significant impact on vector-borne and zoonotic diseases. For example, the distribution of Japanese encephalitis virus (JEV) has expanded into new regions. We surveyed the levels of hemagglutination-inhibition (HI) antibodies against JEV (Family Flaviviridae, genus Flavivirus) in wild birds captured in Korea. Blood samples were collected from 1,316 wild birds including the following migratory birds: Oceanodroma castro (n = 4), Anas formo ...201122122903
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
Displaying items 3201 - 3300 of 3318