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genetic characterization of yokose virus, a flavivirus isolated from the bat in japan.yokose virus (strain oita-36) was isolated from the bat in japan in 1971. in the present study, we determined complete nucleotide sequences of yokose virus using rt-pcr and race techniques. yokose virus genome consists of 10,857 nucleotides in length (accession no. ab114858), containing a single open reading frame (3425 amino acids) encoding 11 viral proteins. we deduced the boundaries of each protein in the polyprotein sequence according to the protein cleavage sites of other flaviviruses. the ...200515661139
the modeled structure of the rna dependent rna polymerase of gbv-c virus suggests a role for motif e in flaviviridae rna polymerases.the flaviviridae virus family includes major human and animal pathogens. the rna dependent rna polymerase (rdrp) plays a central role in the replication process, and thus is a validated target for antiviral drugs. despite the increasing structural and enzymatic characterization of viral rdrps, detailed molecular replication mechanisms remain unclear. the hepatitis c virus (hcv) is a major human pathogen difficult to study in cultured cells. the bovine viral diarrhea virus (bvdv) is often used as ...200516225688
bats: important reservoir hosts of emerging viruses.bats (order chiroptera, suborders megachiroptera ["flying foxes"] and microchiroptera) are abundant, diverse, and geographically widespread. these mammals provide us with resources, but their importance is minimized and many of their populations and species are at risk, even threatened or endangered. some of their characteristics (food choices, colonial or solitary nature, population structure, ability to fly, seasonal migration and daily movement patterns, torpor and hibernation, life span, roo ...200616847084
preliminary characterization of (nucleoside-2'-o-)-methyltransferase crystals from meaban and yokose flaviviruses.viral methyltranferases (mtase) are involved in the third step of the mrna-capping process, transferring a methyl group from s-adenosyl-l-methionine (sam) to the capped mrna. mtases are classified into two groups: (guanine-n7)-methyltransferases (n7mtases), which add a methyl group onto the n7 atom of guanine, and (nucleoside-2'-o-)-methyltransferases (2'omtases), which add a methyl group to a ribose hydroxyl. the mtases of two flaviviruses, meaban and yokose viruses, have been overexpressed, pu ...200616880552
development of multiplex real-time reverse transcriptase pcr assays for detecting eight medically important flaviviruses in mosquitoes.a multiplex real-time reverse transcriptase pcr has been developed for the rapid detection and identification of eight medically important flaviviruses from laboratory-reared, virus-infected mosquito pools. the method used involves the gene-specific amplification of yellow fever virus (yfv), japanese encephalitis virus (jev), west nile virus (wnv), st. louis encephalitis virus (slev), and dengue virus (denv) serotypes 1 to 4 (denv-1 to denv-4, respectively) by use of the flavivirus consensus amp ...200717108075
detection of antibodies to japanese encephalitis virus in the wild boars in hiroshima prefecture, japan.serum specimens were collected from 25 wild boars in hiroshima prefecture located in the western region of japan from november 2004 to february 2005. the sera were tested for antibodies to japanese encephalitis virus (jev) by igm capture and igg enzyme-linked immunosorbent assays (elisa), and plaque reduction neutralization test. seventeen samples (68%) were positive for neutralizing antibody to jev. all the neutralizing antibody-positive samples were positive for igg-elisa. one was also positiv ...200717217550
curation of viral genomes: challenges, applications and the way forward.whole genome sequence data is a step towards generating the 'parts list' of life to understand the underlying principles of biocomplexity. genome sequencing initiatives of human and model organisms are targeted efforts towards understanding principles of evolution with an application envisaged to improve human health. these efforts culminated in the development of dedicated resources. whereas a large number of viral genomes have been sequenced by groups or individuals with an interest to study a ...200617254296
structural bases for substrate recognition and activity in meaban virus nucleoside-2'-o-methyltransferase.viral methyltransferases are involved in the mrna capping process, resulting in the transfer of a methyl group from s-adenosyl-l-methionine to capped rna. two groups of methyltransferases (mtases) are known: (guanine-n7)-methyltransferases (n7mtases), adding a methyl group onto the n7 atom of guanine, and (nucleoside-2'-o-)-methyltransferases (2'omtases), adding a methyl group to a ribose hydroxyl. we have expressed and purified two constructs of meaban virus (mv; genus flavivirus) ns5 protein m ...200717473012
ligation-mediated amplification for effective rapid determination of viral rna sequences (rdv).emerging infectious diseases pose a significant risk to public health. methods for rapid detection of pathogens are needed to effectively treat these diseases. recently, we developed new methods for the rapid determination of viral rna sequences, rdv ver1.0 and ver2.0. we demonstrated that these methods were able to simultaneously detect cdna fragments of many different viruses without using sequence specific primers. however, some species of viruses, including the yokose virus (yokv), a flavivi ...200818595773
epizootology and experimental infection of yokose virus in bats.to reveal whether bats serve as an amplifying host for yokose virus (yokv), we conducted a serological survey and experimentally infected fruit bats with yokv isolated from microbats in japan. yokv belongs to the entebbe bat virus group of vector unknown group within the genus flavivirus and family flaviviridae. to detect antibodies against yokv, we developed an enzyme-linked immunosorbent assay (elisa) using biotinylated anti-bat igg rabbit sera. serological surveillance was conducted with samp ...201018789527
crystal structure of a methyltransferase from a no-known-vector flavivirus.presently known flaviviruses belong to three major evolutionary branches: tick-borne viruses, mosquito-borne viruses and viruses with no known vector. here we present the crystal structure of the yokose virus methyltransferase at 1.7a resolution, the first structure of a methyltransferase of a flavivirus with no known vector. structural comparison of three methyltransferases representative of each of the flavivirus branches shows that fold and structures are closely conserved, most differences b ...200919275894
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 ...200919570865
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 ...200919617912
structure of yellow fever virus envelope protein domain iii.the structure of recombinant domain iii of the envelope protein (red3) of yellow fever virus (yfv), containing the major neutralization site, was determined using nmr spectroscopy. the amino acid sequence and structure of the yfv-red3 shows differences from ed3s of other mosquito-borne flaviviruses; in particular, the partially surface-exposed bc loop where methionine-304 and valine-324 were identified as being critical for the structure of the loop. variations in the structure and surface chemi ...200919818466
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 ...201019945487
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 ...201020685660
flavivirus rna cap methyltransferase: structure, function, and inhibition.many flaviviruses are significant human pathogens. the plus-strand rna genome of a flavivirus contains a 5' terminal cap 1 structure (m(7)gpppamg). the flavivirus encodes one methyltransferase (mtase), located at the n-terminal portion of the ns5 rna-dependent rna polymerase (rdrp). here we review recent advances in our understanding of flaviviral capping machinery and the implications for drug development. the ns5 mtase catalyzes both guanine n7 and ribose 2'-oh methylations during viral cap fo ...201021927615
Tembusu virus in ducks, china.In China in 2010, a disease outbreak in egg-laying ducks was associated with a flavivirus. The virus was isolated and partially sequenced. The isolate exhibited 87%-91% identity with strains of Tembusu virus, a mosquito-borne flavivirus of the Ntaya virus group. These findings demonstrate emergence of Tembusu virus in ducks.201122000358
Molecular evolution of the insect-specific flaviviruses.There has been an explosion in the discovery of 'insect-specific' flaviviruses and/or their related sequences in natural mosquito populations. Herein we review all 'insect-specific' flaviviral sequences currently available and conduct phylogenetic analyses of both the 'insect-specific' flaviviruses and available sequences of the entire genus Flavivirus. We show that there is no statistical support for virus-mosquito co-divergence, suggesting that the 'insect-specific' flaviviruses may have under ...201122012464
biological transmission of arboviruses: reexamination of and new insights into components, mechanisms, and unique traits as well as their evolutionary trends.among animal viruses, arboviruses are unique in that they depend on arthropod vectors for transmission. field research and laboratory investigations related to the three components of this unique mode of transmission, virus, vector, and vertebrate host, have produced an enormous amount of valuable information that may be found in numerous publications. however, despite many reviews on specific viruses, diseases, or interests, a systematic approach to organizing the available information on all f ...016223950
bed bugs and infectious disease: a case for the arboviruses. 201323966852
noncoding subgenomic flavivirus rna: multiple functions in west nile virus pathogenesis and modulation of host responses.flaviviruses are a large group of positive strand rna viruses transmitted by arthropods that include many human pathogens such as west nile virus (wnv), japanese encephalitis virus (jev), yellow fever virus, dengue virus, and tick-borne encephalitis virus. all members in this genus tested so far are shown to produce a unique subgenomic flavivirus rna (sfrna) derived from the 3' untranslated region (utr). sfrna is a product of incomplete degradation of genomic rna by the cell 5'-3' exoribonucleas ...201424473339
a glance at subgenomic flavivirus rnas and micrornas in flavivirus infections.the family flaviviridae comprises a wide variety of viruses that are distributed worldwide, some of which are associated with high rates of morbidity and mortality. there are neither vaccines nor antivirals for most flavivirus infections, reinforcing the importance of research on different aspects of the viral life cycle. during infection, cytoplasmic accumulation of rna fragments mainly originating from the 3' utrs, which have been designated subgenomic flavivirus rnas (sfrnas), has been detect ...201627233361
ecuador paraiso escondido virus, a new flavivirus isolated from new world sand flies in ecuador, is the first representative of a novel clade in the genus flavivirus.a new flavivirus, ecuador paraiso escondido virus (epev), named after the village where it was discovered, was isolated from sand flies (psathyromyia abonnenci, formerly lutzomyia abonnenci) that are unique to the new world. this represents the first sand fly-borne flavivirus identified in the new world. epev exhibited a typical flavivirus genome organization. nevertheless, the maximum pairwise amino acid sequence identity with currently recognized flaviviruses was 52.8%. phylogenetic analysis o ...201526355096
new insights into flavivirus evolution, taxonomy and biogeographic history, extended by analysis of canonical and alternative coding sequences.to generate the most diverse phylogenetic dataset for the flaviviruses to date, we determined the genomic sequences and phylogenetic relationships of 14 flaviviruses, of which 10 are primarily associated with culex spp. mosquitoes. we analyze these data, in conjunction with a comprehensive collection of flavivirus genomes, to characterize flavivirus evolutionary and biogeographic history in unprecedented detail and breadth. based on the presumed introduction of yellow fever virus into the americ ...201525719412
novel flaviviruses from mosquitoes: mosquito-specific evolutionary lineages within the phylogenetic group of mosquito-borne flaviviruses.novel flaviviruses that are genetically related to pathogenic mosquito-borne flaviviruses (mbfv) have been isolated from mosquitoes in various geographical locations, including finland. we isolated and characterized another novel virus of this group from finnish mosquitoes collected in 2007, designated as ilomantsi virus (ilov). unlike the mbfv that infect both vertebrates and mosquitoes, the mbfv-related viruses appear to be specific to mosquitoes similar to the insect-specific flaviviruses (is ...201425108382
usutu virus: an emerging flavivirus in europe.usutu virus (usuv) is an african mosquito-borne flavivirus belonging to the japanese encephalitis virus serocomplex. usuv is closely related to murray valley encephalitis virus, japanese encephalitis virus, and west nile virus. usuv was discovered in south africa in 1959. in europe, the first true demonstration of circulation of usuv was reported in austria in 2001 with a significant die-off of eurasian blackbirds. in the subsequent years, usuv expanded to neighboring countries, including italy, ...201525606971
characterization of a novel insect-specific flavivirus from brazil: potential for inhibition of infection of arthropod cells with medically important flaviviruses.in the past decade, there has been an upsurge in the number of newly described insect-specific flaviviruses isolated pan-globally. we recently described the isolation of a novel flavivirus (tentatively designated 'nhumirim virus'; nhuv) that represents an example of a unique subset of apparently insect-specific viruses that phylogenetically affiliate with dual-host mosquito-borne flaviviruses despite appearing to be limited to replication in mosquito cells. we characterized the in vitro growth p ...201425146007
rapid evolutionary dynamics of structural disorder as a potential driving force for biological divergence in flaviviruses.protein structure is commonly regarded to be conserved and to dictate function. most proteins rely on conformational flexibility to some degree. are regions that convey conformational flexibility conserved over evolutionary time? can changes in conformational flexibility alter protein function? here, the evolutionary dynamics of structurally ordered and disordered (flexible) regions are investigated genome-wide in flaviviruses, revealing that the amount and location of structural disorder fluctu ...023418179
flaviviruses in europe: complex circulation patterns and their consequences for the diagnosis and control of west nile disease.in europe, many flaviviruses are endemic (west nile, usutu, tick-borne encephalitis viruses) or occasionally imported (dengue, yellow fever viruses). due to the temporal and geographical co-circulation of flaviviruses in europe, flavivirus differentiation by diagnostic tests is crucial in the adaptation of surveillance and control efforts. serological diagnosis of flavivirus infections is complicated by the antigenic similarities among the flavivirus genus. indeed, most flavivirus antibodies are ...201324225644
viral rna switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization.viral replicase recruitment and long-range rna interactions are essential for rna virus replication, yet the mechanism of their interplay remains elusive. flaviviruses include numerous important human pathogens, e.g., dengue virus (denv) and zika virus (zikv). here, we revealed a highly conserved, conformation-tunable cis-acting element named 5'-uar-flanking stem (ufs) in the flavivirus genomic 5' terminus. we demonstrated that the ufs was critical for efficient ns5 recruitment and viral rna syn ...201627692070
flavidb: a data mining system for knowledge discovery in flaviviruses with direct applications in immunology and vaccinology.the flavivirus genus is unusually large, comprising more than 70 species, of which more than half are known human pathogens. it includes a set of clinically relevant infectious agents such as dengue, west nile, yellow fever, and japanese encephalitis viruses. although these pathogens have been studied extensively, safe and efficient vaccines lack for the majority of the flaviviruses.025544857
detection of entebbe bat virus after 54 years.entebbe bat virus (entv; flaviviridae: flavivirus), closely related to yellow fever virus, was first isolated from a little free-tailed bat (chaerephon pumilus) in uganda in 1957, but was not detected after that initial isolation. in 2011, we isolated entv from a little free-tailed bat captured from the attic of a house near where it had originally been found. infectious virus was recovered from the spleen and lung, and the viral rna was sequenced and compared with that of the original isolate. ...201526101270
a fatal yellow fever virus infection in china: description and lessons.yellow fever (yf) is a viral disease endemic to the tropical regions of africa and south america. an outbreak of yf has been occurring in angola, since the beginning of 2016. in march 2016, a 32-year-old chinese man who returned from angola was hospitalized and diagnosed with the first case of imported yf in china. clinical observations, blood viral rna detection, serological testing and treatments for the patient were performed daily. the virus was isolated in vero cells, and the complete viral ...201627406389
detection of quang binh virus from mosquitoes in china.flaviviruses present a wide range of genetic diversity and exhibit diverse host relationships. mosquito-borne flaviviruses have recently been isolated and characterized worldwide. yunnan province of china is one of the richest areas of species diversity and is the center of multi-species evolution in mainland asia, which supports the circulation of numerous arthropod-borne viruses (arboviruses). in a screening program of arboviruses, mosquitoes were collected during the mosquito activity season ...201424342141
a review of flaviviruses that have no known arthropod vector.most viruses in the genus flavivirus are horizontally transmitted between hematophagous arthropods and vertebrate hosts, but some are maintained in arthropod- or vertebrate-restricted transmission cycles. flaviviruses maintained by vertebrate-only transmission are commonly referred to as no known vector (nkv) flaviviruses. fourteen species and two subtypes of nkv flaviviruses are recognized by the international committee on taxonomy of viruses (ictv), and tamana bat virus potentially belongs to ...201728635667
genetic diversity of the yokose virus, xybx1332, isolated from bats (myotis daubentonii) in china.yokose virus was first isolated from bats (miniopterus fuliginosus) collected in yokosuka, japan, in 1971, and is a new member of the family flaviviridae, genus flavivirus. in this study, we isolated a yokose virus from a serum sample of myotis daubentonii (order chiroptera, family vespertilionidae) collected in yunnan province, china in 2013.201930634973
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