| illness caused by a kokobera-like virus in south-eastern australia. | three patients who lived in south-eastern australia and who suffered acute polyarticular illnesses in the summer months of 1983-1984 and 1984-1985 are described. two patients lived in the southwestern plains of new south wales and one in bairnsdale in eastern victoria. serological studies implicated kokobera virus, a flavivirus, as the likely causative agent. this would appear to be the first report to indicate the pathogenicity of kokobera virus. | 1986 | 3016489 |
| the molecular epidemiology of kokobera virus. | we describe herein the molecular epidemiology and phylogeny of kokobera (kok) virus, a flavivirus found in australia and papua new guinea. we sequenced a region encompassing the 200 nucleotides of the 3' terminus of the ns5 gene, and the first 300 nucleotides of the 3' untranslated region (utr). the study included 25 isolates of the virus, including an isolate from png, and several recent isolates from the south-west of western australia (wa), where the virus had not previously been detected. we ... | 2000 | 10930658 |
| flaviviruses isolated from mosquitoes collected during the first recorded outbreak of japanese encephalitis virus on cape york peninsula, australia. | in response to an outbreak of japanese encephalitis (je) virus on cape york peninsula, australia, in 1998, mosquitoes were collected using co2 and octenol-baited centers for disease control and prevention light traps. a total of 35,235 adult mosquitoes, comprising 31 species, were processed for virus isolation. no isolates of je virus were recovered from these mosquitoes. however, 18 isolates of kokobera virus, another flavivirus were obtained from culex annulirostris. twelve isolates were from ... | 2001 | 11442206 |
| sucrose density gradient centrifugation and cross-flow filtration methods for the production of arbovirus antigens inactivated by binary ethylenimine. | sucrose density gradient centrifugation and cross-flow filtration methods have been developed and standardised for the safe and reproducible production of inactivated arbovirus antigens which are appropriate for use in diagnostic serological applications. | 2004 | 14720306 |
| identification of new flaviviruses in the kokobera virus complex. | novel flavivirus isolates from mosquitoes collected in northern australia were analysed by partial genomic sequencing, monoclonal antibody-binding assays and polyclonal cross-neutralization tests. two isolates were found to be antigenically distinct from, but related to, viruses of the kokobera virus complex, which currently contains kokobera (kokv) and stratford (strv) viruses. nucleotide sequence comparison of two separate regions of the genome revealed that an isolate from saibai island in th ... | 2005 | 15604438 |
| development of immunoglobulin m capture enzyme-linked immunosorbent assay to differentiate human flavivirus infections occurring in australia. | we report the development of a flavivirus immunoglobulin m (igm) capture enzyme-linked immunosorbent assay (mac-elisa) which improves the determination of an infecting flavivirus serotype over that by current serological methods. a panel of 165 igm-positive sera from flavivirus patients with specific diagnostic results was tested by the flavivirus mac-elisa using a panel of 10 antigens. for 134 of these sera (81.2%), the highest reactivity was demonstrated against the infecting virus, which was ... | 2005 | 15753249 |
| 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 |
| 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 |
| 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 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 ... | 2009 | 19818466 |
| duck egg-drop syndrome caused by byd virus, a new tembusu-related flavivirus. | since april 2010, a severe outbreak of duck viral infection, with egg drop, feed uptake decline and ovary-oviduct disease, has spread around the major duck-producing regions in china. a new virus, named byd virus, was isolated in different areas, and a similar disease was reproduced in healthy egg-producing ducks, infecting with the isolated virus. the virus was re-isolated from the affected ducks and replicated well in primary duck embryo fibroblasts and vero cells, causing the cytopathic effec ... | 2011 | 21455312 |
| 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. | 2011 | 22000358 |
| enhanced arbovirus surveillance with deep sequencing: identification of novel rhabdoviruses and bunyaviruses in australian mosquitoes. | viral metagenomics characterizes known and identifies unknown viruses based on sequence similarities to any previously sequenced viral genomes. a metagenomics approach was used to identify virus sequences in australian mosquitoes causing cytopathic effects in inoculated mammalian cell cultures. sequence comparisons revealed strains of liao ning virus (reovirus, seadornavirus), previously detected only in china, livestock-infecting stretch lagoon virus (reovirus, orbivirus), two novel dimarhabdov ... | 2013 | 24314645 |
| 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 ... | 0 | 16223950 |
| 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 ... | 2015 | 26355096 |
| 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 ... | 2015 | 25719412 |
| 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 ... | 2014 | 25146007 |
| dengue virus rna structure specialization facilitates host adaptation. | many viral pathogens cycle between humans and insects. these viruses must have evolved strategies for rapid adaptation to different host environments. however, the mechanistic basis for the adaptation process remains poorly understood. to study the mosquito-human adaptation cycle, we examined changes in rna structures of the dengue virus genome during host adaptation. deep sequencing and rna structure analysis, together with fitness evaluation, revealed a process of host specialization of rna el ... | 2015 | 25635835 |
| west nile virus (kunjin subtype) disease in the northern territory of australia--a case of encephalitis and review of all reported cases. | west nile virus kunjin subtype (wnv/kunv) is enzootic across the tropical north of australia, with epizootic spread into other jurisdictions. the clinical spectrum of illness in humans is poorly described. we report a clinical case of wnv/kunv encephalitis and performed a retrospective chart audit of all cases of wnv/kunv notified in the northern territory from 1992 to 2010. thirteen cases of wnv/kunv disease were identified; case notes were available for 10 of these presentations. six of these ... | 2011 | 22049056 |
| 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 |
| 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 |
| structure and biochemical analysis of kokobera virus helicase. | | 2008 | 18004778 |
| purification and crystallization of kokobera virus helicase. | kokobera virus is a mosquito-borne flavivirus belonging, like west nile virus, to the japanese encephalitis virus serocomplex. the flavivirus genus is characterized by a positive-sense single-stranded rna genome. the unique open reading frame of the viral rna is transcribed and translated as a single polyprotein which is post-translationally cleaved to yield three structural and seven nonstructural proteins, one of which is the ns3 gene that encodes a c-terminal helicase domain consisting of 431 ... | 2007 | 17329812 |
| flavivirus isolations from mosquitoes collected from western cape york peninsula, australia, 1999-2000. | after the 1st appearance of japanese encephalitis virus (je) on mainland australia in 1998, a study was undertaken to investigate whether je had become established in enzootic transmission cycles on western cape york peninsula. adult mosquitoes were collected during the late wet season from kowanyama and pormpuraaw in april 1999, and pormpuraaw and barr's yard in april 2000. despite processing 269,270 mosquitoes for virus isolation, no isolates of je were obtained. however, other flaviviruses co ... | 2003 | 14710742 |
| infection of western gray kangaroos (macropus fuliginosus) with australian arboviruses associated with human infection. | more than 75 arboviruses (arthropod-borne viruses) have been identified in australia. while alfuy virus (alfv), barmah forest virus (bfv), edge hill virus (ehv), kokobera virus (kokv), murray valley encephalitis virus (mvev), sindbis virus (sinv), ross river virus (rrv), stratford virus (strv), and west nile virus strain kunjin (kunv) have been associated with human infection, there remains a paucity of data regarding their respective transmission cycles and any potential nonhuman vertebrate hos ... | 2020 | 31556842 |
| molecular mechanism of divalent-metal-induced activation of ns3 helicase and insights into zika virus inhibitor design. | zika virus has attracted increasing attention because of its potential for causing human neural disorders, including microcephaly in infants and guillain-barré syndrome. its ns3 helicase domain plays critical roles in ntp-dependent rna unwinding and translocation during viral replication. our structural analysis revealed a pre-activation state of ns3 helicase in complex with gtpγs, in which the triphosphate adopts a compact conformation in the absence of any divalent metal ions. in contrast, in ... | 2016 | 27915293 |
| structure of the ns3 helicase from zika virus. | zika virus has emerged as a pathogen of major health concern. here, we present a high-resolution (1.62-å) crystal structure of the rna helicase from the french polynesia strain. the structure is similar to that of the rna helicase from dengue virus, with variability in the conformations of loops typically involved in binding atp and rna. we identify druggable 'hotspots' that are well suited for in silico and/or fragment-based high-throughput drug discovery. | 2016 | 27399257 |
| 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. | 0 | 25544857 |
| development of monoclonal antibodies to west nile virus and their application in immunohistochemistry. | west nile virus (wnv) is endemic throughout africa, eurasia, america, and australia and has important implications for avian, horse, and human health. in these regions, dead birds are monitored for the presence of wnv through immunohistochemistry (ihc) and pcr. however, a number of the tools for ihc are inadequate owing to their cross-reactivity to other japanese encephalitis serogroup viruses. here we have established eight monoclonal antibodies (mabs) to wnv. four of them bound to the envelope ... | 2012 | 22993408 |
| 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 ... | 0 | 23418179 |
| novel cis-acting element within the capsid-coding region enhances flavivirus viral-rna replication by regulating genome cyclization. | cis-acting elements in the viral genome rna (vrna) are essential for the translation, replication, and/or encapsidation of rna viruses. in this study, a novel conserved cis-acting element was identified in the capsid-coding region of mosquito-borne flavivirus. the downstream of 5' cyclization sequence (5'cs) pseudoknot (dcs-pk) element has a three-stem pseudoknot structure, as demonstrated by structure prediction and biochemical analysis. using dengue virus as a model, we show that dcs-pk enhanc ... | 2013 | 23576500 |
| viral rna intermediates as targets for detection and discovery of novel and emerging mosquito-borne viruses. | mosquito-borne viruses encompass a range of virus families, comprising a number of significant human pathogens (e.g., dengue viruses, west nile virus, chikungunya virus). virulent strains of these viruses are continually evolving and expanding their geographic range, thus rapid and sensitive screening assays are required to detect emerging viruses and monitor their prevalence and spread in mosquito populations. double-stranded rna (dsrna) is produced during the replication of many of these virus ... | 2015 | 25799391 |
| molecular phylogeny of edge hill virus supports its position in the yellow fever virus group and identifies a new genetic variant. | edge hill virus (ehv) is a mosquito-borne flavivirus isolated throughout australia during mosquito surveillance programs. while not posing an immediate threat to the human population, ehv is a taxonomically interesting flavivirus since it remains the only member of the yellow fever virus (yfv) sub-group to be detected within australia. here we present both an antigenic and genetic investigation of collected isolates, and confirm taxonomic classification of the virus within the yfv-group. isolate ... | 2010 | 20938485 |
| mechanism and specificity of a symmetrical benzimidazolephenylcarboxamide helicase inhibitor. | this study examines the effects of 1-n,4-n-bis[4-(1h-benzimidazol-2-yl)phenyl]benzene-1,4-dicarboxamide ((bip)(2)b) on the ns3 helicase encoded by the hepatitis c virus (hcv). molecular beacon-based helicase assays were used to show that (bip)(2)b inhibits the ability of hcv helicase to separate a variety of rna and dna duplexes with half-maximal inhibitory concentrations ranging from 0.7 to 5 microm, depending on the nature of the substrate. in single turnover assays, (bip)(2)b only inhibited u ... | 2010 | 20108979 |
| pcp consensus sequences of flaviviruses: correlating variance with vector competence and disease phenotype. | computational methods are needed to design multivalent vaccines against flaviviruses (fvs) such as the west nile virus or the dengue virus (denv). | 2010 | 19969003 |
| 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 |
| genetic divergence among members of the kokobera group of flaviviruses supports their separation into distinct species. | the kokobera virus group comprises mosquito-borne flaviviruses that cluster together phylogenetically. these viruses are unique to australia and papua new guinea, and have been associated with a mild polyarticular disease in humans. recent isolation of genetically diverse viruses within this group has prompted analysis of their genetic and phenotypic relationships. phylogenetic analysis based on complete orf, the envelope gene or the ns5/3' untranslated region supported the separation of the gro ... | 2013 | 23426358 |
| the phylogenetic and evolutionary history of kokobera virus. | to estimate the genetic diversity of kokobera virus, the date of origin and the spread among different viruses in the endemic regions of australia. | 2016 | 27794390 |
| natural exposure of horses to mosquito-borne flaviviruses in south-east queensland, australia. | in 2011 an unprecedented epidemic of equine encephalitis occurred in south-eastern (se) australia following heavy rainfall and severe flooding in the preceding 2-4 months. less than 6% of the documented cases occurred in queensland, prompting the question of pre-existing immunity in queensland horses. a small-scale serological survey was conducted on horses residing in one of the severely flood-affected areas of se-queensland. using a flavivirus-specific blocking-elisa we found that 63% (39/62) ... | 2013 | 24048209 |
| safety and immunogenicity of a delta inulin-adjuvanted inactivated japanese encephalitis virus vaccine in pregnant mares and foals. | in 2011, following severe flooding in eastern australia, an unprecedented epidemic of equine encephalitis occurred in south-eastern australia, caused by murray valley encephalitis virus (mvev) and a new variant strain of kunjin virus, a subtype of west nile virus (wnvkun). this prompted us to assess whether a delta inulin-adjuvanted, inactivated cell culture-derived japanese encephalitis virus (jev) vaccine (je-advax™) could be used in horses, including pregnant mares and foals, to not only indu ... | 2014 | 25516480 |