Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| a conserved motif in region v of the large polymerase proteins of nonsegmented negative-sense rna viruses that is essential for mrna capping. | nonsegmented negative-sense (nns) rna viruses cap their mrna by an unconventional mechanism. specifically, 5' monophosphate mrna is transferred to gdp derived from gtp through a reaction that involves a covalent intermediate between the large polymerase protein l and mrna. this polyribonucleotidyltransferase activity contrasts with all other capping reactions, which are catalyzed by an rna triphosphatase and guanylyltransferase. in these reactions, a 5' diphosphate mrna is capped by transfer of ... | 2008 | 18003731 |
| replication-coupled packaging mechanism in positive-strand rna viruses: synchronized coexpression of functional multigenome rna components of an animal and a plant virus in nicotiana benthamiana cells by agroinfiltration. | flock house virus (fhv), a bipartite rna virus of insects and a member of the nodaviridae family, shares viral replication features with the tripartite brome mosaic virus (bmv), an rna virus that infects plants and is a member of the bromoviridae family. in bmv and fhv, genome packaging is coupled to replication, a widely conserved mechanism among positive-strand rna viruses of diverse origin. to unravel the events that modulate the mechanism of replication-coupled packaging, in this study, we h ... | 2008 | 18032497 |
| complement and its role in protection and pathogenesis of flavivirus infections. | the complement system is a family of serum and cell surface proteins that recognize pathogen-associated molecular patterns, altered-self ligands, and immune complexes. activation of the complement cascade triggers several antiviral functions including pathogen opsonization and/or lysis, and priming of adaptive immune responses. in this review, we will examine the role of complement activation in protection and/or pathogenesis against infection by flaviviruses, with an emphasis on experiments wit ... | 2008 | 19388173 |
| crystal structure of the ns3 protease-helicase from dengue virus. | several flaviviruses are important human pathogens, including dengue virus, a disease against which neither a vaccine nor specific antiviral therapies currently exist. during infection, the flavivirus rna genome is translated into a polyprotein, which is cleaved into several components. nonstructural protein 3 (ns3) carries out enzymatic reactions essential for viral replication, including proteolysis of the polyprotein through its serine protease n-terminal domain, with a segment of 40 residues ... | 2008 | 17942558 |
| characterization of hepatitis c rna-containing particles from human liver by density and size. | hepatitis c virus (hcv) particles found in vivo are heterogeneous in density and size, but their detailed characterization has been restricted by the low titre of hcv in human serum. previously, our group has found that hcv circulates in blood in association with very-low-density lipoprotein (vldl). our aim in this study was to characterize hcv rna-containing membranes and particles in human liver by both density and size and to identify the subcellular compartment(s) where the association with ... | 2008 | 18796720 |
| sars-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum. | positive-strand rna viruses, a large group including human pathogens such as sars-coronavirus (sars-cov), replicate in the cytoplasm of infected host cells. their replication complexes are commonly associated with modified host cell membranes. membrane structures supporting viral rna synthesis range from distinct spherular membrane invaginations to more elaborate webs of packed membranes and vesicles. generally, their ultrastructure, morphogenesis, and exact role in viral replication remain to b ... | 2008 | 18798692 |
| co-selection of west nile virus nucleotides that confer resistance to an antisense oligomer while maintaining long-distance rna/rna base pairings. | west nile virus (wnv) genome cyclization is mediated by two pairs of long-distance rna/rna interactions: the 5'cs/3'csi (conserved sequence) and the 5'uar/3'uar (upstream aug region) base pairings. antisense peptide-conjugated phosphorodiamidate morpholino oligomers (ppmos), designed to interfere with the 5'cs/3'csi or 5'uar/3'uar base pairings, were previously shown to inhibit wnv. in this study, we selected and characterized wnvs resistant to a ppmo targeting the 3'uar (3'uar-ppmo). all resist ... | 2008 | 18842280 |
| vector competence of australian mosquito species for a north american strain of west nile virus. | since the establishment of west nile virus (wnv) into the united states, concern has arisen that this virus may also pose a serious threat to australian biosecurity. the vector competence of 19 australian mosquito species for a north american strain of wnv was evaluated. mosquitoes collected from cairns, brisbane, and sydney were exposed to blood containing 10(4.0+/-0.3) cell culture infectious dose(50)/mosquito wnv that was isolated from a crow during the 1999 new york outbreak. mosquitoes were ... | 2008 | 18973445 |
| dissecting the cell entry pathway of dengue virus by single-particle tracking in living cells. | dengue virus (denv) is an enveloped rna virus that causes the most common arthropod-borne infection worldwide. the mechanism by which denv infects the host cell remains unclear. in this work, we used live-cell imaging and single-virus tracking to investigate the cell entry, endocytic trafficking, and fusion behavior of denv. simultaneous tracking of denv particles and various endocytic markers revealed that denv enters cells exclusively via clathrin-mediated endocytosis. the virus particles move ... | 2008 | 19096510 |
| visualization of double-stranded rna in cells supporting hepatitis c virus rna replication. | the mechanisms involved in hepatitis c virus (hcv) rna replication are unknown, and this aspect of the virus life cycle is not understood. it is thought that virus-encoded nonstructural proteins and rna genomes interact on rearranged endoplasmic reticulum (er) membranes to form replication complexes, which are believed to be sites of rna synthesis. we report that, through the use of an antibody specific for double-stranded rna (dsrna), dsrna is readily detectable in huh-7 cells that contain repl ... | 2008 | 18094154 |
| functional analysis of potential carboxy-terminal cleavage sites of tick-borne encephalitis virus capsid protein. | the mature capsid protein c of flaviviruses is generated through the proteolytic cleavage of the precursor polyprotein by the viral ns2b/3 protease. this cleavage is a prerequisite for the subsequent processing of the viral surface protein prm, and the concerted progression of these events plays a key role in the process of the assembly of infectious virions. protein c of tick-borne encephalitis virus (tbev) contains two amino acid sequence motifs within the carboxy-terminal region that match th ... | 2008 | 18160443 |
| yellow fever virus ns3 plays an essential role in virus assembly independent of its known enzymatic functions. | in flaviviruses it has been proposed that there is a coupling between genome replication and virion assembly and that nonstructural proteins are involved in this process. it was previously reported that mutations in yellow fever virus (yfv) nonstructural protein ns2a blocked production of infectious virus and that this block could be released by a suppressor mutation in ns3. here, based on studies using a yfv replicon-based trans-packaging system as well as full-length yfv cdna, we report that m ... | 2008 | 18199634 |
| defining the levels of secreted non-structural protein ns1 after west nile virus infection in cell culture and mice. | infection with west nile virus (wnv) causes a febrile illness that can progress to meningitis or encephalitis, primarily in humans that are immunocompromised or elderly. for successful treatment of wnv infection, accurate and timely diagnosis is essential. previous studies have suggested that the flavivirus non-structural protein ns1, a highly conserved and secreted glycoprotein, is a candidate protein for rapid diagnosis. herein, we developed a capture enzyme-linked immunosorbent assay (elisa) ... | 2008 | 18205232 |
| universal primers that amplify rna from all three flavivirus subgroups. | species within the flavivirus genus pose public health problems around the world. increasing cases of dengue and japanese encephalitis virus in asia, frequent outbreaks of yellow fever virus in africa and south america, and the ongoing spread of west nile virus throughout the americas, show the geographical burden of flavivirus diseases. flavivirus infections are often indistinct from and confused with other febrile illnesses. here we review the specificity of published primers, and describe a n ... | 2008 | 18218114 |
| genetic determinants of virulence in pathogenic lineage 2 west nile virus strains. | we determined complete genome sequences of lineage 2 west nile virus (wnv) strains isolated from patients in south africa who had mild or severe wnv infections. these strains had previously been shown to produce either highly or less neuroinvasive infection and induced genes similar to corresponding highly or less neuroinvasive lineage 1 strains in mice. phylogenetic and amino acid comparison of highly and less neuroinvasive lineage 2 strains demonstrated that the nonstructural genes, especially ... | 2008 | 18258114 |
| formation of the arterivirus replication/transcription complex: a key role for nonstructural protein 3 in the remodeling of intracellular membranes. | the replication/transcription complex of the arterivirus equine arteritis virus (eav) is associated with paired membranes and/or double-membrane vesicles (dmvs) that are thought to originate from the endoplasmic reticulum. previously, coexpression of two putative transmembrane nonstructural proteins (nsp2 and nsp3) was found to suffice to induce these remarkable membrane structures, which are typical of arterivirus infection. here, site-directed mutagenesis was used to investigate the role of ns ... | 2008 | 18305048 |
| genetic variability of west nile virus in us blood donors, 2002-2005. | west nile virus (wnv) was detected in the united states in 1999, has reoccurred every summer since, and has become endemic. transfusion transmission was documented in 2002, and screening of blood donations for wnv began in 2003. we investigated genetic variation of wnv in human isolates obtained from specimens collected from 30 infected blood donors who tested positive for wnv rna during 2002-2005. complete genomic sequences of 8 isolates and structural gene sequences from 22 additional isolates ... | 2008 | 18325259 |
| role of nonstructural protein ns2a in flavivirus assembly. | flavivirus nonstructural (ns) proteins are involved in rna replication and modulation of the host antiviral response; however, evidence is mounting that some ns proteins also have essential roles in virus assembly. kunjin virus (kun) ns2a is a small, hydrophobic, transmembrane protein that is part of the replication complex and inhibits interferon induction. previously, we have shown that an isoleucine (i)-to-asparagine (n) substitution at position 59 of the ns2a protein blocked the production o ... | 2008 | 18337583 |
| the relative contribution of antibody and cd8+ t cells to vaccine immunity against west nile encephalitis virus. | west nile virus (wnv) is a mosquito borne, neurotropic flavivirus that causes a severe central nervous system (cns) infection in humans and animals. although commercial vaccines are available for horses, none is currently approved for human use. in this study, we evaluated the efficacy and mechanism of immune protection of two candidate wnv vaccines in mice. a formalin-inactivated wnv vaccine induced higher levels of specific and neutralizing antibodies compared to a dna plasmid vaccine that pro ... | 2008 | 18339459 |
| antigen-specific immunotherapy of cervical and ovarian cancer. | we contrast the efforts to treat ovarian cancer and cervical cancer through vaccination because of their different pathobiology. a plethora of approaches have been developed for therapeutic vaccination against cancer, many of which target defined tumor-associated antigens (taas). persistent infection with oncogenic human papillomavirus (hpv) types causes cervical cancer. furthermore, cervical cancer patients frequently mount both humoral and t-cell immune responses to the hpv e6 and e7 oncoprote ... | 2008 | 18363994 |
| west nile virus entry requires cholesterol-rich membrane microdomains and is independent of alphavbeta3 integrin. | west nile virus (wnv) has been the leading cause of viral encephalitis in the united states since 1999. the endocytic processes involved in the internalization of infectious wnv by various cell types are not well characterized, and the involvement of cholesterol-rich membrane microdomains, or lipid rafts, in the life cycle of wnv has not been investigated previously. in this study, we found that the depletion of cellular cholesterol levels by brief treatment with methyl-beta-cyclodextrin resulte ... | 2008 | 18385233 |
| the two-component ns2b-ns3 proteinase represses dna unwinding activity of the west nile virus ns3 helicase. | similar to many flavivirus types including dengue and yellow fever viruses, the nonstructural ns3 multifunctional protein of west nile virus (wnv) with an n-terminal serine proteinase domain and an rna triphosphatase, an ntpase domain, and an rna helicase in the c-terminal domain is implicated in both polyprotein processing and rna replication and is therefore a promising drug target. to exhibit its proteolytic activity, ns3 proteinase requires the presence of the cofactor encoded by the upstrea ... | 2008 | 18442976 |
| maturation of west nile virus modulates sensitivity to antibody-mediated neutralization. | west nile virions incorporate 180 envelope (e) proteins that orchestrate the process of virus entry and are the primary target of neutralizing antibodies. the e proteins of newly synthesized west nile virus (wnv) are organized into trimeric spikes composed of pre-membrane (prm) and e protein heterodimers. during egress, immature virions undergo a protease-mediated cleavage of prm that results in a reorganization of e protein into the pseudo-icosahedral arrangement characteristic of mature virion ... | 2008 | 18464894 |
| molecular mechanisms of antibody-mediated neutralisation of flavivirus infection. | flaviviruses are a group of positive-stranded rna viruses that cause a spectrum of severe illnesses globally in more than 50 million individuals each year. while effective vaccines exist for three members of this group (yellow fever, japanese encephalitis, and tick-borne encephalitis viruses), safe and effective vaccines for several other flaviviruses of clinical importance, including west nile and dengue viruses, remain in development. an effective humoral immune response is critical for protec ... | 2008 | 18471342 |
| humanized monoclonal antibodies derived from chimpanzee fabs protect against japanese encephalitis virus in vitro and in vivo. | japanese encephalitis virus (jev)-specific fab antibodies were recovered by repertoire cloning from chimpanzees initially immunized with inactivated je-vax and then boosted with attenuated jev sa14-14-2. from a panel of 11 fabs recovered by different panning strategies, three highly potent neutralizing antibodies, termed fabs a3, b2, and e3, which recognized spatially separated regions on the virion, were identified. these antibodies reacted with epitopes in different domains: the major determin ... | 2008 | 18480437 |
| efficient trans-encapsidation of hepatitis c virus rnas into infectious virus-like particles. | recently, complete replication of hepatitis c virus (hcv) in tissue culture was established using the jfh1 isolate. to analyze determinants of hcv genome packaging and virion assembly, we developed a system that supports particle production based on trans-packaging of subgenomic viral rnas. using jfh1 helper viruses, we show that subgenomic jfh1 replicons lacking the entire core to ns2 coding region are efficiently encapsidated into infectious virus-like particles. similarly, chimeric helper vir ... | 2008 | 18480457 |
| west nile virus infection of drosophila melanogaster induces a protective rnai response. | to determine if west nile virus (wnv) infection of insect cells induces a protective rnai response, drosophila melanogaster s2 and aedes albopictus c6/36 cells were infected with wnv, and the production of wnv-homologous small rnas was assayed as an indicator of rnai induction. a distinct population of approximately 25 nt wnv-homologous small rnas was detected in infected s2 cells but not c6/36 cells. rnai knockdown of argonaute 2 in s2 cells resulted in slightly increased susceptibility to wnv ... | 2008 | 18501400 |
| ires-dependent replication of venezuelan equine encephalitis virus makes it highly attenuated and incapable of replicating in mosquito cells. | the development of infectious cdna for different alphaviruses opened an opportunity to explore their attenuation by extensively modifying the viral genomes, an approach that might minimize or exclude the reversion to the wild-type, pathogenic phenotype. moreover, the genomes of such alphaviruses can be engineered to contain rna elements that would be functional only in cells of vertebrate, but not insect, origin. in the present study, we developed a recombinant veev that is more attenuated than ... | 2008 | 18501401 |
| separate molecules of west nile virus methyltransferase can independently catalyze the n7 and 2'-o methylations of viral rna cap. | west nile virus methyltransferase catalyzes n7 and 2'-o methylations of the viral rna cap (gpppa-rna-->m(7)gpppam-rna). the two methylation events are independent, as evidenced by efficient n7 methylation of gpppa-rna-->m(7)gpppa-rna and gpppam-rna-->m(7)gpppam-rna, and by the 2'-o methylation of gpppa-rna-->gpppam-rna and m(7)gpppa-rna-->m(7)gpppam-rna. however, the 2'-o methylation activity prefers substrate m(7)gpppa-rna to gpppa-rna, thereby determining the dominant methylation pathway as gp ... | 2008 | 18501946 |
| ns3 helicase domains involved in infectious intracellular hepatitis c virus particle assembly. | a mutation within subdomain 1 of the hepatitis c virus (hcv) ns3 helicase (ns3-q221l) (m. yi, y. ma, j. yates, and s. m. lemon, j. virol. 81:629-638, 2007) rescues a defect in production of infectious virus by an intergenotypic chimeric rna (hj3). although ns3-gln-221 is highly conserved across hcv genotypes, the leu-221 substitution had no effect on rna replication or ns3-associated enzymatic activities. however, while transfection of unmodified hj3 rna failed to produce either extracellular or ... | 2008 | 18508894 |
| a single n-linked glycosylation site in the japanese encephalitis virus prm protein is critical for cell type-specific prm protein biogenesis, virus particle release, and pathogenicity in mice. | the prm protein of japanese encephalitis virus (jev) contains a single potential n-linked glycosylation site, n(15)-x(16)-t(17), which is highly conserved among jev strains and closely related flaviviruses. to investigate the role of this site in jev replication and pathogenesis, we manipulated the rna genome by using infectious jev cdna to generate three prm mutants (n15a, t17a, and n15a/t17a) with alanine substituting for n(15) and/or t(17) and one mutant with silent point mutations introduced ... | 2008 | 18524814 |
| interaction of hepatitis c virus nonstructural protein 5a with core protein is critical for the production of infectious virus particles. | nonstructural protein 5a (ns5a) of the hepatitis c virus (hcv) possesses multiple and diverse functions in rna replication, interferon resistance, and viral pathogenesis. recent studies suggest that ns5a is involved in the assembly and maturation of infectious viral particles; however, precisely how ns5a participates in virus production has not been fully elucidated. in the present study, we demonstrate that ns5a is a prerequisite for hcv particle production as a result of its interaction with t ... | 2008 | 18524832 |
| association of hepatitis c virus replication complexes with microtubules and actin filaments is dependent on the interaction of ns3 and ns5a. | the hepatitis c virus (hcv) rna replication complex (rc), which is composed of viral nonstructural (ns) proteins and host cellular proteins, replicates the viral rna genome in association with intracellular membranes. two viral ns proteins, ns3 and ns5a, are essential elements of the rc. here, by using immunoprecipitation and fluorescence resonance energy transfer assays, we demonstrated that ns3 and ns5a interact with tubulin and actin. furthermore, immunofluorescence microscopy and electron mi ... | 2008 | 18562541 |
| closing the door on flaviviruses: entry as a target for antiviral drug design. | with the emergence and rapid spread of west nile virus in the united states since 1999, and the 50-100 million infections per year caused by dengue virus globally, the threat of flaviviruses as re-emerging human pathogens has become a reality. to support the efforts that are currently being pursued to develop effective vaccines against these viruses, researchers are also actively pursuing the development of small molecule compounds that target various aspects of the virus life cycle. recent adva ... | 2008 | 18585795 |
| architects of assembly: roles of flaviviridae non-structural proteins in virion morphogenesis. | viruses of the flaviviridae family, including hepatitis c, dengue and bovine viral diarrhoea, are responsible for considerable morbidity and mortality worldwide. recent advances in our understanding of virion assembly have uncovered commonalities among distantly related members of this family. we discuss the emerging hypothesis that physical virion components are not alone in forming the infectious particle, but that non-structural proteins are intimately involved in orchestrating morphogenesis. ... | 2008 | 18587411 |
| genetic variation of st. louis encephalitis virus. | st. louis encephalitis virus (slev) has been regularly isolated throughout the americas since 1933. previous phylogenetic studies involving 62 isolates have defined seven major lineages (i-vii), further divided into 14 clades. in this study, 28 strains isolated in texas in 1991 and 2001-2003, and three older, previously unsequenced strains from jamaica and california were sequenced over the envelope protein gene. the inclusion of these new sequences, and others published since 2001, has allowed ... | 2008 | 18632961 |
| a complex rna motif defined by three discontinuous 5-nucleotide-long strands is essential for flavivirus rna replication. | tertiary or higher-order rna motifs that regulate replication of positive-strand rna viruses are as yet poorly understood. using japanese encephalitis virus (jev), we now show that a key element in jev rna replication is a complex rna motif that includes a string of three discontinuous complementary sequences (tdcs). the tdcs consists of three 5-nt-long strands, the left (l) strand upstream of the translation initiator aug adjacent to the 5'-end of the genome, and the middle (m) and right (r) st ... | 2008 | 18669441 |
| genetic and serologic properties of zika virus associated with an epidemic, yap state, micronesia, 2007. | zika virus (zikv) is a mosquito-borne flavivirus first isolated in uganda from a sentinel monkey in 1947. mosquito and sentinel animal surveillance studies have demonstrated that zikv is endemic to africa and southeast asia, yet reported human cases are rare, with <10 cases reported in the literature. in june 2007, an epidemic of fever and rash associated with zikv was detected in yap state, federated states of micronesia. we report the genetic and serologic properties of the zikv associated wit ... | 2008 | 18680646 |
| detection and serotyping of dengue virus in serum samples by multiplex reverse transcriptase pcr-ligase detection reaction assay. | the detection and successful typing of dengue virus (denv) from patients with suspected dengue fever is important both for the diagnosis of the disease and for the implementation of epidemiologic control measures. a technique for the multiplex detection and typing of denv serotypes 1 to 4 (denv-1 to denv-4) from clinical samples by pcr-ligase detection reaction (ldr) has been developed. a serotype-specific pcr amplifies the regions of genes c and e simultaneously. the two amplicons are targeted ... | 2008 | 18685000 |
| phosphorylation of yellow fever virus ns5 alters methyltransferase activity. | serine/threonine phosphorylation of the nonstructural protein 5 (ns5) is conserved feature of flaviviruses, but the kinase(s) responsible and function(s) remain unknown. mass spectrometry was used to characterize phosphorylated residues of yellow fever virus (yfv) ns5 expressed in mammalian cells. multiple different phosphopeptides were detected. mutational and additional mass spectrometry data implicated serine 56 (s56), a conserved residue near the active site in the ns5 methyltransferase doma ... | 2008 | 18757072 |
| molecular targets for flavivirus drug discovery. | flaviviruses are a major cause of infectious disease in humans. dengue virus causes an estimated 50 million cases of febrile illness each year, including an increasing number of cases of hemorrhagic fever. west nile virus, which recently spread from the mediterranean basin to the western hemisphere, now causes thousands of sporadic cases of encephalitis annually. despite the existence of licensed vaccines, yellow fever, japanese encephalitis and tick-borne encephalitis also claim many thousands ... | 2009 | 18796313 |
| analysis of flavivirus ns5 methyltransferase cap binding. | the flavivirus 2'-o-nucleoside n-terminal rna methyltransferase (mtase) enzyme is responsible for methylating the viral rna cap structure. to increase our understanding of the mechanism of viral rna cap binding we performed a detailed structural and biochemical characterization of the guanosine cap-binding pocket of the dengue (den) and yellow fever (yf) virus mtase enzymes. we solved an improved 2.1 a resolution crystal structure of den2 mtase, new 1.5 a resolution crystal structures of the yf ... | 2009 | 19101564 |
| ticks associated with macquarie island penguins carry arboviruses from four genera. | macquarie island, a small subantarctic island, is home to rockhopper, royal and king penguins, which are often infested with the globally distributed seabird tick, ixodes uriae. a flavivirus, an orbivirus, a phlebovirus, and a nairovirus were isolated from these ticks and partial sequences obtained. the flavivirus was nearly identical to gadgets gully virus, isolated some 30 year previously, illustrating the remarkable genetic stability of this virus. the nearest relative to the orbivirus (for w ... | 2009 | 19194498 |
| west nile virus envelope protein glycosylation is required for efficient viral transmission by culex vectors. | many, but not all, strains of west nile virus (wnv) contain a single n-linked glycosylation site on their envelope (e) proteins. previous studies have shown that e-glycosylated strains are more neuroinvasive in mice than non-glycosylated strains. e protein glycosylation also appears to play a role in attachment and entry of wnv into host cells in vitro; however, studies examining how e protein glycosylation affects the interactions of wnv with its mosquito vectors in vivo have not yet been perfo ... | 2009 | 19249803 |
| virus-specific cytolytic antibodies to nonstructural protein 1 of japanese encephalitis virus effect reduction of virus output from infected cells. | we demonstrate the presence of nonstructural protein 1 (ns1)-specific antibodies in a significant proportion of convalescent-phase human serum samples obtained from a cohort in an area where japanese encephalitis virus (jev) is endemic. sera containing antibodies to ns1 but not those with antibodies to other jev proteins, such as envelope, brought about complement-mediated lysis of jev-infected bhk-21 cells. target cells infected with a recombinant poxvirus expressing jev ns1 on the cell surface ... | 2009 | 19264772 |
| ns5 of dengue virus mediates stat2 binding and degradation. | the mammalian interferon (ifn) signaling pathway is a primary component of the innate antiviral response. as such, viral pathogens have devised multiple mechanisms to antagonize this pathway and thus facilitate infection. dengue virus (denv) encodes several proteins (ns2a, ns4a, and ns4b) that have been shown individually to inhibit the ifn response. in addition, denv infection results in reduced levels of expression of stat2, which is required for ifn signaling (m. jones, a. davidson, l. hibber ... | 2009 | 19279106 |
| helices alpha2 and alpha3 of west nile virus capsid protein are dispensable for assembly of infectious virions. | the internal hydrophobic sequence within the flaviviral capsid protein (protein c) plays an important role in the assembly of infectious virions. here, this sequence was analyzed in a west nile virus lineage i isolate (crow v76/1). an infectious cdna clone was constructed and used to introduce deletions into the internal hydrophobic domain which comprises helix alpha2 and part of the loop intervening helices alpha2 and alpha3. in total, nine capsid deletion mutants (4 to 14 amino acids long) wer ... | 2009 | 19297470 |
| isolation of genotype v st. louis encephalitis virus in florida. | we isolated and characterized st. louis encephalitis virus (slev) from cloacal swabs of naturally exposed adult sentinel chickens in 2006. phylogenetic analysis of slev strains isolated in florida indicated that brazilian slev circulated in 1972 and 2006; lineages were va and vb. | 2009 | 19331744 |
| glyceraldehyde-3-phosphate dehydrogenase (gapdh) interaction with 3' ends of japanese encephalitis virus rna and colocalization with the viral ns5 protein. | replication of the japanese encephalitis virus (jev) genome depends on host factors for successfully completing their life cycles; to do this, host factors have been recruited and/or relocated to the site of viral replication. glyceraldehyde-3-phosphate dehydrogenase (gapdh), a cellular metabolic protein, was found to colocalize with viral rna-dependent rna polymerase (ns5) in jev-infected cells. subcellular fractionation further indicated that gapdh remained relatively constant in the cytosol, ... | 2009 | 19368702 |
| measure and countermeasure: type i ifn (ifn-alpha/beta) antiviral response against west nile virus. | as a first line of defense after viral infection, host cells develop an intrinsic immune response to control virus dissemination and protect against serious infection. recent experiments have shown a dominant role of the ifn-alpha/beta response in protection against lethal west nile virus (wnv) by limiting the cellular and tissue tropism of infection. this review will focus on advances in identifying the host sensors that detect wnv and the adaptor molecules and signaling pathways that regulate ... | 2009 | 20375601 |
| emergent infectious uveitis. | infectious causes should always be considered in all patients with uveitis and it should be ruled out first. the differential diagnosis includes multiple well-known diseases including herpes, syphilis, toxoplasmosis, tuberculosis, bartonellosis, lyme disease, and others. however, clinicians should be aware of emerging infectious agents as potential causes of systemic illness and also intraocular inflammation. air travel, immigration, and globalization of business have overturned traditional patt ... | 2009 | 20404989 |
| changing patterns of west nile virus transmission: altered vector competence and host susceptibility. | west nile virus (wnv) is a flavivirus (flaviviridae) transmitted between culex spp. mosquitoes and avian hosts. the virus has dramatically expanded its geographic range in the past ten years. increases in global commerce, climate change, ecological factors and the emergence of novel viral genotypes likely play significant roles in the emergence of this virus; however, the exact mechanism and relative importance of each is uncertain. previously wnv was primarily associated with febrile illness of ... | 2009 | 19406093 |
| trans-complementation of an ns2 defect in a late step in hepatitis c virus (hcv) particle assembly and maturation. | recent studies using cell culture infection systems that recapitulate the entire life cycle of hepatitis c virus (hcv) indicate that several nonstructural viral proteins, including ns2, ns3, and ns5a, are involved in the process of viral assembly and release. other recent work suggests that ser-168 of ns2 is a target of ck2 kinase-mediated phosphorylation, and that this controls the stability of the genotype 1a ns2 protein. here, we show that ser-168 is a critical determinant in the production o ... | 2009 | 19412343 |
| the zoonotic flaviviruses of southern, south-eastern and eastern asia, and australasia: the potential for emergent viruses. | the genus flaviviridae comprises about 70 members, of which about 30 are found in southern, south-eastern and eastern asia and australasia. these include major pathogens such as japanese encephalitis (je), west nile (wn), murray valley encephalitis (mve), tick-borne encephalitis, kyasanur forest disease virus, and the dengue viruses. other members are known to be associated with mild febrile disease in humans, or with no known disease. in addition, novel flaviviruses continue to be discovered, a ... | 2009 | 19486319 |
| 3' cis-acting elements that contribute to the competence and efficiency of japanese encephalitis virus genome replication: functional importance of sequence duplications, deletions, and substitutions. | the positive-strand rna genome of japanese encephalitis virus (jev) terminates in a highly conserved 3'-noncoding region (3'ncr) of six domains (v, x, i, ii-1, ii-2, and iii in the 5'-to-3' direction). by manipulating the jev genomic rna, we have identified important roles for rna elements present within the 574-nucleotide 3'ncr in viral replication. the two 3'-proximal domains (ii-2 and iii) were sufficient for rna replication and virus production, whereas the remaining four (v, x, i, and ii-1) ... | 2009 | 19494005 |
| progress on the development of therapeutics against west nile virus. | a decade has passed since the appearance of west nile virus (wnv) in humans in the western hemisphere in new york city. during this interval, wnv spread inexorably throughout north and south america and caused millions of infections ranging from a sub-clinical illness, to a self-limiting febrile syndrome or lethal neuroinvasive disease. its entry into the united states triggered intensive research into the basic biology of wnv and the elements that comprise a protective host immune response. alt ... | 2009 | 19501622 |
| hepatitis c virus ns2 protein contributes to virus particle assembly via opposing epistatic interactions with the e1-e2 glycoprotein and ns3-ns4a enzyme complexes. | the hepatitis c virus ns2 protein has been recently implicated in virus particle assembly. to further understand the role of ns2 in this process, we conducted a reverse genetic analysis of ns2 in the context of a chimeric genotype 2a infectious cell culture system. of 32 mutants tested, all were capable of rna replication and 25 had moderate-to-severe defects in virus assembly. through forward genetic selection for variants capable of virus spread, we identified second-site mutations in e1, e2, ... | 2009 | 19515772 |
| 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 |
| development of resistance to passive therapy with a potently neutralizing humanized monoclonal antibody against west nile virus. | previous studies have established the therapeutic efficacy of humanized e16 (he16) monoclonal antibody against west nile virus in animals. here, we assess the potential for west nile virus strains encoding mutations in the he16 epitope to resist passive immunotherapy and for the selection of neutralization escape variants during he16 treatment. resistance to he16 in vivo was less common than expected, because several mutations that affected neutralization in vitro did not significantly affect pr ... | 2009 | 19527169 |
| theoretical study of the usutu virus helicase 3d structure, by means of computer-aided homology modelling. | background: usutu virus belongs to the flaviviridae viral family and constitutes an important pathogen. the viral helicase is an ideal target for inhibitor design, since this enzyme is essential for the survival, proliferation and transmission of the virus. results: towards a drug-design approach, the 3d model of the usutu virus helicase structure has been designed, using conventional homology modelling techniques and the known 3d-structure of the murray valley encephalitis virus helicase, of th ... | 2009 | 19555498 |
| west nile virus infection alters midgut gene expression in culex pipiens quinquefasciatus say (diptera: culicidae). | alterations in gene expression in the midgut of female culex pipiens quinquefasciatus exposed to blood meals containing 6.8 logs plaque-forming units/ml of west nile virus (wnv) were studied by fluorescent differential display. twenty-six different cdnas exhibited reproducible differences after feeding on infected blood. of these, 21 cdnas showed an increase in expression, and 5 showed a decrease in expression as a result of wnv presence in the blood meal. genbank database searches showed that o ... | 2009 | 19635880 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| long double-stranded rna induces an antiviral response independent of ifn regulatory factor 3, ifn-beta promoter stimulator 1, and ifn. | virus infection elicits a robust innate antiviral response dominated by the production of type 1 ifn. in nonprofessional innate immune cells such as fibroblasts, type 1 ifn is rapidly produced following the recognition of viral dsrna and the subsequent activation of the constitutively expressed transcription factor ifn regulatory factor 3 (irf3). although origin, localization, and length are factors in mediating dsrna recognition and binding by cellular dsrna-binding proteins, the biological sig ... | 2009 | 19864603 |
| arboviral diseases and malaria in australia, 2007/08: annual report of the national arbovirus and malaria advisory committee. | the national notifiable diseases surveillance system (nndss) received 8,671 notifications of diseases transmitted by mosquitoes in australia for the season 1 july 2007 to 30 june 2008. this represented a 39% increase from the annual average of 6,259 notifications for the previous 5 years. the alphaviruses, barmah forest and ross river, accounted for 7,760 (89%) of these notifications during the 2007/08 season and represents an increase when compared with the mean of the past 5 seasons. detection ... | 2009 | 19877534 |
| bovine viral diarrhea virus ns4b protein is an integral membrane protein associated with golgi markers and rearranged host membranes. | very little is known about bvdv ns4b, a protein of approximately 38 kda. however, a missense mutation in ns4b has been implicated in changing bvdv from a cytopathic to noncytopathic virus, suggesting that ns4b might play a role in bvdv pathogenesis. though this is one possible function, it is also likely that ns4b plays a role in bvdv genome replication. for example, bvdv ns4b interacts with ns3 and ns5a, implying that ns4b is part of a complex, which contains bvdv replicase proteins. other poss ... | 2009 | 19887001 |
| focus on flaviviruses: current and future drug targets. | infection by mosquito-borne flaviviruses (family flaviviridae) is increasing in prevalence worldwide. the vast global, social and economic impact due to the morbidity and mortality associated with the diseases caused by these viruses necessitates therapeutic intervention. there is currently no effective clinical treatment for any flaviviral infection. therefore, there is a great need for the identification of novel inhibitors to target the virus life cycle. | 2009 | 20165556 |
| activation of the antiviral kinase pkr and viral countermeasures. | the interferon-induced double-stranded (ds)rna-dependent protein kinase (pkr) limits viral replication by an eif2a-mediated block of translation. although many negative-strand rna viruses activate pkr, the responsible rnas have long remained elusive, as dsrna, the canonical activator of pkr, has not been detected in cells infected with such viruses. in this review we focus on the activating rna molecules of different virus families, in particular the negative-strand rna viruses. we discuss the r ... | 2009 | 21994559 |
| lipid metabolism and hcv infection. | chronic infection by hepatitis c virus (hcv) can lead to severe liver disease and is a global healthcare problem. the liver is highly metabolically active and one of its key functions is to control the balance of lipid throughout the body. a number of pathologies have been linked to the impact of hcv infection on liver metabolism. however, there is also growing evidence that hepatic metabolic processes contribute to the hcv life cycle. this review summarizes the relationship between lipid metabo ... | 2010 | 21994676 |
| rna replicons - a new approach for influenza virus immunoprophylaxis. | rna replicons are derived from either positive- or negative-strand rna viruses. they represent disabled virus vectors that are not only avirulent, but also unable to revert to virulence. due to autonomous rna replication, rna replicons are able to drive high level, cytosolic expression of recombinant antigens stimulating both the humoral and the cellular branch of the immune system. this review provides an update on the available literature covering influenza virus vaccines based on rna replicon ... | 2010 | 21994644 |
| 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 ... | 2010 | 21994652 |
| viral pathogenesis in mice is similar for west nile virus derived from mosquito and mammalian cells. | west nile virus (wnv) is a mosquito-borne pathogen. during replication, wnv acquires different carbohydrates and lipid membranes, depending on its mosquito or vertebrate hosts. consequently, wnv derived from mosquito and vertebrate cell lines differ in their infectivity for dendritic cells (dcs) and induction of type i interferon (ifn-alpha/beta) in vitro. we evaluated the pathogenesis of wnv derived from mosquito (wnv(c6/36)) and vertebrate (wnv(bhk)) cell lines in mice. the tissue tropism, inf ... | 2010 | 20167345 |
| immunotherapy for cervical cancer: research status and clinical potential. | the high-risk types of human papillomavirus (hpv) have been found to be associated with most cervical cancers and play an essential role in the pathogenesis of the disease. despite recent advances in preventive hpv vaccine development, such preventive vaccines are unlikely to reduce the prevalence of hpv infections within the next few years, due to their cost and limited availability in developing countries. furthermore, preventive hpv vaccines may not be capable of treating established hpv infe ... | 2010 | 20199126 |
| both e protein glycans adversely affect dengue virus infectivity but are beneficial for virion release. | the e protein of most flaviviruses is modified by asn-linked glycosylation at residue 153/154 and in the case of the four dengue virus (denv) serotypes by a second glycan at residue 67. however, the absence of e protein glycosylation among numerous natural isolates of different flaviviruses suggests that the glycan, per se, is not critically important in the virus life cycle. consistent with this notion, we show that ablation of both glycans from the denv-2 e protein reduces but does not prevent ... | 2010 | 20219924 |
| flavitrack analysis of the structure and function of west nile non-structural proteins. | the flavitrack database groups flaviviruses (fv), evolutionarily related organisms with high subtype variability, according to their phenotypes. here, pcpmer tools were used to calculate consensus sequences based on conservation of physicochemical properties (pcp) for 919 sequences of ns2a, a non-structural protein involved in preventing host interferon response to infection. conserved pcp-motifs were detected, primarily in the n-terminal half of ns2a. one model structure, based on a nuclear rec ... | 2010 | 20223736 |
| interplay of rna elements in the dengue virus 5' and 3' ends required for viral rna replication. | dengue virus (denv) is a member of the flavivirus genus of positive-sense rna viruses. denv rna replication requires cyclization of the viral genome mediated by two pairs of complementary sequences in the 5' and 3' ends, designated 5' and 3' cyclization sequences (5'-3' cs) and the 5' and 3' upstream of aug region (5'-3' uar). here, we demonstrate that another stretch of six nucleotides in the 5' end is involved in denv replication and possibly genome cyclization. this new sequence is located do ... | 2010 | 20357095 |
| identification of gbf1 as a cellular factor required for hepatitis c virus rna replication. | in infected cells, hepatitis c virus (hcv) induces the formation of membrane alterations referred to as membranous webs, which are sites of rna replication. in addition, hcv rna replication also occurs in smaller membrane structures that are associated with the endoplasmic reticulum. however, cellular mechanisms involved in the formation of hcv replication complexes remain largely unknown. here, we used brefeldin a (bfa) to investigate cellular mechanisms involved in hcv infection. bfa acts on c ... | 2010 | 19906930 |
| structure and functionality in flavivirus ns-proteins: perspectives for drug design. | flaviviridae are small enveloped viruses hosting a positive-sense single-stranded rna genome. besides yellow fever virus, a landmark case in the history of virology, members of the flavivirus genus, such as west nile virus and dengue virus, are increasingly gaining attention due to their re-emergence and incidence in different areas of the world. additional environmental and demographic considerations suggest that novel or known flaviviruses will continue to emerge in the future. nevertheless, u ... | 2010 | 19945487 |
| establishment of one-step sybr green-based real time-pcr assay for rapid detection and quantification of chikungunya virus infection. | chikungunya virus (chikv) is a mosquito-borne alphavirus and one of the prevalent re-emerging arbovirus in tropical and subtropical regions of asia, africa, and central and south america. it produces a spectrum of illness ranging from inapparent infection to moderate febrile illness as well as severe arthralgia or arthritis affecting multiple joints. in this study, a quantitative, one-step real-time sybr green-based rt-pcr system for the non-structural protein 2 (nsp2) of chikv that can quantify ... | 2010 | 20092632 |
| evidence for ribosomal frameshifting and a novel overlapping gene in the genomes of insect-specific flaviviruses. | flaviviruses have a positive-sense, single-stranded rna genome of approximately 11 kb, encoding a large polyprotein that is cleaved to produce approximately 10 mature proteins. cell fusing agent virus, kamiti river virus, culex flavivirus and several recently discovered flaviviruses have no known vertebrate host and apparently infect only insects. we present compelling bioinformatic evidence for a 253-295 codon overlapping gene (designated fifo) conserved throughout these insect-specific flavivi ... | 2010 | 20097399 |
| the ns5 protein of the virulent west nile virus ny99 strain is a potent antagonist of type i interferon-mediated jak-stat signaling. | flaviviruses transmitted by arthropods represent a tremendous disease burden for humans, causing millions of infections annually. all vector-borne flaviviruses studied to date suppress host innate responses to infection by inhibiting alpha/beta interferon (ifn-alpha/beta)-mediated jak-stat signal transduction. the viral nonstructural protein ns5 of some flaviviruses functions as the major ifn antagonist, associated with inhibition of ifn-dependent stat1 phosphorylation (py-stat1) or with stat2 d ... | 2010 | 20106931 |
| perspectives for preventive and therapeutic hpv vaccines. | human papillomavirus (hpv) has been associated with several human cancers, including cervical cancer, vulvar cancer, vaginal and anal cancer, and a subset of head and neck cancers. thus effective vaccination against hpv provides an opportunity to reduce the morbidity and mortality associated with hpv. the food and drug administration of the united states has approved two preventive vaccines to limit the spread of hpv. however, these are unlikely to impact upon hpv prevalence and cervical cancer ... | 2010 | 20123582 |
| mkrn1 induces degradation of west nile virus capsid protein by functioning as an e3 ligase. | west nile virus capsid protein (wnvcp) displays pathogenic toxicity via the apoptotic pathway. however, a cellular mechanism protective against this toxic effect has not been observed so far. here, we identified makorin ring finger protein 1 (mkrn1) as a novel e3 ubiquitin ligase for wnvcp. the cytotoxic effects of wnvcp as well as its expression levels were inhibited in u2os cells that stably expressed mkrn1. immunoprecipitation analyses revealed an interaction between mkrn1 and wnvcp. domain a ... | 2010 | 19846531 |
| present and future arboviral threats. | arthropod-borne viruses (arboviruses) are important causes of human disease nearly worldwide. all arboviruses circulate among wild animals, and many cause disease after spillover transmission to humans and agriculturally important domestic animals that are incidental or dead-end hosts. viruses such as dengue (denv) and chikungunya (chikv) that have lost the requirement for enzootic amplification now produce extensive epidemics in tropical urban centers. many arboviruses recently have increased i ... | 2010 | 19857523 |
| should there be a standardised approach to the diagnostic workup of suspected adult encephalitis? a case series from australia. | the clinical diagnosis of encephalitis is often difficult and identification of a causative organism is infrequent. the encephalitis syndrome may herald the emergence of novel pathogens with outbreak potential. individual treatment and an effective public health response rely on identifying a specific pathogen. in australia there have been no studies to try to improve the identification rate of encephalitis pathogens. this study aims to review the diagnostic assessment of adult suspected encepha ... | 2010 | 21159185 |
| viral reorganization of the secretory pathway generates distinct organelles for rna replication. | many rna viruses remodel intracellular membranes to generate specialized sites for rna replication. how membranes are remodeled and what properties make them conducive for replication are unknown. here we show how rna viruses can manipulate multiple components of the cellular secretory pathway to generate organelles specialized for replication that are distinct in protein and lipid composition from the host cell. specific viral proteins modulate effector recruitment by arf1 gtpase and its guanin ... | 2010 | 20510927 |
| west nile virus. | west nile virus (wnv) is responsible for thousands of cases of morbidity and mortality in birds, horses, and humans. epidemics were localized to europe, africa, the middle east, and parts of asia, and primarily caused a mild febrile illness in humans. in the late 1990s, the virus became more virulent and spread to north america. in humans, the clinical presentation ranges from asymptomatic, seen frequently, to encephalitis/paralysis and death, seen rarely. there is no fda (food and drug administ ... | 2010 | 20513541 |
| experimental studies of the role of the little raven (corvus mellori) in surveillance for west nile virus in australia. | to study the potential role of an australian corvid, the little raven (corvus mellori), in the surveillance for exotic west nile virus (wnv) in australia. | 2010 | 20553567 |
| tick-borne encephalitis virus delays interferon induction and hides its double-stranded rna in intracellular membrane vesicles. | tick-borne encephalitis virus (tbev) (family flaviviridae, genus flavivirus) accounts for approximately 10,000 annual cases of severe encephalitis in europe and asia. here, we investigated the induction of the antiviral type i interferons (ifns) (alpha/beta ifn [ifn-alpha/beta]) by tbev. using strains neudörfl, hypr, and absettarov, we demonstrate that levels of ifn-beta transcripts and viral rna are strictly correlated. moreover, ifn induction by tbev was dependent on the transcription factor i ... | 2010 | 20554782 |
| meta-analysis of all immune epitope data in the flavivirus genus: inventory of current immune epitope data status in the context of virus immunity and immunopathology. | a meta-analysis was performed in order to inventory the immune epitope data related to viruses in the genus flavivirus. nearly 2000 epitopes were captured from over 130 individual flavivirus-related references identified from pubmed and reported as of september 2009. this report includes all epitope structures and associated immune reactivity from the past and current literature, including: the epitope distribution among pathogens and related strains, the epitope distribution among different pat ... | 2010 | 20565291 |
| false-positive transcription-mediated amplification assay detection of west nile virus in blood from a patient with viremia caused by an usutu virus infection. | detection of west nile virus (wnv) by nucleic acid amplification technology (naat) is used widely to screen blood and organ donations in areas where wnv is endemic. we report a false-positive result of a wnv transcription-mediated amplification assay (tma) in a patient with viremia that was caused by usutu virus, a mosquito-borne flavivirus. | 2010 | 20592138 |
| characterization of dengue virus resistance to brequinar in cell culture. | brequinar is an inhibitor of dihydroorotate dehydrogenase, an enzyme that is required for de novo pyrimidine biosynthesis. here we report that brequinar has activity against a broad spectrum of viruses. the compound not only inhibits flaviviruses (dengue virus, west nile virus, yellow fever virus, and powassan virus) but also suppresses a plus-strand rna alphavirus (western equine encephalitis virus) and a negative-strand rna rhabdovirus (vesicular stomatitis virus). using dengue virus serotype ... | 2010 | 20606073 |
| construction of a dengue virus type 4 reporter replicon and analysis of temperature-sensitive mutations in non-structural proteins 3 and 5. | replicon systems have been useful to study mechanisms of translation and replication of flavivirus rnas. in this study, we constructed a dengue virus 4 replicon encoding a renilla luciferase (r(luc)) reporter, and six single-residue substitution mutants were generated: l128f and s158p in the non-structural protein (ns) 3 protease domain gene, and n96i, n390a, k437r and m805i in the ns5 gene. the effects of these substitutions on viral rna translation and/or replication were examined by measuring ... | 2010 | 20631089 |
| arboviral encephalitides: transmission, emergence, and pathogenesis. | arthropod-borne viruses (arboviruses) are of paramount concern as a group of pathogens at the forefront of emerging and re-emerging diseases. although some arboviral infections are asymptomatic or present with a mild influenza-like illness, many are important human and veterinary pathogens causing serious illness ranging from rash and arthritis to encephalitis and hemorrhagic fever. here, we discuss arboviruses from diverse families (flaviviruses, alphaviruses, and the bunyaviridae) that are cau ... | 2010 | 20652430 |
| structural and functional analyses of a conserved hydrophobic pocket of flavivirus methyltransferase. | the flavivirus methyltransferase (mtase) sequentially methylates the n7 and 2'-o positions of the viral rna cap (gpppa-rna → m(7)gpppa-rna → m(7)gpppam-rna), using s-adenosyl-l-methionine (adomet) as a methyl donor. we report here that sinefungin (sin), an adomet analog, inhibits several flaviviruses through suppression of viral mtase. the crystal structure of west nile virus mtase in complex with sin inhibitor at 2.0-å resolution revealed a flavivirus-conserved hydrophobic pocket located next t ... | 2010 | 20685660 |
| the endoplasmic reticulum provides the membrane platform for biogenesis of the flavivirus replication complex. | the cytoplasmic replication of positive-sense rna viruses is associated with a dramatic rearrangement of host cellular membranes. these virus-induced changes result in the induction of vesicular structures that envelop the virus replication complex (rc). in this study, we have extended our previous observations on the intracellular location of west nile virus strain kunjin virus (wnv(kun)) to show that the virus-induced recruitment of host proteins and membrane appears to occur at a pre-golgi st ... | 2010 | 20686019 |