| effect of sequential exposure on infection and dissemination rates for west nile and st. louis encephalitis viruses in culex quinquefasciatus. | west nile virus has spread rapidly throughout the united states since its introduction in 1999, into some areas that are also endemic for st. louis encephalitis virus (slev). these viruses are in the same antigenic complex within the genus flavivirus, family flaviviridae. further, both viruses are transmitted primarily by culex spp. mosquitoes and use birds as amplifying hosts. these viruses could contemporaneously coinfect individual vectors wherein changes in mosquito immune responses might oc ... | 2009 | 19492941 |
| serologic surveillance for west nile virus and other flaviviruses in febrile patients, encephalitic patients, and asymptomatic blood donors in northern mexico. | a clinical and serological investigation was performed to determine the presence of west nile virus (wnv) among febrile and encephalitic patients in northern mexico. in addition, asymptomatic blood donors were serologically assayed for wnv to determine the seroprevalence of wnv in the general population. the study cohort consisted of 1432 individuals (588 febrile patients, 44 encephalitic patients, and 800 asymptomatic blood donors). all subjects were negative for wnv igm. sixty subjects were re ... | 2010 | 19492946 |
| flavivirus rna in phlebotomine sandflies. | sandfly-transmitted phleboviruses, such as toscana, sandfly fever sicilian, and sandfly fever naples, can cause human disease and circulate at high rates in mediterranean countries. previous studies have also established that viruses other than phleboviruses may be detected in and isolated from sand flies. the recent detection and isolation (in a large variety of mosquito species) of insect-only flaviviruses related to cell fusing agent virus has indicated that the latter is not an evolutionary ... | 2010 | 19492949 |
| longitudinal studies of japanese encephalitis virus infection in vector mosquitoes in kurnool district, andhra pradesh, south india. | a 4-yr (2002-2006) entomological study was carried out in kurnool district, andhra pradesh state, south india, to identify the mosquito vectors of japanese encephalitis virus (family flaviviridae, genus flavivirus, jev). in total, 37,139 female mosquitoes belonging five genera and 18 species resting on vegetation were collected in villages and periurban areas at dusk. mosquito species composition and pattern of jev infection in mosquitoes varied in periurban and rural areas. in periurban area, c ... | 2009 | 19496437 |
| surveillance of mosquito-borne viruses in alberta using reverse transcription polymerase chain reaction with generic primers. | mosquitoes collected during 2003, 2004, and 2005 in alberta, canada, were screened for the presence of a wide range of arboviruses by reverse transcription-polymerase chain reaction (rt-pcr). nucleic acid extracts from mosquito slurries were amplified using universal primers designed to detect viruses belonging to the flavivirus genus of the flaviviridae family and california and bunyamwera serogroups of the bunyavirus genus within the bunyaviridae family. species-specific detection of western e ... | 2009 | 19496438 |
| coimmunization with an optimized il15 plasmid adjuvant enhances humoral immunity via stimulating b cells induced by genetically engineered dna vaccines expressing consensus jev and wnv e diii. | the japanese encephalitis virus (jev) and west nile virus (wnv) are responsible for a large proportion of viral encephalitis in humans. currently, there is no fda approved specific treatment for either, though there are attempts to develop vaccines against both viruses. in this study, we proposed novel genetically engineered dna vaccines against these two neurotrophic flaviviruses. the structural domain iii (diii) of e protein from these viruses is reported to carry dominant epitopes that induce ... | 2009 | 19497647 |
| flaviviral methyltransferase/rna interaction: structural basis for enzyme inhibition. | flaviviruses are the causative agents of severe diseases such as dengue or yellow fever. the replicative machinery used by the virus is based on few enzymes including a methyltransferase, located in the n-terminal domain of the ns5 protein. flaviviral methyltransferases are involved in the last two steps of the mrna capping process, transferring a methyl group from s-adenosyl-l-methionine onto the n7 position of the cap guanine (guanine-n7 methyltransferase) and the ribose 2'o position of the fi ... | 2009 | 19501254 |
| identification and characterization of inhibitors of west nile virus. | although flaviviruses cause significant human diseases, no antiviral therapy is currently available for clinical treatment of these pathogens. to identify flavivirus inhibitors, we performed a high-throughput screening of compound libraries using cells containing luciferase-reporting replicon of west nile viruses (wnv). five novel small molecular inhibitors of wnv were identified from libraries containing 96,958 compounds. the inhibitors suppress epidemic strain of wnv in cell culture, with ec(5 ... | 2009 | 19501258 |
| meningitis determined by oligosymptomatic dengue virus type 3 infection: report of a case. | dengue infection is a mosquito-borne disease caused by a flavivirus, and is recognized in over 100 countries with 2.5 billion people living in areas of risk. neurological manifestations such as encephalitis, myelitis, guillain-barré syndrome, cranial nerve palsies, neuromyelitis optica, and encephalomyelitis have been recognized as clinical consequences of dengue infection. meningitis is a rare complication. we report the case of a 24-year-old woman who presented with fever, headache, and nuchal ... | 2010 | 19501535 |
| antibodies to flaviviruses in wild ducks captured in hokkaido, japan: risk assessment of invasive flaviviruses. | recently, the distribution of japanese encephalitis virus (jev) and west nile virus (wnv) has expanded into new territories. the invasion of wnv into japan is of great concern. the migration of birds is suggested to be involved in the expanded distribution of these flaviviruses. in this study, 92 wild ducks--20 anas poecilorhyncha (migratory breeders), 50 anas platyrhynchos (undetermined), 16 anas acuta (winter visitors), and 6 anas penelope (winter visitors)--were captured in autumn of 2005 and ... | 2009 | 19514809 |
| zika virus outbreak on yap island, federated states of micronesia. | in 2007, physicians on yap island reported an outbreak of illness characterized by rash, conjunctivitis, and arthralgia. although serum from some patients had igm antibody against dengue virus, the illness seemed clinically distinct from previously detected dengue. subsequent testing with the use of consensus primers detected zika virus rna in the serum of the patients but no dengue virus or other arboviral rna. no previous outbreaks and only 14 cases of zika virus disease have been previously d ... | 2009 | 19516034 |
| production of infectious genotype 1b virus particles in cell culture and impairment by replication enhancing mutations. | with the advent of subgenomic hepatitis c virus (hcv) replicons, studies of the intracellular steps of the viral replication cycle became possible. these rnas are capable of self-amplification in cultured human hepatoma cells, but save for the genotype 2a isolate jfh-1, efficient replication of these hcv rnas requires replication enhancing mutations (rems), previously also called cell culture adaptive mutations. these mutations cluster primarily in the central region of non-structural protein 5a ... | 2009 | 19521536 |
| ic51 japanese encephalitis vaccine. | japanese encephalitis is the leading cause of viral encephalitis in asia. every year 30,000 - 50,000 cases and 10,000 deaths from japanese encephalitis are reported, and underreporting has been suggested. no effective antiviral therapy exists to treat this mosquito-borne flavivirus infection. for active immunization vaccines are available. the manufacturing of the only vaccine that was internationally licensed, je-vax, was ceased in 2005. therefore a shortage of japanese encephalitis vaccines mi ... | 2009 | 19527110 |
| 2-arylbenzimidazoles as antiviral and antiproliferative agents--part 2. | in prosecution of an anti-flaviviridae project a new series of variously substituted 2-diphenyl-benzimidazoles were synthesized and tested in vitro for antiviral and antiproliferative activities. compounds were tested in cell-based assays against viruses representative of: i) two of the three genera of the flaviviridae family, i.e. flaviviruses and pestiviruses; ii) other rna virus families, such as retroviridae, picornaviridae, paramyxoviridae, rhabdoviridae and reoviridae; iii) two dna virus f ... | 2009 | 19534676 |
| hepatitis c virus core, ns3, ns4b and ns5a are the major immunogenic proteins in humoral immunity in chronic hcv infection. | the viral genome of hepatitis c virus constitutes a 9.6-kb single-stranded positive-sense rna which encodes altogether 11 viral proteins. in order to study the humoral immune responses against different hcv proteins in patients suffering from chronic hcv infection, we produced three structural (core, e1 and e2) and six nonstructural proteins (ns2, ns3, ns4a, ns4b, ns5a and ns5b) in sf9 insect cells by using the baculovirus expression system. | 2009 | 19549310 |
| cytokine and nitric oxide production by mouse macrophages infected with brazilian flaviviruses. | the flaviviridae family, flavivirus genus includes viruses that are transmitted to vertebrates by infected mosquitoes or ticks. the genus flavivirus includes a variety of viruses that cause diseases such as acute febrile illness, encephalitis, and hemorrhagic fever. flaviviruses primarily infect blood monocytes and tissue macrophages, which have been shown to be permissive, supporting viral replication and serving as virus reservoirs. on the other hand, these cells may have an important antivira ... | 2009 | 19551288 |
| impact of quaternary organization on the antigenic structure of the tick-borne encephalitis virus envelope glycoprotein e. | the envelope protein e of flaviviruses mediates both receptor-binding and membrane fusion. at the virion surface, 180 copies of e are tightly packed and organized in a herringbone-like icosahedral structure, whereas in noninfectious subviral particles, 60 copies are arranged in a t=1 icosahedral symmetry. in both cases, the basic building block is an e dimer which exposes the binding sites for neutralizing antibodies at its surface. it was the objective of our study to assess the dependence of t ... | 2009 | 19553320 |
| spatial distribution and risk factors of dengue and japanese encephalitis virus infection in urban settings: the case of vientiane, lao pdr. | to evaluate the prevalence of flavivirus infection in vientiane city (lao pdr), to describe the spatial distribution of infection within this city, and to explore the link between flavivirus seroprevalence and urbanization levels of residential neighbourhoods. | 2009 | 19563430 |
| characterization of a novel flavivirus from mosquitoes in northern europe that is related to mosquito-borne flaviviruses of the tropics. | a novel flavivirus was isolated from mosquitoes in finland, representing the first mosquito-borne flavivirus from northern europe. the isolate, designated lammi virus (lamv), was antigenically cross-reactive with other flaviviruses and exhibited typical flavivirus morphology as determined by electron microscopy. the genomic sequence of lamv was highly divergent from the recognized flaviviruses, and yet the polyprotein properties resembled those of mosquito-borne flaviviruses. phylogenetic analys ... | 2009 | 19570865 |
| genetic characterization of bagaza virus (bagv) isolated in india and evidence of anti-bagv antibodies in sera collected from encephalitis patients. | during investigations into the outbreak of encephalitis in 1996 in the kerala state in india, an arbovirus was isolated from a culex tritaeniorhynchus mosquito pool. it was characterized as a japanese encephalitis and west nile virus cross-reactive arbovirus by complement fixation test. a plaque reduction-neutralization test was performed using hyperimmune sera raised against the plaque-purified arbovirus isolate. the sera did not show reactivity with japanese encephalitis virus and were weakly ... | 2009 | 19570951 |
| flaviviral protease inhibitors identified by fragment-based library docking into a structure generated by molecular dynamics. | fragment-based docking was used to select a conformation for virtual screening from a molecular dynamics trajectory of the west nile virus nonstructural 3 protease. this conformation was chosen from an ensemble of 100 molecular dynamics snapshots because it optimally accommodates benzene, the most common ring in known drugs, and two positively charged fragments (methylguanidinium and 2-phenylimidazoline). the latter fragments were used as probes because of the large number of hydrogen bond accep ... | 2009 | 19572550 |
| detection of novel insect flavivirus sequences integrated in aedes albopictus (diptera: culicidae) in northern italy. | the presence of dna sequences integrated from a new flavivirus related to cell fusing agent and kamiti river virus was identified in wild aedes albopictus mosquito populations from the provinces of trentino and padova, northern italy. field work was developed during august-october 2007 with bg-traps, and mosquitoes were screened for flavivirus and alphavirus. no alphavirus was detected, indicating that chikungunya virus is not present in these mosquitoes in trentino and padova area. however, 21% ... | 2009 | 19575816 |
| longitudinal myelitis associated with yellow fever vaccination. | severe adverse reaction to yellow fever (yf) vaccine includes the yellow fever vaccine-associated neurotropic disease. this terminology includes postvaccinal encephalitis, acute disseminated encephalomyelitis, and guillain-barré syndrome. the objective of this communication is to report a patient who received a yf vaccine in argentina and subsequently developed longitudinal myelitis with a symptom that had previously gone unreported in the literature. a 56-year-old man began with progressive par ... | 2009 | 19579072 |
| isolation and characterization of a new insect flavivirus from aedes albopictus and aedes flavopictus mosquitoes in japan. | we isolated a new flavivirus from aedes albopictus mosquito and a related species in japan. the virus, designated aedes flavivirus (aefv), only replicated in a mosquito cell line and produced a mild cytopathic effect. the aefv genome was positive-sense, single-stranded rna, 11,064 nucleotides in length and contained a single open reading frame encoding a polyprotein of 3341 amino acids with 5' and 3' untranslated regions (utrs) of 96 and 945 nucleotides, respectively. genetic and phylogenetic an ... | 2009 | 19580982 |
| cellular inflammatory response to flaviviruses in the central nervous system of a primate host. | flaviviruses such as tick-borne encephalitis virus, japanese encephalitis virus, west nile virus, and st. louis encephalitis virus are important neurotropic human pathogens, typically causing a devastating and often fatal neuroinfection. flaviviruses induce neuroinflammation with typical features of viral encephalitides, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. development of safe and effective live-virus vaccines against neurotropic flaviviru ... | 2009 | 19581627 |
| nmr study of complexes between low molecular mass inhibitors and the west nile virus ns2b-ns3 protease. | the two-component ns2b-ns3 protease of west nile virus is essential for its replication and presents an attractive target for drug development. here, we describe protocols for the high-yield expression of stable isotope-labelled samples in vivo and in vitro. we also describe the use of nmr spectroscopy to determine the binding mode of new low molecular mass inhibitors of the west nile virus ns2b-ns3 protease which were discovered using high-throughput in vitro screening. binding to the substrate ... | 2009 | 19583774 |
| the immune adaptor molecule sarm modulates tumor necrosis factor alpha production and microglia activation in the brainstem and restricts west nile virus pathogenesis. | sterile alpha and heat/armadillo motif (sarm) is a highly conserved toll/interleukin-1 receptor (tir)-containing adaptor protein that is believed to negatively regulate signaling of the pathogen recognition receptors toll-like receptor 3 (tlr3) and tlr4. to test its physiological function in the context of a microbial infection, we generated sarm(-/-) mice and evaluated the impact of this deficiency on the pathogenesis of west nile virus (wnv), a neurotropic flavivirus that requires tlr signalin ... | 2009 | 19587044 |
| protein kinase g phosphorylates mosquito-borne flavivirus ns5. | serine/threonine phosphorylation of the nonstructural protein 5 (ns5) is a conserved feature of flaviviruses, but the kinase(s) responsible and function(s) remain unknown. mass spectrometry was used to compare the phosphorylation sites of the ns5 proteins of yellow fever virus (yfv) and dengue virus (denv), two flaviviruses transmitted by mosquitoes. seven denv phosphopeptides were identified, but only one conserved phosphoacceptor site (threonine 449 in denv) was identified in both viruses. thi ... | 2009 | 19587048 |
| selective involvement of temporal regions in a case of flavivirus encephalitis. | clinical manifestations of flavivirus infection may be various, from unapparent to severe meningoencephalitis. our patient, 2 weeks after returning home from a holiday at elba island, developed biphasic fever, later associated with nausea and vomiting and followed by incoming seizures responsive to thiopental sodium only. brain mri showed bilateral hyperintensity (t2) in amygdale, hippocampus, left insular and temporal inferior cortex. standard and microbiological csf examination was normal, but ... | 2009 | 19590822 |
| japanese encephalitis among three u.s. travelers returning from asia, 2003-2008. | japanese encephalitis virus (jev), a mosquito-borne flavivirus, is a leading cause of encephalitis in asia. the risk for japanese encephalitis (je) for most travelers is low, but varies by travel destination, duration, season, and activities. as part of routine surveillance and diagnostic testing, state health officials or clinicians send specimens from patients with unexplained encephalitis to cdc. to characterize the epidemiologic and clinical features of je cases, cdc reviewed all laboratory- ... | 2009 | 19609246 |
| prevalence of antibodies to west nile virus and other arboviruses among crested caracaras (caracara cheriway) in florida. | we documented the antibody prevalence to three arboviruses, st. louis encephalitis virus (slev), eastern equine encephalitis virus (eeev), and west nile virus (wnv), in crested caracaras (caracara cheriway; n = 80) in florida from 2007 to 2008. antibody prevalence to wnv was higher (9%) than for the other viruses. most seropositive birds were adults (< or =3 yr of age), with 55% of adults testing positive for antibodies to at least one virus. adults were significantly more likely to have antibod ... | 2009 | 19617494 |
| virus-host coevolution: common patterns of nucleotide motif usage in flaviviridae and their hosts. | virus-host biological interaction is a continuous coevolutionary process involving both host immune system and viral escape mechanisms. flaviviridae family is composed of fast evolving rna viruses that infects vertebrate (mammals and birds) and/or invertebrate (ticks and mosquitoes) organisms. these host groups are very distinct life forms separated by a long evolutionary time, so lineage-specific anti-viral mechanisms are likely to have evolved. flaviviridae viruses which infect a single host l ... | 2009 | 19617912 |
| structure of the methyltransferase domain from the modoc virus, a flavivirus with no known vector. | the modoc virus (modv) is a flavivirus with no known vector (nkv). evolutionary studies have shown that the viruses in the modv group have evolved in association with mammals (bats, rodents) without transmission by an arthropod vector. modv methyltransferase is the first enzyme from this evolutionary branch to be structurally characterized. the high-resolution structure of the methyltransferase domain of the modv ns5 protein (mtase(modv)) was determined. the protein structure was solved in the a ... | 2009 | 19622863 |
| expression of japanese encephalitis virus envelope protein in transgenic tobacco plants. | the virus envelope (e) protein of japanese encephalitis virus induces virus-neutralizing antibodies and is therefore a potential vaccine antigen. in a mammalian system, co-expression of another viral structural protein prm is necessary for proper expression and folding of e protein. transgenic tobacco plants were produced carrying jev cdna encoding prm and e proteins under the control of the camv 35s promoter. e protein, however, was not detectable in these plants. in vitro translation studies s ... | 2009 | 19628009 |
| understanding the molecular mechanism of blood-brain barrier damage in an experimental model of japanese encephalitis: correlation with minocycline administration as a therapeutic agent. | the blood-brain barrier (bbb) serves to protect the central nervous system (cns) from damage by exogenous molecules. japanese encephalitis (je), caused by a neurotropic flavivirus, leads to inflammation in the cns, neuronal death and also compromises the structural and functional integrity of the bbb. minocycline, a semisynthetic tetracycline, has been found to be broadly protective in neurological disease models featuring inflammation and cell death and at present, is being evaluated in clinica ... | 2009 | 19628016 |
| hepatitis c virus ns4b induces unfolded protein response and endoplasmic reticulum overload response-dependent nf-kappab activation. | hepatitis c virus nonstructural protein 4b (ns4b) is an endoplasmic reticulum (er) membrane associated protein and a potent causative factor of er stress. here we reported that unfolded protein response (upr) can be activated by hcv ns4b through inducing both xbp1 mrna splicing and atf6 cleavage in human hepatic cells. flow cytometric analysis revealed that hcv ns4b stimulates the production of reactive oxygen species (ros) by perturbing intracellular ca(2+) homeostasis. luciferase assay showed ... | 2009 | 19628242 |
| a membranotropic region in the c-terminal domain of hepatitis c virus protein ns4b interaction with membranes. | we have identified a membrane-active region in the hcv ns4b protein by studying membrane rupture induced by a ns4b-derived peptide library on model membranes. this segment corresponds to one of two previously predicted amphipathic helix and define it as a new membrane association domain. we report the binding and interaction with model membranes of a peptide patterned after this segment, peptide ns4b(h2), and show that ns4b(h2) strongly partitions into phospholipid membranes, interacts with them ... | 2010 | 19631190 |
| replivax wn, a single-cycle flavivirus vaccine to prevent west nile disease, elicits durable protective immunity in hamsters. | west nile virus (wnv) causes significant disease, yet no vaccines exist to prevent wn disease in humans. we have previously reported that replivax wn is a safe and efficacious vaccine in mouse and hamster models of wn disease. here, we report that vaccination of hamsters with replivax wn induces antibody responses that remain stable for at least 6 months. furthermore, animals challenged with virulent wnv 6 months after vaccination were protected from disease as well as those challenged 2 months ... | 2009 | 19635608 |
| nkp44 receptor mediates interaction of the envelope glycoproteins from the west nile and dengue viruses with nk cells. | dengue virus (dv) and west nile virus (wnv) have become a global concern due to their widespread distribution and their ability to cause a variety of human diseases. antiviral immune defenses involve nk cells. in the present study, we investigated the interaction between nk cells and these two flaviviruses. we show that the nk-activating receptor nkp44 is involved in virally mediated nk activation through direct interaction with the flavivirus envelope protein. recombinant nkp44 directly binds t ... | 2009 | 19635919 |
| the prm-independent packaging of pseudotyped japanese encephalitis virus. | as noted in other flaviviruses, the envelope (e) protein of japanese encephalitis virus (jev) interacts with a cellular receptor and mediates membrane fusion to allow viral entry into target cells, thus eliciting neutralizing antibody response. the formation of the flavivirus prm/e complex is followed by the cleavage of precursor membrane (prm) and membrane (m) protein by a cellular signalase. to test the effect of prm in jev biology, we constructed jev-mulv pseudotyped viruses that express the ... | 2009 | 19640312 |
| immunogenicity and protective efficacy of a recombinant subunit west nile virus vaccine in rhesus monkeys. | the immunogenicity and protective efficacy of a recombinant subunit west nile virus (wnv) vaccine was evaluated in rhesus macaques (macaca mulatta). the vaccine consisted of a recombinant envelope (e) protein truncated at the c-terminal end, resulting in a polypeptide containing 80% of the n-terminal amino acids of the native wnv protein (wn-80e), mixed with an adjuvant (gpi-0100). wn-80e was produced in a drosophila melanogaster expression system with high yield and purified by immunoaffinity c ... | 2009 | 19641099 |
| genomic sequence and phylogenetic analysis of culex flavivirus, an insect-specific flavivirus, isolated from culex pipiens (diptera: culicidae) in iowa. | adult mosquitoes (diptera: culicidae) were collected in 2007 and tested for specific viruses, including west nile virus, as part of the ongoing arbovirus surveillance efforts in the state of iowa. a subset of these mosquitoes (6,061 individuals in 340 pools) was further tested by reverse transcription-polymerase chain reaction (rt-pcr) using flavivirus universal primers. of the 211 pools of culex pipiens (l.) tested, 50 were positive. one of 51 pools of culex tarsalis coquillet was also positive ... | 2009 | 19645300 |
| effects of the number of amino acid residues in the signal segment upstream or downstream of the ns2b-3 cleavage site on production and secretion of prm/m-e virus-like particles of west nile virus. | expression of genes for precursor m (prm) and envelope (e) proteins of west nile virus (wnv) leads to the production of small, capsidless, and non-infectious virus-like particles (vlps) possessing the e antigen which is responsible for viral entry and immune protection. it has been reported that processing of the secretion signal affects viral release. we examined the secretion efficiency of vlps into the culture medium from rk13 or 293t cells transfected with expression vectors for prm and e pr ... | 2009 | 19647801 |
| [up-to-date knowledge of west nile virus infection]. | virus: west nile virus is a single-stranded rna virus of the family flaviviridae, genus flavivirus. | 2009 | 19650559 |
| identification of inhibitors of yellow fever virus replication using a replicon-based high-throughput assay. | flaviviruses cause severe disease in humans and are a public health priority worldwide. however, no effective therapies or drugs are commercially available yet. several flavivirus replicon-based assays amenable to high-throughput screening of inhibitors have been reported recently. we developed and performed a replicon-based high-throughput assay for screening small-molecule inhibitors of yellow fever virus (yfv) replication. this assay utilized packaged pseudoinfectious particles containing a y ... | 2009 | 19651907 |
| origin and distribution of tick-borne encephalitis virus strains of the siberian subtype in the middle urals, the north-west of russia and the baltic countries. | tick-borne encephalitis virus (tbev) plays an important role in infectious human morbidity, particularly in russia and the middle urals. the siberian subtype of tbev (s-tbev) is dominant in the middle urals. determining the origin of s-tbev strains in this territory and also in the european part of russia and the baltic countries is very important for understanding the cause of its distribution. the surface glycoprotein e gene was partially sequenced in 165 s-tbev isolates collected in the middl ... | 2009 | 19656959 |
| isolation of a novel species of flavivirus and a new strain of culex flavivirus (flaviviridae) from a natural mosquito population in uganda. | the genus flavivirus, which contains approximately 70 single-stranded, positive-sense rna viruses, represents a unique model for studying the evolution of vector-borne disease, as it includes viruses that are mosquito-borne, tick-borne or have no known vector. both theoretical work and field studies suggest the existence of a large number of undiscovered flaviviruses. recently, the first isolation of cell fusing agent virus (cfav) was reported from a natural mosquito population in puerto rico, a ... | 2009 | 19656970 |
| prevalence and genetic variability of tick-borne encephalitis virus in host-seeking ixodes ricinus in northern italy. | tick-borne encephalitis (tbe) is a severe disease that has been endemic in north-east italy since 1992. over the past two decades, there has been an increase in the number of human cases reported in many european countries, including italy. to assess the current tbe infection risk, questing ticks were collected from known tbe foci, as well as from a site in northern italy where no human infections have been reported previously. a total of 1739 ixodes ricinus (1485 nymphs and 254 adults) was coll ... | 2009 | 19675189 |
| molecular and serologic markers of acute dengue infection in naive and flavivirus-vaccinated travelers. | a total of 520 european travelers with suspected dengue fever were examined, and acute dengue virus infection was confirmed in 127 of them. molecular and serological tests for dengue diagnosis, according to their usefulness in the different stages of the disease, were performed. the accuracy of the igm/igg ratio and the igg avidity index was confirmed during the early phase of the illness to discriminate the serologic status (primary versus secondary immune response) of patients who were either ... | 2009 | 19679234 |
| extension of flavivirus protein c differentially affects early rna synthesis and growth in mammalian and arthropod host cells. | the translation of flaviviral rna genomes yields a single polyprotein that is processed into the mature proteins by viral and host cell proteases. mature capsid protein c is freed from the polyprotein by the viral ns2b/3 protease, cleaving in the c-terminal region of protein c in front of the signal sequence for prm. protein c has been shown to be involved in viral assembly and rna packaging. to examine further the role of protein c and its production by proteolysis, we replaced the ns2b/3 capsi ... | 2009 | 19692461 |
| a flavivirus protein m-derived peptide directly permeabilizes mitochondrial membranes, triggers cell death and reduces human tumor growth in nude mice. | dengue viruses belong to the flavivirus family and are responsible for hemorrhagic fever in human. dengue virus infection triggers apoptosis especially through the expression of the small membrane (m) protein. using isolated mitochondria, we found that synthetic peptides containing the c-terminus part of the m ectodomain caused apoptosis-related mitochondrial membrane permeabilization (mmp) events. these events include matrix swelling and the dissipation of the mitochondrial transmembrane potent ... | 2009 | 19693674 |
| mechanisms of evasion of the type i interferon antiviral response by flaviviruses. | virus survival and the ability to cause disease in mammalian hosts depend on their ability to avoid recognition and control by the interferon signal transduction and effector pathways. flaviviruses comprise a large family of nonsegmented positive sense enveloped cytoplasmic rna viruses, many of which are globally important human pathogens. although the mechanistic details are still being dissected, new insight has emerged as to how a flavivirus minimizes the antiviral activity of type i interfer ... | 2009 | 19694536 |
| safety evaluation of chimeric langat/dengue 4 flavivirus, a live vaccine candidate against tick-borne encephalitis. | the chimeric flavivirus lgt/den4 containing prm and e genes of naturally attenuated langat virus with remaining sequence derived from low neuroinvasive dengue 4 virus was previously produced and assessed as a candidate for live vaccine against tick-borne encephalitis (tbe) [pletnev and men (1998): proc natl acad sci usa 95:1746-1751; pletnev et al. (2000): virology 274:23-31; pletnev et al. (2001): j virol 75:8259-8267; wright et al. (2008): vaccine 26:882-890]. in this article we compared two a ... | 2009 | 19697399 |
| chapter 2. new insights into flavivirus nonstructural protein 5. | disease caused by flavivirus infections is an increasing world health problem. flavivirus nonstructural protein 5 (ns5) possesses enzymatic activities required for capping and synthesis of the viral rna genome and is essential for virus replication. ns5 is comprised of two domains. the n-terminal domain binds gtp and can perform two biochemically distinct methylation reactions required for rna cap formation. the c-terminal domain contains rna-dependent rna polymerase activity. as such, ns5 is an ... | 2009 | 19698895 |
| formation and function of hepatitis c virus replication complexes require residues in the carboxy-terminal domain of ns4b protein. | during replication, hepatitis c virus (hcv) ns4b protein rearranges intracellular membranes to form foci, or the web, the putative site for hcv replication. to understand the role of the c-terminal domain (ctd) in ns4b function, mutations were introduced into ns4b alone or in the context of hcv polyprotein. first, we show that the ctd is required for ns4b-induced web structure, but it is not sufficient to form the web nor is it required for ns4b membrane association. interestingly, all the mutat ... | 2009 | 19703698 |
| structure-activity relationship and improved hydrolytic stability of pyrazole derivatives that are allosteric inhibitors of west nile virus ns2b-ns3 proteinase. | west nile virus (wnv) is a potentially deadly mosquito-borne flavivirus which has spread rapidly throughout the world. currently there is no effective vaccine against flaviviral infections. we previously reported the identification of pyrazole ester derivatives as allosteric inhibitors of wnv ns2b-ns3 proteinase. these compounds degrade rapidly in ph 8 buffer with a half life of 1-2h. we now report the design, synthesis and in vitro evaluation of pyrazole derivatives that are inhibitors of wnv n ... | 2009 | 19703770 |
| tick-borne encephalitis virus infection of cultured mouse macrophages. | the interactions of tick-borne encephalitis virus (tbev) with mouse macrophages were studied at the electron microscopic level. the cultured mouse macrophages were sensitive to infection with tbev strain hypr (a highly neuroinvasive and neurovirulent strain for laboratory mice) and produced relatively high virus titers. however, these macrophage cells remained morphologically inactivated. viral particles were located mainly in the er but were also present in other exocytic compartments. no virus ... | 2009 | 19707021 |
| monoclonal antibodies to the west nile virus ns5 protein map to linear and conformational epitopes in the methyltransferase and polymerase domains. | the west nile virus (wnv) ns5 protein contains a methyltransferase (mtase) domain involved in rna capping and an rna-dependent rna polymerase (rdrp) domain essential for virus replication. crystal structures of individual wnv mtase and rdrp domains have been solved; however, the structure of full-length ns5 has not been determined. to gain more insight into the structure of ns5 and interactions between the mtase and rdrp domains, we generated a panel of seven monoclonal antibodies (mabs) to the ... | 2009 | 19710254 |
| influence of ns5a protein of classical swine fever virus (csfv) on csfv internal ribosome entry site-dependent translation. | an internal ribosome entry site (ires) present in the 5' untranslated region (utr) promotes translation of classical swine fever virus (csfv) genomes. using an in vitro system with monocistronic reporter rna containing the csfv 5'utr, this study found that csfv ns5a decreased csfv ires-mediated translation in a dose-dependent manner. deletion analysis showed that the region responsible for repressing csfv ires activity might cover aa 390-414, located in the c-terminal half of csfv ns5a. triple a ... | 2009 | 19710255 |
| specific interaction of capsid protein and importin-alpha/beta influences west nile virus production. | west nile virus (wnv) capsid (c) protein has been shown to enter the nucleus of infected cells. however, the mechanism by which c protein enters the nucleus is unknown. in this study, we have unveiled for the first time that nuclear transport of wnv and dengue virus c protein is mediated by their direct association with importin-alpha. this interplay is mediated by the consensus sequences of bipartite nuclear localization signal located between amino acid residues 85-101 together with amino acid ... | 2009 | 19712667 |
| structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibody. | flaviviruses are a group of human pathogens causing severe encephalitic or hemorrhagic diseases that include west nile, dengue and yellow fever viruses. here, using x-ray crystallography we have defined the structure of the flavivirus cross-reactive antibody e53 that engages the highly conserved fusion loop of the west nile virus envelope glycoprotein. using cryo-electron microscopy, we also determined that e53 fab binds preferentially to spikes in noninfectious, immature flavivirions but is una ... | 2009 | 19713934 |
| library screening by fragment-based docking. | we review our computational tools for high-throughput screening by fragment-based docking of large collections of small molecules. applications to six different enzymes, four proteases, and two protein kinases, are presented. remarkably, several low-micromolar inhibitors were discovered in each of the high-throughput docking campaigns. probable reasons for the lack of submicromolar inhibitors are the tiny fraction of chemical space covered by the libraries of available compounds, as well as the ... | 2010 | 19718684 |
| searching for west nile virus (wnv) in greece. | west nile virus (wnv), a mosquito-borne flavivirus, has increasingly become a concern in both america and europe due to its complex and unpredictable lifecycle. transfusion-associated transmission of the wnv has been well documented during the last few years. this study aimed to detect the presence of wnv in: (i) cerebrospinal fluid (csf) specimens derived from aseptic meningitis cases in greece and (ii) greek blood donations. a total of 115 csf specimens from patients suffering from aseptic men ... | 2010 | 19719473 |
| usutu virus in wild birds in northern italy. | usutu virus (usuv) infection was diagnosed in two free-living blackbirds and in three captive owls belonging to two different species in northern italy in the summers of 2006-2008. diagnosis was established by immunohistochemistry and rt-pcr. rt-pcr was performed on frozen and on paraffin-embedded tissues (pet), respectively. from the frozen samples a partial sequence of the putative usuv e and ns1 proteins (1229 bp) was determined, whereas partial sequences of the putative ns3 (278 bp) and ns5 ... | 2010 | 19720475 |
| generating flavivirus vaccine candidates by modulating interferon sensitivity. | | 2009 | 19722889 |
| [dengue fever: from disease to vaccination]. | dengue is a tropical disease affecting 110 countries throughout the world and placing over 3 billion people at risk of infection. according the world health organization 70 to 500 million persons are infected every year including 2 million who develop hemorrhagic form and 20,000 who die. children are at highest risk for death. due to the absence of specialized laboratories in most endemic regions and to the lack of specifici clinical presentation, the incidence of dengue and its economic costs a ... | 2009 | 19725380 |
| [dengue and other arboviral diseases in south-east asia]. | the most medically significant arboviruses causing human illness in south-east asia belong to the genera flavivirus (dengue, japanese encephalitis, kunjin, zika, etc.) and alphavirus (chikungunya, sindbis, getah, etc.). all of these arboviral diseases are transmitted by mosquitoes. dengue virus is the most prevalent arbovirus in south-east asia and constitutes a major public health problem. japanese encephalitis virus is also widespread in the region and symptomatic infection is associated with ... | 2009 | 19725383 |
| exclusion of west nile virus superinfection through rna replication. | superinfection exclusion is the ability of an established viral infection to interfere with a second viral infection. using west nile virus (wnv) as a model, we show that replicating replicons in bhk-21 cells suppress subsequent wnv infection. the wnv replicon also suppresses superinfections of other flaviviruses but not nonflaviviruses. mode-of-action analysis indicates that the exclusion of wnv superinfection occurs at the step of rna synthesis. the continuous culturing of wnv in the replicon- ... | 2009 | 19726510 |
| optimization of assay conditions for dengue virus protease: effect of various polyols and nonionic detergents. | the aim of this work was to perform a systematic study of the effect of nonionic detergents on the activity of the dengue virus ns2b-ns3 protease. to ensure a high activity of the protease, the assay procedures for the dengue virus and other flaviviral proteases published to date are performed in the presence of up to 35% glycerol, which does not represent the cellular physicochemical environment. in addition, the high viscosity of glycerol-containing solutions leads to various experimental prob ... | 2009 | 19726784 |
| 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 |
| genomics and evolution of aedes-borne flaviviruses. | we analysed the complete coding sequences of all recognized species of aedes-borne flavivirus, including previously uncharacterized viruses within the yellow fever virus (yfv), spondweni virus (spov) and dengue virus (denv) groups. two major phylogenetic lineages were revealed: one included the yfv and entebbe bat virus groups, and the other included the denv, spov and culex-borne flavivirus groups. this analysis supported previous evidence that culex-borne flaviviruses have evolved from ancestr ... | 2010 | 19741066 |
| complement modulates pathogenesis and antibody-dependent neutralization of west nile virus infection through a c5-independent mechanism. | although the interactions of complement and viruses have been widely studied, the function of c5 and the membrane attack complex in the context of viral infection or antibody-mediated neutralization remains controversial. using c5-depleted or -deficient human or mouse sera, we show that c5 does not contribute to the antibody-dependent or -independent neutralization of west nile virus (wnv) in cell culture. consistent with this, c5 neither contributed to protection against wnv pathogenesis nor au ... | 2009 | 19744691 |
| [west nile fever]. | west nile fever is a mosquito-borne febrile illness seen in africa, asia, and europe, but reported in north america only once. west nile virus is of the family flaviviridae, genus flavivirus. several west nile fever outbreaks were reported from israel in the 1950s and in 1980. since the mid-1990s, frequency and apparent clinical severity of west nile virus outbreaks have increased. outbreaks in rumania (1996), russia (1999), and israel (2000) involved hundreds of persons with severe neurologic d ... | 2003 | 19753724 |
| 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 |
| association of the pr peptides with dengue virus at acidic ph blocks membrane fusion. | flavivirus assembles into an inert particle that requires proteolytic activation by furin to enable transmission to other hosts. we previously showed that immature virus undergoes a conformational change at low ph that renders it accessible to furin (i. m. yu, w. zhang, h. a. holdaway, l. li, v. a. kostyuchenko, p. r. chipman, r. j. kuhn, m. g. rossmann, and j. chen, science 319:1834-1837, 2008). here we show, using cryoelectron microscopy, that the structure of immature dengue virus at ph 6.0 i ... | 2009 | 19759134 |
| predicted rna secondary structures for the conserved regions in dengue virus. | dengue fever, dengue hemorrhagic fever and dengue shock syndrome are the prevalent mosquito borne viral infections worldwide. the dengue virus belongs to the genus flavivirus with conserved rna domains peptidase_s7 and dexhc among its members. the secondary structures for rna domains peptidase_s7 and dexhc are hence predicted and discussed with other known viral rna structures to glean structural insights through comparison. | 2009 | 19759866 |
| zoonotic mosquito-borne flaviviruses: worldwide presence of agents with proven pathogenicity and potential candidates of future emerging diseases. | an update on the mosquito-borne flavivirus species including certain subtypes, as listed in the eighth report of the international committee on taxonomy of viruses, is given. special emphasis is placed on viruses which have been shown to cause diseases in animals, and viruses for which no pathogenicity has been proven yet. several recent examples (usutu virus and lineage-2 west nile virus in central europe, zika virus in micronesia) have shown that sources providing information on such scientifi ... | 2010 | 19762169 |
| bacterial cell surface display: a method for studying japanese encephalitis virus pathogenicity. | infection with japanese encephalitis virus (jev), a mosquito-borne, neurotropic flavivirus, may cause acute encephalitis in humans. recombinant salmonella typhimurium brd509 was constructed to display domain iii of the envelope (e) protein of jev (jediii) on its surface with the n-terminal domain of ice nucleation protein (inpn) as the display motif. bacterial cell surface display was confirmed by western blot analysis and immunohistochemical staining. binding of recombinant inpn-jediii and jedi ... | 2009 | 19762996 |
| zoonotic tick-borne flaviviruses. | tick-borne flaviviruses are among the medically most important arboviruses in europe and asia. tick-borne encephalitis causes between 10,000 and 15,000 human cases every year in both continents. besides this disease there are several other tick-borne flaviviruses which may be of local medical importance, and which are less known, but may be important as differential diagnosis. among them are louping-ill disease which is present mainly on the british islands, omsk hemorrhagic fever, which is prev ... | 2010 | 19765917 |
| experimental evidence that rna recombination occurs in the japanese encephalitis virus. | due to the lack of a proofreading function and error-repairing ability of genomic rna, accumulated mutations are known to be a force driving viral evolution in the genus flavivirus, including the japanese encephalitis (je) virus. based on sequencing data, rna recombination was recently postulated to be another factor associated with genomic variations in these viruses. we herein provide experimental evidence to demonstrate the occurrence of rna recombination in the je virus using two local pure ... | 2009 | 19766282 |
| protonation of individual histidine residues is not required for the ph-dependent entry of west nile virus: evaluation of the "histidine switch" hypothesis. | histidine residues have been hypothesized to function as sensors of environmental ph that can trigger the activity of viral fusion proteins. we investigated a requirement for histidine residues in the envelope (e) protein of west nile virus during ph-dependent entry into cells. each histidine was individually replaced with a nonionizable amino acid and tested functionally. in each instance, mutants capable of orchestrating ph-dependent infection were identified. these results do not support a re ... | 2009 | 19776132 |
| biochemical characterization of the (nucleoside-2'o)-methyltransferase activity of dengue virus protein ns5 using purified capped rna oligonucleotides (7me)gpppac(n) and gpppac(n). | the flavivirus rna genome contains a conserved cap-1 structure, (7me)gpppa(2'ome)g, at the 5' end. two mrna cap methyltransferase (mtase) activities involved in the formation of the cap, the (guanine-n7)- and the (nucleoside-2'o)-mtases (2'o-mtase), reside in a single domain of non-structural protein ns5 (ns5mtase). this study reports on the biochemical characterization of the 2'o-mtase activity of ns5mtase of dengue virus (ns5mtase(dv)) using purified, short, capped rna substrates ((7me)gpppac( ... | 2010 | 19776234 |
| in silico screening of small molecule libraries using the dengue virus envelope e protein has identified compounds with antiviral activity against multiple flaviviruses. | the flaviviruses comprise a large group of related viruses, many of which pose a significant global human health threat, most notably the dengue viruses (denv), west nile virus (wnv) and yellow fever virus (yfv). flaviviruses enter host cells via fusion of the viral and cellular membranes, a process mediated by the major viral envelope protein e as it undergoes a low ph induced conformational change in the endosomal compartment of the host cell. this essential entry stage in the flavivirus life ... | 2009 | 19781577 |
| cis-acting rna elements in human and animal plus-strand rna viruses. | the rna genomes of plus-strand rna viruses have the ability to form secondary and higher-order structures that contribute to their stability and to their participation in inter- and intramolecular interactions. those structures that are functionally important are called cis-acting rna elements because their functions cannot be complemented in trans. they can be involved not only in rna/rna interactions but also in binding of viral and cellular proteins during the complex processes of translation ... | 2009 | 19781674 |
| highly permissive infection of microglial cells by japanese encephalitis virus: a possible role as a viral reservoir. | japanese encephalitis virus (jev), a mosquito-borne flavivirus, is a major cause of acute encephalitis, and neurons have been proposed to be the principle jev target cells in the central nervous system. however, clinically, infection with jev leads to increased levels of cytokines and chemokines in the serum and cerebrospinal fluid (csf) the levels of which correlate with the mortality rate of patients. this research aimed to study the role of microglial cells in jev infection. mouse microglial ... | 2010 | 19786116 |
| detection by elisa of antibodies to japanese encephalitis virus nonstructural 1 protein induced in subclinically infected humans. | japanese encephalitis (je) is a fatal mosquito-borne disease that is vaccine-preventable. the natural infection rate is a critical factor for evaluations of the necessity for vaccination. detection of antibodies to virus nonstructural (ns) proteins is a theoretical strategy to survey natural infections among populations vaccinated with an inactivated je vaccine consisting of only structural proteins. here, we present our development of an enzyme-linked immunosorbent assay (elisa) to detect low l ... | 2009 | 19786140 |
| zika virus outside africa. | zika virus (zikv) is a flavivirus related to yellow fever, dengue, west nile, and japanese encephalitis viruses. in 2007 zikv caused an outbreak of relatively mild disease characterized by rash, arthralgia, and conjunctivitis on yap island in the southwestern pacific ocean. this was the first time that zikv was detected outside of africa and asia. the history, transmission dynamics, virology, and clinical manifestations of zikv disease are discussed, along with the possibility for diagnostic con ... | 2009 | 19788800 |
| characteristics of antibody responses in tick-borne encephalitis vaccination breakthroughs. | tick-borne encephalitis (tbe) virus is an important human pathogenic flavivirus that is endemic in europe and asia. the disease can be effectively prevented by inactivated vaccines and vaccination breakthroughs (vbts) are rare. we investigated the characteristics of antibody responses in such vbts in comparison to those in unvaccinated tbe patients. in contrast to the unvaccinated controls, most of the vbts displayed a delayed igm antibody response and had high avidity and strongly neutralizing ... | 2009 | 19789092 |
| crystal structure of a novel conformational state of the flavivirus ns3 protein: implications for polyprotein processing and viral replication. | the flavivirus genome comprises a single strand of positive-sense rna, which is translated into a polyprotein and cleaved by a combination of viral and host proteases to yield functional proteins. one of these, nonstructural protein 3 (ns3), is an enzyme with both serine protease and ntpase/helicase activities. ns3 plays a central role in the flavivirus life cycle: the ns3 n-terminal serine protease together with its essential cofactor ns2b is involved in the processing of the polyprotein, where ... | 2009 | 19793813 |
| dealing with low ph: entry and exit of alphaviruses and flaviviruses. | the alphaviruses and flaviviruses include many important human pathogens, such as the dengue, west nile, and chikungunya viruses. these enveloped viruses infect cells by a membrane fusion reaction triggered by the low ph in endosomes. fusion is mediated by viral membrane proteins through their acid-dependent conversion from a dimer on the virus surface to a homotrimer inserted into the host cell membrane. here we review recent studies on the regulatory mechanisms that silence these fusion protei ... | 2009 | 19796949 |
| 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 |
| immunogenicity of sanofi pasteur tetravalent dengue vaccine. | a candidate tetravalent (tv) dengue vaccine based on the yellow fever (yf) 17d vaccine has been developed by sanofi pasteur. this dengue tv vaccine induced a controlled dendritic cell stimulation in vitro. in clinical trials, th1 and cd8 responses were induced with an ifn-gamma/tnf-alpha ratio favouring ifn-gamma in both cases, regardless of whether the vaccine recipients were flavivirus naive or not. there was an absence of th2 response in all cases. the th1 response was dominated by the d4 ser ... | 2009 | 19800561 |
| recent progress on sanofi pasteur's dengue vaccine candidate. | the sanofi pasteur candidate dengue tetravalent vaccine (tv) is a recombinant live attenuated vaccine. it is based on a backbone of yellow fever vaccine (yf 17d) replication genes and incorporates the envelope genes of the four dengue virus serotypes. pre-clinical studies have demonstrated that dengue tv is genetically stable, non-hepatotropic, less neurovirulent than yf 17d and does not infect mosquitoes by the oral route. dengue tv reactogenicity, viraemia induction and antibody responses were ... | 2009 | 19800562 |
| guidelines for clinical trials of dengue vaccine in endemic areas. | guidelines for the clinical evaluation of dengue vaccines in endemic areas have recently been developed, building upon earlier recommendations published in 2002 (who. 2002. guidelines for the evaluation of dengue vaccines in populations exposed to natural infection. geneva, switzerland. report no. tdr/ivr/den/02.1). this new document discusses the rationale and background of dengue vaccine trials and outlines dengue case definitions, proposed efficacy end points, requirements for trial sites, me ... | 2009 | 19800564 |
| non-hemagglutinating flaviviruses: molecular mechanisms for the emergence of new strains via adaptation to european ticks. | tick-borne encephalitis virus (tbev) causes human epidemics across eurasia. clinical manifestations range from inapparent infections and fevers to fatal encephalitis but the factors that determine disease severity are currently undefined. tbev is characteristically a hemagglutinating (ha) virus; the ability to agglutinate erythrocytes tentatively reflects virion receptor/fusion activity. however, for the past few years many atypical ha-deficient strains have been isolated from patients and also ... | 2009 | 19802385 |
| preclinical and clinical development of yfv 17d-based chimeric vaccines against dengue, west nile and japanese encephalitis viruses. | dengue viruses (denv), west nile virus (wnv) and japanese encephalitis virus (jev) are major global health and growing medical problems. while a live-attenuated vaccine exists since decades against the prototype flavivirus, yellow fever virus (yfv), there is an urgent need for vaccines against dengue or west nile diseases, and for improved vaccines against japanese encephalitis. live-attenuated chimeric viruses were constructed by replacing the genes coding for premembrane (prm) and envelope (e) ... | 2010 | 19808029 |
| il-10 signaling blockade controls murine west nile virus infection. | west nile virus (wnv), a mosquito-borne single-stranded rna flavivirus, can cause significant human morbidity and mortality. our data show that interleukin-10 (il-10) is dramatically elevated both in vitro and in vivo following wnv infection. consistent with an etiologic role of il-10 in wnv pathogenesis, we find that wnv infection is markedly diminished in il-10 deficient (il-10(-/-)) mice, and pharmacologic blockade of il-10 signaling by il-10 neutralizing antibody increases survival of wnv-in ... | 2009 | 19816558 |
| recombination in west nile virus: minimal contribution to genomic diversity. | recombination is known to play a role in the ability of various viruses to acquire sequence diversity. we consequently examined all available west nile virus (wnv) whole genome sequences both phylogenetically and with a variety of computational recombination detection algorithms. we found that the number of distinct lineages present on a phylogenetic tree reconstruction to be identical to the 6 previously reported. statistically-significant evidence for recombination was only observed in one who ... | 2009 | 19821990 |
| 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 |
| characterization of west nile virus isolates from spain: new insights into the distinct west nile virus eco-epidemiology in the western mediterranean. | west nile virus (wnv) is a mosquito-borne flavivirus which causes important morbidity and mortality in birds, horses and humans. in the western mediterranean region, wnv causes sporadic, self-limited outbreaks, with few or no human cases. here we report the characterization of two recent western mediterranean wnv isolates, obtained in spain in 2007 from two golden eagles. complete genome sequence comparisons revealed high identity between these isolates and close relationship with other western ... | 2009 | 19833373 |