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transmission of hepatitis g virus in patients with angioedema treated with steam-heated plasma concentrates of c1 inhibitor.hepatitis g virus (hgv) is a blood-borne flavivirus that may cause acute and chronic transfusion-transmitted infections. patients with complement component 1 (c1) inhibitor (c1-inh) deficiency may acquire blood-borne infections through infusion of plasma concentrates.19989563413
[tick-borne encephalitis--etiopathogenesis and implications for public health in poland].tick-borne encephalitis (tbe) belongs to infectious units being under study in poland since over 40 years: clinical, virological, immunological, epidemiological (see eg. fig. 1 of the review) observations succeeded in developing tbe map of poland, and organization of satisfactory diagnostic virological control of the disease. this article covers most important data since the early (1952-1953) expeditions to the endemic districts of poland, studies of human beings, animal reservoir, both wild and ...19989608228
[japanese encephalitis: an exceptional imported arbovirus]. 19989779048
hepatitis g virus and related flaviviruses: pathogens or passengers? 19989779360
subcellular localization and some biochemical properties of the flavivirus kunjin nonstructural proteins ns2a and ns4a.in a previous study on the replication of kunjin virus using immunoelectron microscopy (e. g. westaway, j. m. mackenzie, m. t. kenney, m. k. jones, and a. a. khromykh, 1997, j. virol. 71, 6650-6661), ns1 and ns3 were found associated with double-stranded rna (dsrna) within vesicle packets (vp) in infected vero cells, suggesting that these induced membrane structures may be the cytoplasmic sites of rna replication. ns2b and ns3 (comprising the virus-encoded protease) were colocalized within disti ...19989636360
high prevalence of gb virus c/hepatitis g virus infection among homosexual men infected with human immunodeficiency virus type 1: evidence for sexual transmission.gb virus c/hepatitis g virus (gbv-c/hgv), a recently discovered orphan flavivirus, is distantly related to hepatitis c virus (hcv). although both gbv-c/hgv and hcv can be transmitted by the parenteral route, their principal modes of transmission and associated risk behaviors may differ. using reverse transcription-polymerase chain reaction, the 5'-noncoding regions of gbv-c/hgv and hcv were amplified from plasma or sera of 209 individuals infected with human immunodeficiency virus type 1 (hiv-1) ...19989746067
nucleic acid vaccines against hepatitis viruses.direct dna intramuscular or intradermal injection of plasmids containing viral genes under the control of viral promoters is an efficient means of stimulating both class i and class ii-mediated antiviral responses. viral hepatitis b and c are suitable candidates for this approach, particularly as therapeutic immunogens for chronically infected individuals. several groups have shown that the s gene of hbv is expressed in murine muscle and stimulates a high titre and long-lasting anti-hbs response ...19989554270
predominance of hla-restricted cytotoxic t-lymphocyte responses to serotype-cross-reactive epitopes on nonstructural proteins following natural secondary dengue virus infection.we examined the memory cytotoxic t-lymphocytic (ctl) responses of peripheral blood mononuclear cells (pbmc) obtained from patients in thailand 12 months after natural symptomatic secondary dengue virus infection. in all four patients analyzed, ctls were detected in bulk culture pbmc against nonstructural dengue virus proteins. numerous cd4+ and cd8+ ctl lines were generated from the bulk cultures of two patients, kpp94-037 and kpp94-024, which were specific for ns1.2a (ns1 and ns2a collectively) ...19989557687
immunological basis for protection in a murine model of tick-borne encephalitis by a recombinant adenovirus carrying the gene encoding the ns1 non-structural protein.the humoral immune response to flaviviruses is mainly directed to the major envelope protein, e, and a glycosylated non-structural protein, ns1. cell-mediated immune responses, however, appear to be directed mainly against non-structural proteins. experiments described here show that a defective recombinant adenovirus (rad51) containing the gene encoding the ns1 protein of tick-borne encephalitis virus can induce a strong protective immune response against several pathogenic tick-borne flaviviru ...19989568962
definition of the region on ns3 which contains multiple epitopes recognized by dengue virus serotype-cross-reactive and flavivirus-cross-reactive, hla-dpw2-restricted cd4+ t cell clones.the epitopes recognized by six cd4+ cd8- cytotoxic t lymphocyte (ctl) clones established from a dengue-3 virus-immune donor were defined. (i) three ctl clones, jk10, jk34 and jk39, were cross-reactive for dengue virus types 1-4. (ii) one clone, jk28, was cross-reactive for dengue virus types 1-4 and west nile virus. (iii) two clones, jk26 and jk49, were cross-reactive for dengue virus types 1-4, west nile virus and yellow fever virus. the clones, except for jk49, recognized the same epitope on n ...19989568963
mutation in a 17d-204 vaccine substrain-specific envelope protein epitope alters the pathogenesis of yellow fever virus in mice.the heterogeneous nature of the yellow fever (yf) 17d-204 vaccine virus population was exploited in this study to isolate virus variants able to escape neutralization by the 17d-204 vaccine-specific mab 864. the conformational change on the virus surface that resulted in the loss of the mab 864-defined epitope was effected in each variant by a single amino acid mutation in the envelope (e) protein at either position e-305 or e-325. interestingly, both positions were mutated during attenuation of ...19989581778
definition of an epitope on ns3 recognized by human cd4+ cytotoxic t lymphocyte clones cross-reactive for dengue virus types 2, 3, and 4.the role of dengue virus-specific serotype-cross-reactive t lymphocytes in recovery from and pathogenesis of dengue virus infections is not known. in the present paper, we have defined a dengue serotype-cross-reactive epitope recognized by two cd4+ cd8- cytotoxic t lymphocyte (ctl) clones, jk36 and jk46. these t cell clones were established from the peripheral blood t lymphocytes of a dengue-3-immune donor, using a limiting dilution method. jk36 and jk46 were cross-reactive for dengue virus type ...19989454689
[preparation and properties of monoclonal antibodies to tick-borne encephalitis viral nonstructural proteins].hybridomas secreting monoclonal antibodies (mab) to tick-borne encephalitis (tbe) virus are obtained. immunodiffusion showed that 3 mabs to tbe protein ns3 belong to class igm and the rest to igg1. mabs to tbe protein ns1 were tested in hemagglutination inhibition, complement fixation, neutralization, and protection tests. only 1 hybridoma produced mab specific for protein ns1 of tbe strain sofyin, the rest reacted with the common antigenic determinants of nonstructural tbe complex.19989702814
signal peptidase cleavage at the flavivirus c-prm junction: dependence on the viral ns2b-3 protease for efficient processing requires determinants in c, the signal peptide, and prm.signal peptidase cleavage at the c-prm junction in the flavivirus structural polyprotein is inefficient in the absence of the cytoplasmic viral protease, which catalyzes cleavage at the cooh terminus of the c protein. the signal peptidase cleavage occurs efficiently in circumstances where the c protein is deleted or if the viral protease complex is present. in this study, we used cdna of murray valley encephalitis virus (mve) to examine features of the structural polyprotein which allow this reg ...19989499070
spontaneous and engineered deletions in the 3' noncoding region of tick-borne encephalitis virus: construction of highly attenuated mutants of a flavivirus.the flavivirus genome is a positive-strand rna molecule containing a single long open reading frame flanked by noncoding regions (ncr) that mediate crucial processes of the viral life cycle. the 3' ncr of tick-borne encephalitis (tbe) virus can be divided into a variable region that is highly heterogeneous in length among strains of tbe virus and in certain cases includes an internal poly(a) tract and a 3'-terminal conserved core element that is believed to fold as a whole into a well-defined se ...19989499069
dna immunization with japanese encephalitis virus nonstructural protein ns1 elicits protective immunity in mice.japanese encephalitis virus (jev), a mosquito-borne flavivirus, is a zoonotic pathogen that is prevalent in some southeast asian countries and causes acute encephalitis in humans. to evaluate the potential application of gene immunization to jev infection, we characterized the immune responses from mice intramuscularly injected with plasmid dna encoding jev glycoproteins, including the precursor membrane (prm) plus envelope (e) proteins and the nonstructural protein ns1. when injected with the p ...19989420215
a rapid fluorescent focus inhibition test for detection of neutralizing antibodies to tick-borne encephalitis virus.tick borne encephalitis (tbe), is endemic in several countries in central and northern europe, in the baltic states and in russia. vaccination has been shown to lower efficiently the number of cases of this potentially very serious disease. however, the possibility to assess the neutralizing antibody response after clinical disease or vaccination has been hampered by the lack of easy and specific tests. we developed a rapid fluorescent focus inhibition test (rffit) and compared it with a standar ...19989705177
detection in chimpanzees of a novel flavivirus related to gb virus-c/hepatitis g virus.infection with hepatitis g virus (hgv) or gb virus-c (gbv-c) is widely distributed in human populations. viruses related to gbv-c/hgv have been recovered from several new world primate species, including tamarins, owl monkeys and marmosets. to understand more about the relationship between gb viruses and their hosts, we used primers from the 5' non-coding (5'nc), non-structural 3 (ns3) and ns5 regions in nested polymerase chain reactions to screen for related viruses infecting non-captive chimpa ...19989714234
characterization of defective viral rna produced during persistent infection of vero cells with murray valley encephalitis virus.defective interfering viral particles are readily produced in cell culture after a high multiplicity of infection with many animal rna viruses. due to defects that they carry in their genomes, their life cycle needs to be complemented by the helper functions provided by a parental virus which makes them both dependent on and competitive with the parental virus. in many instances, this may cause the abrogation of a lytic cycle of the parental virus, leading to a persistent infection. in this pape ...19989499109
evaluation of recombinant dengue viral envelope b domain protein antigens for the detection of dengue complex-specific antibodies.to increase the specificity of dengue (den) diagnosis based on antibody detection, we have evaluated recombinant proteins as antigens that incorporate most of the b domain of the den virus envelope protein fused to the trpe protein of escherichia coli (trpe-den). a pooled antigen consisting of trpe-den proteins representing all four serotypes of den virus was used in an indirect elisa for the detection of igg or igm antibody. this assay was compared with a standard igg indirect elisa and an igm- ...19989502595
tumor necrosis factor alpha levels in plasma and whole-blood culture in dengue-infected patients: relationship between virus detection and pre-existing specific antibodies.the pathogenesis of dengue hemorrhagic fever (dhf) is not well known, but the role of host factors has been suggested. the level of immunoreactive circulating and cell-generated tumor necrosis factor alpha (tnf alpha) was studied in 35 patients with dhf; its relationship with virus isolation and/or genome detection by reverse transcription polymerase chain reaction (rt-pcr) and specific antibodies were detected by hemagglutination inhibition (hi). large variation of tnf alpha plasma levels was o ...19989515771
west nile encephalitis epidemic in southeastern romania.west nile fever (wnf) is a mosquito-borne flavivirus infection endemic in africa and asia. in 1996, the first major wnf epidemic in europe occurred in romania, with a high rate of neurological infections. we investigated the epidemic to characterise transmission patterns in this novel setting and to determine its origin.19989737281
determination of dengue virus serotypes in individual aedes aegypti mosquitoes in colombia.adult aedes aegypti mosquitoes were collected in puerto triunfo, central colombia, where dengue is endemic, during a six month period. viral infection within the head of each individual mosquito was identified by an immunofluorescent assay (ifa) using a flavivirus-specific monoclonal antibody. the dengue virus serotype, present in each flavivirus-positive specimen, was then determined in portions of the remaining thorax using ifas with serotype-specific monoclonal antibodies. among 2065 female a ...19989737600
immune mediated and inherited defences against flaviviruses.flavivirus infection elicits an abundant immune response in the host which is directed against a number of the viral proteins. resistance to flavivirus-induced disease can also be controlled via a non-immune mechanism involving the product of a naturally occurring murine gene, flv.19989741638
the conformation of hepatitis c virus ns3 proteinase with and without ns4a: a structural basis for the activation of the enzyme by its cofactor.hepatitis c virus (hcv) ns3 proteinase activity is required for the release of hcv nonstructural proteins and is thus a potential antiviral target. the enzyme requires a protein cofactor ns4a, located downstream of ns3 on the polyprotein, for activation and efficient processing.19989741640
genetically determined resistance to flavivirus infection in wild mus musculus domesticus and other taxonomic groups in the genus mus.inherited resistance to flaviviruses in laboratory mice is a rare trait conferred by an autosomal dominant gene (flvr). to provide information on genetic resistance to flaviviruses in wild mice, we analysed (i) wild m. m. domesticus trapped in australia, and (ii) mice representing other species and subspecies in the genus mus. mice were screened for resistance relative to c3h/hej mice by intracerebral challenge with murray valley encephalitis virus or yellow fever virus, and breeding studies wer ...19989638142
[protein e 98-113 sequence is a fusion site of tick-borne encephalitis virus with cellular membrane].the synthetic peptide with the conservative 98-113 sequence of protein e of tick-borne encephalitis virus was studied in order to elucidate its role in the functioning of flaviviruses. the peptide was shown to inhibit the in vitro infection of macrophages with the virus. an antibody that specifically binds this peptide was found among the set of monoclonal antibodies produced against protein e. this antibody was found to prevent penetration of the virus into liposomes. a correlation was found be ...19989813732
genetic control of host resistance to flavivirus infection in animals.flaviviruses are small, enveloped rna viruses which are generally transmitted by arthropods to animals and man. although flaviviruses cause important diseases in domestic animals and man, flaviviral infection of animals which constitute the normal vertebrate reservoir may be mild or sub-clinical, which suggests that some adaptation between virus and host may have occurred. while this possibility is difficult to study in wild animals, extensive studies using laboratory mice have demonstrated the ...19989638813
growth restriction of dengue virus type 2 by site-specific mutagenesis of virus-encoded glycoproteins.the three flavivirus glycoproteins prm, e and ns1 are formed by post-translational cleavage and are glycosylated by the addition of n-linked glycans. ns1 may form homodimers, whereas e may form homodimers, homotrimers or heterodimers (prm-e). modification of these processes by mutagenesis of the proteins has the potential to generate viruses that are restricted in growth and are possible vaccine candidates. using an sv40-based expression system, we previously analysed dimerization and secretion ...19989820138
prevalence of hepatitis g-virus infection in alcohol abusing patients with and without liver cirrhosis.hepatitis g (gbv-c/hgv) is an rna-virus belonging to the flavivirus family and is capable of inducing hepatitis in rare cases. its importance as a co-factor in the pathogenesis of liver disease needs to be clarified.19989823622
critical point mutations for hepatitis c virus ns3 proteinase.the hepatitis c virus ns3 proteinase plays an essential role in processing of hcv nonstructural precursor polyprotein. to detect its processing activity, we developed a simple trans-cleavage assay. two recombinant plasmids expressing the ns3 proteinase region and a chimeric substrate polyprotein containing the ns5a/5b cleavage site between maltose binding protein and protein a were co-introduced into escherichia coli cells. the proteinase processed the substrate at the single site during their p ...19989656998
monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus, jamaica.although dengue (den) virus is the etiologic agent of dengue fever, the most prevalent vector-borne viral disease in the world, precise information on the antigenic structure of the dengue virion is limited. we have prepared a set of murine monoclonal antibodies (mabs) specific for the envelope (e) glycoprotein of den 2 virus and used these antibodies in a comprehensive biological and biochemical analysis to identify 16 epitopes. following domain nomenclature developed for the related flavivirus ...19989657950
in vitro-synthesized infectious rna as an attenuated live vaccine in a flavivirus model.live virus vaccines have in many cases proven to be an extremely effective tool for the prevention of viral diseases. however, the production of conventional live vaccines in eukaryotic cell cultures has many disadvantages, including the potential for contamination with adventitious agents and genetic alterations during propagation, making it necessary to do extensive testing before distribution. based on results obtained with a flavivirus (tick-borne encephalitis virus) in an experimental anima ...19989846585
recombinant dengue virus type 1 ns3 protein exhibits specific viral rna binding and ntpase activity regulated by the ns5 protein.the full-length dengue virus ns3 protein has been successfully expressed as a 94-kda gst fusion protein in escherichia coli. treatment of the purified fusion protein with thrombin released a 68-kda protein which is the expected molecular mass for the den1 ns3 protein. the identity of this protein was confirmed by western blotting using dengue virus antisera. two related activities of the recombinant ns3 protein were characterized, which were the binding of the protein to the 3'-noncoding region ...19989657959
vaccination against tick-borne encephalitis virus, a flavivirus, prevents disease but not infection, although viremia is undetectable.by adoptive transfer of sera or immunoglobulin preparations, vaccine-induced protection against tbev has been demonstrated to be mediated by antibodies to the surface protein of tbev, glycoprotein e. nevertheless, the mechanism of vaccine-induced protection against tbev remains unclear. protection by e antibodies without in vitro neutralization was shown by one group, whereas others found a correlation between protection in vivo and neutralization in vitro. here, the authors confirm in a mouse m ...19989682362
yellow fever 17d vaccine virus isolated from healthy vaccinees accumulates very few mutations.the live attenuated yellow fever (yf) vaccine strain 17d is one of the safest vaccines in use today with only 22 cases of reversion to virulence documented from over 300 million doses administered. we have isolated virus in cell culture from sera of six volunteers who received 17d vaccine and found that very few nucleotide mutations were detected in the consensus sequence of the entire genome of each of the serum viruses. moreover, most of these mutations accumulated in the non-structural protei ...19989712515
japanese encephalitis. 19989876271
design of selective eglin inhibitors of hcv ns3 proteinase.hepatitis c virus (hcv) infection is a major health problem that leads to cirrhosis and hepatocellular carcinoma in a substantial number of infected individuals, estimated to be 100-200 million worldwide. unfortunately, immunotherapy or other effective treatments for hcv infection are not yet available, and interferon administration has limited efficacy. different approaches to hcv therapy are being explored, and these include inhibition of the viral proteinase, helicase, and rna-dependent rna p ...19989708981
the metal binding site of the hepatitis c virus ns3 protease. a spectroscopic investigation.the ns3 region of the hepatitis c virus encodes for a serine protease activity, which is necessary for the processing of the nonstructural region of the viral polyprotein. the minimal domain with proteolytic activity resides in the n terminus, where a structural tetradentate zinc binding site is located. the ligands being been identified by x-ray crystallography as being three cysteines (cys97, cys99, and cys145) and one histidine residue (his149), which is postulated to coordinate the metal thr ...19989668049
mutation in ns5 protein attenuates mouse neurovirulence of yellow fever 17d vaccine virus.the 17d-204 vaccine manufactured in south africa (17d-204-sa) and a large plaque variant (17d-lp) derived from it were highly virulent in adult mice. the ld50 of 17d-lp virus was 0-2 p.f.u. for mice following intracerebral inoculation. in comparison, a medium plaque variant derived from 17d-lp, termed 17d-mp virus, was found to be attenuated in adult mice following the same route of inoculation (> 10(4) p.f.u./ld50). replication of 17d-mp virus was decreased in infected mouse brains compared to ...19989714237
prevalence and patterns of hgv/gbv-c infection in patients with suspected hcv-related hepatitis.hepatitis g virus (hgv) is a recently described hepatotropic parenterally transmitted flavivirus. the presence of hgv was tested in 61 patients with a request for confirmation of hcv active infection. thirty-two patients were in haemodialysis and 29 were referred from wards other than nephrology. active hcv and hgv infections were determined by detection of their viral rna in serum. evaluation of previous hgv infection was carried out by detection of antibodies to e2 antigen. hcv prevalence was ...19989923019
hepatitis g virus infection in lymphoma and in blood donors.to determine whether the recently described flavivirus, hepatitis g virus (hgv), might contribute to the pathogenesis of lymphoma by testing for the presence of hgv rna in sera from patients attending lymphoma clinics; to compare the incidence of hgv rna in lymphoma patients with that in normal blood donors; and to look for potential risk factors for hgv infection and for evidence of hepatic disease in the hgv positive patients.19989930072
trans-complementation of flavivirus rna polymerase gene ns5 by using kunjin virus replicon-expressing bhk cells.a bhk cell line persistently expressing a kunjin (kun) virus replicon rna (repbhk, similar to our recently described me/76neo bhk cell line [a. a. khromykh and e. g. westaway, j. virol. 71:1497-1505, 1997]) was used for rescue and propagation of kun viruses defective in the rna polymerase gene (ns5). a new infectious full-length kun virus cdna clone, flsdx, prepared from our previously described cdna clone pakun (a. a. khromykh and e. g. westaway, j. virol. 68:4580-4588, 1994) and possessing app ...19989696822
identification of specific nucleotide sequences within the conserved 3'-sl in the dengue type 2 virus genome required for replication.the flavivirus genome is a positive-stranded approximately 11-kb rna including 5' and 3' noncoding regions (ncr) of approximately 100 and 400 to 600 nucleotides (nt), respectively. the 3' ncr contains adjacent, thermodynamically stable, conserved short and long stem-and-loop structures (the 3'-sl), formed by the 3'-terminal approximately 100 nt. the nucleotide sequences within the 3'-sl are not well conserved among species. we examined the requirement for the 3'-sl in the context of dengue virus ...19989696848
[prevalence of flavivirus antibodies in young voluntary recruits to military service in the province of formosa, argentina].the aim of the present study was to investigate the seroprevalence to flavivirus, in young people living in risk areas. we analyzed 189 human sera from 3 towns in the province of formosa. this area corresponds to the border that limits brasil and paraguay and the aim was to search for a possible introduction of dengue and yellow fever from these countries. serological tests such as haemagglutination inhibition (hi), complement fixation (cf) and neutralization (nt) were performed using st. louis ...19989950038
epidemiology of the hepatitis c virus.according to who estimations, about 3% of the world population may be infected with the hepatitis c virus. the relative prevalences of subtypes of this virus vary in different geographic areas. the main known routes of transmission are parenteral; intravenous drug abuse, contaminated injection devices and receipt of unscreened blood. sexual, vertical, household and nosocomial transmissions may occur, but seem to be rare. the risk of screened blood or blood products is now almost eliminated, but ...19989704437
evaluation of a rapid immunochromatographic test for diagnosis of dengue virus infection.a rapid (<7-min) immunochromatographic test for immunoglobulin m (igm) and igg antibodies to dengue viruses was evaluated by using hospital admission and discharge sera from 124 patients. the reference laboratory diagnosis was based on the results of virus isolation, hemagglutination-inhibition assay (hai), and enzyme immunoassay (eia). by the standard assays, patients experienced primary dengue virus infection (n = 30), secondary dengue virus infection (n = 48), japanese encephalitis (je) virus ...19989431954
neutralizing antibodies protect against lethal flavivirus challenge but allow for the development of active humoral immunity to a nonstructural virus protein.antibody-mediated neutralization of viruses has been extensively studied in vitro, but the precise mechanisms that account for antibody-mediated protection against viral infection in vivo still remain largely uncharacterized. the two points under discussion are antibodies conferring sterilizing immunity by neutralizing the virus inoculum or protection against the development of disease without complete inhibition of virus replication. for tick-borne encephalitis virus (tbev), a flavivirus, trans ...19989525632
emerging viruses.an emerging virus is a term applied to a newly discovered virus, one that is increasing in incidence or with the potential to increase in incidence. many viruses fit into this definition. hiv is the clearest example of a previously unknown virus that has now produced one of the largest pandemics in history. recent advances have occurred in the identification and understanding of new hantaviruses in the americas, causing an acute respiratory disease. the possible causal role of human herpesvirus ...19989529635
antibodies to alphavirus, flavivirus, and bunyavirus arboviruses in house sparrows (passer domesticus) and tree sparrows (p. montanus) in poland.sparrows from central poland were examined by a hemagglutination-inhibition test (titer > or = 20) for the presence of antibodies to arboviruses, between 1995 and 1996. in house sparrows (passer domesticus) (n = 179), antibodies to sindbis, west nile, tick-borne encephalitis, tahyna, and calovo viruses were detected at seroprevalences of 1.1%, 2.8%, 1.1%, 2.8%, and 1.1%, respectively. in tree sparrows (p. montanus) (n = 33), antibodies to the sindbis, west nile, and tahyna viruses were detected ...19989533098
hcv and hgv in b-cell non-hodgkin's lymphoma.a causative role of hepatitis c virus infection (hcv) has been discussed in the pathogenesis of mixed cryoglobulinaemia and in b-cell non-hodgkin's lymphoma. no data are available concerning the newly discovered hepatitis g virus (hgv) and extrahepatic manifestations such as haematological malignancies. but, hcv and hgv most probably belong to the same family of flavivirus. consequently, we looked for the prevalence of hcv, hgv and cryoglobulins in patients with b-cell non-hodgkin's lymphoma.19989537861
inhibitory effect of furanonaphthoquinone derivatives on the replication of japanese encephalitis virus.japanese encephalitis still occurs in endemic and epidemic forms over a wide area of asia. although the vaccine against japanese encephalitis virus (jev) is widely used, no antiviral drug has been reported. we used several different kinds of furanonaphthoquinone derivatives and found antiviral activity against jev. especially, 2-methylnaphtho[2,3-b]furan-4,9-dione (fnq3) indicated the highest antiviral activity, followed by 2-(1-hydroxyethyl)-, 5(or 8)-hydroxy-, and 2-methyl-5(or 8)-hydroxy-anal ...19989497071
dengue fever epidemic potential as projected by general circulation models of global climate change.climate factors influence the transmission of dengue fever, the world's most widespread vector-borne virus. we examined the potential added risk posed by global climate change on dengue transmission using computer-based simulation analysis to link temperature output from three climate general circulation models (gcms) to a dengue vectorial capacity equation. our outcome measure, epidemic potential, is the reciprocal of the critical mosquito density threshold of the vectorial capacity equation. a ...19989452414
hepatic histology in hepatitis c virus carriers coinfected with hepatitis g virus.a novel flavivirus has been described recently and designated hepatitis g virus (hgv). the virus is transmitted by the parenteral route but it is uncertain whether it is associated with chronic liver disease because liver biopsy is difficult to justify in this group.19989505894
african origin of gb virus c/hepatitis g virus.ninety-four gb virus c/hepatitis g virus (gbv-c/ hgv) rna-positive serum samples were obtained from all over the world. we found that all 15 gbv-c/hgv isolates from the pygmies and the bantu in the central african region had a 12-amino acid indel (i.e. insertion or deletion) in the non-structural protein (ns) 5a region. phylogenetic analyses of the ns5a region, using gbv-a as an outgroup, showed that these 15 isolates had diverged from the common ancestor much earlier than the remaining isolates ...19989512347
fulminant hepatitis and the new g/gbv-c flavivirus.a new virus within the family flaviviridae. 'hepatitis' g/gbv-c, has been incriminated by several authors as a causative factor of idiopathic or cryptogenic fulminant hepatitis, a syndrome of presumed viral aetiology. review of worldwide data from 22 studies on 364 cases indicates that g/gbv-c infection is present in approximately 20% of idiopathic cases but a similar or even higher prevalence is detected in fulminant hepatitis of viral b, d or c aetiology, reflecting a high rate of parenteral v ...19989493512
patterns of hepatitis g viraemia and liver disease in haemophiliacs previously exposed to non-virus inactivated coagulation factor concentrates.hepatitis g virus (hgv), a novel flavivirus, has been implicated as a cause of posttransfusion hepatitis. we have performed a longitudinal study in a cohort of haemophiliacs (n = 68) who previously received non-virus inactivated coagulation factor concentrates to assess both patterns of hgv viraemia and any associated liver disease. hepatitis c virus (hcv) rna was present in 58/68 and co-infection with human immunodeficiency virus (hiv) was present in 15/68. hgv rna was detected in 17/68 (25%) s ...19989493578
conversion of dengue virus replicative form rna (rf) to replicative intermediate (ri) by nonstructural proteins ns-5 and ns-3.dengue viruses infect more than 100 million people each year and cause serious clinical manifestations. it is important to understand the replication of these viruses so that therapeutic and/or prophylactic agents may be designed. dengue virus type 2 nonstructural proteins ns-5 and ns-3 were produced by in vitro transcription and translation of cloned genes. both proteins possessed rna-dependent rna polymerase activity as measured by their ability to convert purified replicative form (rf) rna to ...19989452298
gb virus c/hepatitis g virus infection in hemodialysis patients: determination of seroprevalence by a four-antigen recombinant immunoblot assay.gb virus c/hepatitis g virus (gbv-c/hgv) was identified recently and only two assays, consisting of a single recombinant protein, have been described for determination of the seroprevalence of this virus. an immunoblot assay was devised, which contains four recombinant gbv-c/hgv proteins. in this study, serum samples from 154 patients on maintenance hemodialysis were examined to assess the rate of seroreactivity against gbv-c/hgv. all sera were tested for the presence of antibodies by an in-hous ...199910022792
sequence heterogeneity within three different regions of the hepatitis g virus genome.two sets of primers derived from the 5'-terminal region and the ns5 region of the hepatitis g virus (hgv) genome were used to amplify pcr fragments from serum specimens obtained from different parts of the world. all pcr fragments from the 5'-terminal region (5'-pcr, n = 56) and from the ns5 region (ns5-pcr, n = 85) were sequenced and compared to corresponding published hgv sequences. the range of nucleotide sequence similarity varied from 74 and 78% to 100% for 5'-pcr and ns5-pcr fragments, res ...199910069950
noncytopathic flavivirus replicon rna-based system for expression and delivery of heterologous genes.noncytopathic replicons of the flavivirus kunjin (kun) were employed for expression and delivery of heterologous genes. replicon vector c20dx2arep, containing a unique cloning site followed by the sequence of 2a autoprotease of foot-and-mouth disease virus, was constructed and used for expression of a number of heterologous genes including chloramphenicol acetyltransferase (cat), green fluorescent protein (gfp), beta-galactosidase, glycoprotein g of vesicular stomatitis virus, and the core and n ...199910069962
a phylogenetically conserved stem-loop structure at the 5' border of the internal ribosome entry site of hepatitis c virus is required for cap-independent viral translation.hepatitis c virus (hcv) initiates translation of its polyprotein under the control of an internal ribosome entry site (ires) that comprises most of the 341-nucleotide (nt) 5' nontranslated rna (5'ntr). a comparative analysis of related flaviviral sequences suggested that an rna segment for which secondary structure was previously ill defined (domain ii, nt 44 to 118) forms a conserved stem-loop that is located at the 5' border of the hcv ires and thus may function in viral translation. this pred ...19999882318
molecular characterization of the 5' non-coding region of south african gbv-c/hgv isolates: major deletion and evidence for a fourth genotype.gb virus c/hepatitis g virus (gbv-c/hgv) has been characterised as a novel flavivirus, and to date three known genotypes have been cloned. greater genetic variation of gbv-c/hgv has been demonstrated in west african isolates, but no major deletions have been shown in the 5' non-coding region (ncr). the 5'ncr regulates protein translation via an internal ribosomal entry site (ires). we cloned, sequenced, and analysed a 344-bp polymerase chain reaction (pcr) product, representing >60% of the 5'ncr ...199910440808
mutant influenza viruses with a defective ns1 protein cannot block the activation of pkr in infected cells.a short model genome rna and also the genome rna of influenza a virus bearing both 5'- and 3'-terminal common sequences activated the interferon-induced double-stranded-rna-dependent protein kinase, pkr, by stimulating autophosphorylation in vitro. the activated pkr catalyzed phosphorylation of the alpha subunit of eucaryotic translation initiation factor 2 (eif2alpha). the ns1 protein efficiently eliminated the pkr-activating activity of these rnas by binding to them. two mutant ns1 proteins, e ...19999971827
partial agonist effect influences the ctl response to a heterologous dengue virus serotype.activation of dengue serotype-cross-reactive memory ctl during secondary dengue virus (dv) infection is thought to be important in the pathogenesis of dengue hemorrhagic fever. to model this effect, we studied the ctl responses to dv types 2 (d2v) and 3 (d3v) in pbmc from an individual previously infected with d3v. dv-specific cd8+ ctl from this donor recognized two hla-b62-restricted epitopes on the ns3 protein, aa 71-79 (svkkdlisy) and 235-243 (amkglpiry). both d3v-specific and d2v/d3v-cross-r ...199910453018
a focus of deer tick virus transmission in the northcentral united states.we screened salivary glands from adult deer ticks collected near spooner and hayward, wisconsin, to determine whether deer tick virus, a recently described flavivirus, occurs with other tickborne agents in the upper midwest. intraacinar inclusions suggestive of replicating virus were detected in 4 (4.6%) of 87 ticks. the virus was isolated by suckling-mouse inoculation.199910460180
fatal dengue hemorrhagic fever in cuba, 1997.after more than 15 years without dengue activity, a dengue ii epidemic was reported in cuba in 1997. three thousand and twelve serologically confirmed cases were reported, with 205 dengue hemorrhagic fever/dengue shock syndrome (dhf/dss) cases and 12 fatalities. this report presents the clinical, serologic, and virologic findings in the 12 fatal dhf/dss cases.199910460923
dengue virus ns3 serine protease. crystal structure and insights into interaction of the active site with substrates by molecular modeling and structural analysis of mutational effects.the mosquito-borne dengue viruses are widespread human pathogens causing dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, placing 40% of the world's population at risk with no effective treatment. the viral genome is a positive strand rna that encodes a single polyprotein precursor. processing of the polyprotein precursor into mature proteins is carried out by the host signal peptidase and by ns3 serine protease, which requires ns2b as a cofactor. we report here the crystal str ...199910026173
sequence analysis and genetic classification of tick-borne encephalitis viruses from europe and asia.the epidemiology of tick-borne encephalitis virus was investigated by comparative sequence analysis of virus strains isolated in endemic areas of europe and asia. phylogenetic relationships were determined from the nucleotide and amino acid sequences of the major envelope (e) protein of 16 newly sequenced strains and nine previously published sequences. three genetic lineages could be clearly distinguished, corresponding to a european, a far eastern and a siberian subtype. amino acids characteri ...19999934700
analysis of murine cd8(+) t-cell clones specific for the dengue virus ns3 protein: flavivirus cross-reactivity and influence of infecting serotype.serotype-cross-reactive dengue virus-specific cytotoxic t lymphocytes (ctl) induced during a primary dengue virus infection are thought to play a role in the immunopathogenesis of dengue hemorrhagic fever (dhf) during a secondary dengue virus infection. although there is no animal model of dhf, we previously reported that murine dengue virus-specific ctl responses are qualitatively similar to human dengue virus-specific ctl responses. we used balb/c mice to study the specificity of the ctl respo ...19999847344
partial nucleotide sequencing of the ns3/helicase region of hepatitis g virus to prove vertical transmission.to study non-parental transmission of hepatitis g virus and/or gb virus c (hgv/gbv-c), we sequenced and compared the ns3/helicase region of the virus for five hgv/gbv-c rna-positive mothers and their 11 children who had experienced neither blood transfusion nor overt hepatitis and were negative for hbv, hcv and hiv, except in one mother coinfected with hcv. the nucleotide sequences of the familial hgv/gbv-c isolates showed high similarity of 99-100% (mean 99.8%, 100% at the deduced amino acid le ...199910386379
molecular evidence of mother-to-infant transmission of hepatitis g virus among women without known risk factors for parenteral infections.hepatitis g virus (hgv) rna was detected in 18 of 133 pregnant women from tanzania without known risk factors for hgv infection and in 7 of 18 children born to hgv rna-positive mothers. molecular evidence of mother-to-infant transmission was obtained only for three of seven children. hgv rna was also detected in 4 of 42 children born to non-hgv-infected women. thus, mechanisms other than materno-filial may play an important role in hgv transmission during early childhood.199910364608
mutation patterns for two flaviviruses: hepatitis c virus and gb virus c/hepatitis g virus.we studied the mutation patterns of hepatitis c virus (hcv) and gb virus c/hepatitis g virus (hgv). although the mutation patterns of the two viruses were similar to each other, they were quite different from that of hiv. in particular, the similarity of the patterns between hcv or hgv and human nuclear pseudogenes was statistically significant whereas there was no similarity between hiv and human nuclear pseudogenes. this finding suggests that the mutation patterns of hcv and hgv are similar to ...199910359092
homology model of the dengue 2 virus ns3 protease: putative interactions with both substrate and ns2b cofactor.the crystal structure coordinates of the hepatitis c virus ns3 protease (hcvpro) were used to develop an homology model of the dengue 2 virus ns3 protease (den2pro). the amino acid sequence of den2pro accommodates the same alpha-helices, beta-sheets and protein-binding domains as its hcvpro counterpart, but the model predicts a number of significant differences for den2pro and its interactions with substrates and cofactor. whereas hcvpro contains a zn2+-binding site, there is no equivalent metal ...199910355763
recombinant, chimaeric live, attenuated vaccine (chimerivax) incorporating the envelope genes of japanese encephalitis (sa14-14-2) virus and the capsid and nonstructural genes of yellow fever (17d) virus is safe, immunogenic and protective in non-human primates.yellow fever 17d virus, a safe and effective live, attenuated vaccine, was used as a vector for genes encoding the protective antigenic determinants of a heterologous member of the genus flavivirus, japanese encephalitis (je) virus, the leading cause of acute viral central nervous system infection and death throughout asia. the viral envelope (prm and e) genes of a full-length cdna clone of yf 17d virus were replaced with the corresponding genes of je sa14-14-2, a strain licensed as a live, atte ...199910217584
prevalence of gbv c/hgv rna and gbv c/hgv antibodies in french volunteer blood donors: results of a collaborative study.posttransfusion hepatitis still occurs at an incidence of about 1 in 118,000 for hbv and 1 in 220,000 for hcv. this collaborative study aimed to determine the prevalence of a novel flavivirus, gbv-c/hgv, even though its role in transfusion-associated hepatitis is uncertain.199910341332
in vitro infection of human peripheral blood mononuclear cells by gb virus c/hepatitis g virus.gb virus c (gbv-c), also known as hepatitis g virus, is a recently discovered flavivirus-like rna agent with unclear pathogenic implications. to investigate whether human peripheral blood mononuclear cells (pbmc) are susceptible to in vitro gbv-c infection, we have incubated pbmc from four healthy blood donors with a human gbv-c rna-positive serum. by means of (i) strand-specific reverse transcription-pcr, cloning, and sequencing; (ii) sucrose ultracentrifugation and rnase sensitivity assays; (i ...199910196301
the clinical significance of simultaneous infection with hepatitis g virus in patients with chronic hepatitis c.hepatitis g virus (hgv) is a recently discovered member of the flavivirus family that has been associated with acute and chronic hepatitis. hgv infection has been reported to coexist in 10-20% of patients with chronic hepatitis c. the significance of simultaneous infection with hgv and hepatitis c virus (hcv) remains to be clarified, as do the effects on hgv of therapeutic interventions such as interferon treatment or liver transplantation. the aims of our study were: 1) to examine the frequency ...199910201473
use of a fluorescence plate reader for measuring kinetic parameters with inner filter effect correction.a general method is presented here for the determination of the km, kcat, and kcat/km of fluorescence resonance energy transfer (fret) substrates using a fluorescence plate reader. a simple empirical method for correcting for the inner filter effect is shown to enable accurate and undistorted measurements of these very important kinetic parameters. inner filter effect corrected rates of hydrolysis of a fret peptide substrate by hepatitis c virus (hcv) ns3 protease at various substrate concentrat ...199910036138
mosquito feeding modulates th1 and th2 cytokines in flavivirus susceptible mice: an effect mimicked by injection of sialokinins, but not demonstrated in flavivirus resistant mice.culex pipiens and aedes aegypti mosquitoes were fed on c3h/hej mice and systemic cytokine production was quantified from stimulated lymphocytes harvested four to ten days after feeding. mosquito feeding on c3h/hej mice significantly down regulated ifn gamma production seven to ten days post feeding by cx. pipiens and seven days after ae aegypti feeding. th2 cytokines, il-4 and il-10, were significantly up regulated 4-7 days after cx. pipiens and ae. aegypti feeding. the immunosuppressive effect ...199910081770
[yellow fever]. 199910088360
detection of gb virus c/hepatitis g virus rna by reverse-transcription polymerase chain reaction.recently, a novel rna virus, designated gb virus c or hepatitis g virus (gbv-c/hgv) has been identified which may possibly be associated with human hepatitis. in this study, the nucleotide sequences of the partial nonstructural 5 (ns5) gene of gbv-c/hgv derived from sera of eight chinese patients were determined. the overall degree of nucleotide conservation and the existence of regional highly conserved sequences make this part of the genome suitable for the development of diagnostic reagents. ...199910094376
preliminary studies on the use of solid-phase immunosorbent techniques for the rapid detection of wesselsbron virus (wslv) igm by haemagglutination-inhibition.serum samples from 446 randomly selected persons belonging to different age groups and locations in nigeria were tested for the presence of wslv igm using the flavivirus haemagglutination-inhibition (hi) test adopted to the solid-phase immunosorbent technique (spit). 61 (14%) persons had igm to wslv only, while 9 (2%) persons had heterologous igm to wslv and two other flaviviruses, namely yellow fever and uganda s viruses. there was a high prevalence of igm in people of younger age groups than t ...199910099030
[preparation of single-chained antibodies to surface glycoprotein e from tick-borne encephalitis virus].a single-stranded antibody gene scfv was designed on the base of cdna fragments of genes coding for variable domains of heavy and light chains of mab e6b to tick-borne encephalitis glycoprotein e. high production of stable soluble scfv was reproduced in escherichia coli cells. recombinant antibodies bound to antiidiotypical antibodies to initial mab e6b and to recombinant virus protein e. competitive analysis showed that single-stranded antibodies inhibited reaction between mab e6b and protein e ...199910190234
yellow fever/japanese encephalitis chimeric viruses: construction and biological properties.a system has been developed for generating chimeric yellow fever/japanese encephalitis (yf/je) viruses from cdna templates encoding the structural proteins prm and e of je virus within the backbone of a molecular clone of the yf17d strain. chimeric viruses incorporating the proteins of two je strains, sa14-14-2 (human vaccine strain) and je nakayama (je-n [virulent mouse brain-passaged strain]), were studied in cell culture and laboratory mice. the je envelope protein (e) retained antigenic and ...199910074160
the serine protease and rna-stimulated nucleoside triphosphatase and rna helicase functional domains of dengue virus type 2 ns3 converge within a region of 20 amino acids.ns3 protein of dengue virus type 2 has a serine protease domain within the n-terminal 180 residues. ns2b is required for ns3 to form an active protease involved in processing of the viral polyprotein precursor. the region carboxy terminal to the protease domain has conserved motifs present in several viral rna-stimulated nucleoside triphosphatase (ntpase)/rna helicases. to define the functional domains of protease and ntpase/rna helicase activities of ns3, full-length and amino-terminal deletion ...199910074162
[tick-encephalitis after a vacation in southern germany].a 38-year-old man was admitted with signs of meningoencephalitis. tick-borne encephalitis was considered because the patient reported a tick bite during a vacation in south germany and because of the biphasic course of the symptoms. serology for tick-borne encephalitis was positive: this constituted the first reported positive serology outcome in the national institute for public health and environment in the netherlands. tick-borne encephalitis is an infection with a flavivirus transmitted by a ...199910494331
nucleoside triphosphatase and rna helicase activities associated with gb virus b nonstructural protein 3.gb virus b (gbv-b) is a positive-stranded rna virus that belongs to the flaviviridae family. this virus is closely related to hepatitis c virus (hcv) and causes acute hepatitis in tamarins (saguinus species). nonstructural protein 3 (ns3) of gbv-b contains sequence motifs predictive of three enzymatic activities: serine protease, nucleoside triphosphatase (ntpase), and rna helicase. the n-terminal serine protease has been characterized and shown to share similar substrate specificity with the hc ...199910497107
[seroprevalence of central european tick-borne encephalitis in the lorraine region].central european encephalitis, caused by the tick-borne encephalitis virus (tbev), is exceptional in france. most cases have been described in alsace. as 2 cases of tick-borne encephalitis were diagnosed in the nancy region, a seroepidemiological survey was conducted in the lorraine region (meurthe & moselle, moselle, vosges, meuse) in 1996.199910076595
trans-complementation analysis of the flavivirus kunjin ns5 gene reveals an essential role for translation of its n-terminal half in rna replication.recently we described rescue of defective kunjin virus (kun) rnas with small deletions in the methyltransferase and rna polymerase motifs of the ns5 gene, using bhk cells stably expressing kun replicon rna (repbhk cells) as helper (a. a. khromykh et al., j. virol. 72:7270-7279, 1998). we have now extended our previous observations and report successful trans-complementation of defective kun rnas with most of the ns5 gene deleted or substituted with a heterologous (dengue virus) ns5 sequence. rep ...199910516033
markers for trans-golgi membranes and the intermediate compartment localize to induced membranes with distinct replication functions in flavivirus-infected cells.replication of the flavivirus kunjin virus is associated with virus-induced membrane structures within the cytoplasm of infected cells; these membranes appear as packets of vesicles associated with the sites of viral rna synthesis and as convoluted membranes (cm) and paracrystalline arrays (pc) containing the components of the virus-specified protease (e. g. westaway, j. m. mackenzie, m. t. kenney, m. k. jones, and a. a. khromykh, j. virol. 71:6650-6661, 1997). to determine the cellular origins ...199910516064
the 37-amino-acid interdomain of dengue virus ns5 protein contains a functional nls and inhibitory ck2 site.the dengue virus ns5 rna-dependent rna polymerase has been detected in the nucleus of virus-infected mammalian cells. we demonstrate here for the first time using in vitro and in vivo assay systems that the 37-amino-acid linker interdomain of ns5 (residues 369 to 405) contains a nuclear localization sequence (nls) which is capable of targeting b-galactosidase to the nucleus. further, we show that the linker is recognized by subunits of the nls-binding importin complex with an affinity similar to ...199910208852
development and characterization of new flavivirus-resistant mouse strains bearing flv(r)-like and flv(mr) alleles from wild or wild-derived mice.a single genetic locus, flavivirus resistance (flv), controls virus titres and severity of flavivirus infection in mouse brain. it has been mapped to mouse chromosome 5 and shown to include different allelic forms. while the majority of laboratory mouse strains are susceptible to flaviviruses and carry the flv(s) allele, wild mice and laboratory mouse strains recently derived from them are resistant and carry flavivirus-resistance alleles including flv(r)-like and flv(mr) alleles. although there ...199910211958
electron microscopic diagnosis of human flavivirus encephalitis: use of confocal microscopy as an aid.the distinction between intracranial viral infections and inflammatory conditions requiring immunosuppression is important. although specific laboratory reagents are readily available for some viruses, diagnosis of arbovirus infection is more difficult. transmission electron microscopy (tem) theoretically allows identification of viral particles independent of reagent availability, but it has limited sensitivity. we report two cases of human flavivirus encephalitis diagnosed by tem. laser scanni ...199910524522
identification and analysis of truncated and elongated species of the flavivirus ns1 protein.the flavivirus non-structural glycoprotein ns1 is often detected in western blots as a heterogeneous cluster of bands due to glycosylation variations, precursor-product relationships and/or alternative cleavage sites in the viral polyprotein. in this study, we determined the basis of structural heterogeneity of the ns1 protein of murray valley encephalitis virus (mve) by glycosylation analysis, pulse-chase experiments and terminal amino acid sequencing. inhibition of n-linked glycosylation by tu ...199910225275
unlicensed vaccines and bioweapon defense in world war ii. 199910478686
genetic interaction of flavivirus nonstructural proteins ns1 and ns4a as a determinant of replicase function.nonstructural protein 1 (ns1) of yellow fever virus (yf) is a glycoprotein localized to extracytoplasmic compartments within infected cells. we have previously shown that ns1 can be supplied in trans and is required for viral rna replication, a process thought to occur in membrane-bound cytoplasmic complexes. here we report that the ns1 gene from a related virus, dengue virus (den), is unable to function in the process of yf rna replication. this virus-specific incompatibility leads to a lack of ...199910233920
nascent flavivirus rna colocalized in situ with double-stranded rna in stable replication complexes.incorporation of bromouridine (bru) into viral rna in kunjin virus-infected vero cells treated with actinomycin d was monitored in situ by immunofluorescence using antibodies reactive with br-rna. the results showed unequivocally that nascent viral rna was located focally in the same subcellular site as dsrna, the putative template for flavivirus rna synthesis. when cells were labeled with bru for 15 min, the estimated cycle period for rna synthesis, the nascent br-rna was not digested in permea ...199910329573
prevalence of gbv-c/hgv-rna, virus genotypes, and anti-e2 antibodies in autoimmune hepatitis.we investigated the prevalence of hepatitis g-rna (gbv-c/hgv-rna), a recently cloned new flavivirus, and of antibodies to the envelope 2 antigen (anti-e2), a marker of past infection, in patients with autoimmune hepatitis, and compared it with the prevalence in patients with chronic viral hepatitis and healthy control individuals.199910566740
rapid serologic diagnosis of dengue virus infection using a commercial capture elisa that distinguishes primary and secondary infections.a commercial capture elisa for specific igm and igg antibodies produced during dengue infection (panbio dengue duo) showed excellent sensitivity (99%, n = 78) using sera collected at hospital discharge compared with established elisa and hemagglutination inhibition (hai) assays. furthermore, the elisa was able to diagnose 79% of the dengue cases using sera collected at hospital admission. the elisa also showed high specificity (92%) in paired sera from patients without flavivirus infection (n = ...199910348250
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