Perspectives for the treatment of infections with Flaviviridae.
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The family Flaviviridae contains three genera: Hepacivirus, Flavivirus, and Pestivirus. Worldwide, more than 170 million people are chronically infected with Hepatitis C virus and are at risk of developing cirrhosis and/or liver cancer. In addition, infections with arthropod-borne flaviviruses (such as dengue fever, Japanese encephalitis, tick-borne encephalitis, St. Louis encephalitis, Murray Valley encephalitis, West Nile, and yellow fever viruses) are emerging throughout the world. The pestiviruses have a serious impact on livestock. Unfortunately, no specific antiviral therapy is available for the treatment or the prevention of infections with members of the Flaviviridae. Ongoing research has identified possible targets for inhibition, including binding of the virus to the cell, uptake of the virus into the cell, the internal ribosome entry site of hepaciviruses and pestiviruses, the capping mechanism of flaviviruses, the viral proteases, the viral RNA-dependent RNA polymerase, and the viral helicase. In light of recent developments, the prevalence of infections caused by these viruses, the disease spectrum, and the impact of infections, different strategies that could be pursued to specifically inhibit viral targets and animal models that are available to study the pathogenesis and antiviral strategies are reviewed. (+info)
Standardization of immunoglobulin M capture enzyme-linked immunosorbent assays for routine diagnosis of arboviral infections.
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Immunoglobulin M antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) is a rapid and versatile diagnostic method that readily permits the combination of multiple assays. Test consolidation is especially important for arthropod-borne viruses (arboviruses) which belong to at least three virus families: the Togaviridae, Flaviviridae, and Bunyaviridae. Using prototype viruses from each of these families and a panel of well-characterized human sera, we have evaluated and standardized a combined MAC-ELISA capable of identifying virus infections caused by members of each virus family. Furthermore, by grouping antigens geographically and utilizing known serological cross-reactivities, we have reduced the number of antigens necessary for testing, while maintaining adequate detection sensitivity. We have determined that a 1:400 serum dilution is most appropriate for screening antiviral antibody, using a positive-to-negative ratio of >/=2.0 as a positive cutoff value. With a blind-coded human serum panel, this combined MAC-ELISA was shown to have test sensitivity and specificity that correlated well with those of other serological techniques. (+info)
Prevalence of and risk factors for hepatitis G (HGV) infection in haemodialysis patients: a multicentre study.
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BACKGROUND: Hepatitis G virus (HGV) or GB-virus type C (GBV-C) is, like hepatitis C, a blood-borne virus and a member of the family of flaviviridae. HGV is distributed globally and is present in the volunteer blood donor population. Thus, for epidemiological reasons, HGV is of interest in haemodialysis patients, who are at risk of parenterally transmitted infections. The aim of the present investigation was to assess the prevalence of HGV by antibody testing and HGV-RNA determination by PCR. METHODS: The study was performed in haemodialysis units of the Patienten-Heim-Versorgung, an organization of haemodialysis units throughout Germany. A total of 2796 out of 3042 patients (92%) from 43 haemodialysis units were enrolled prospectively in the trial. Liver function tests were performed and epidemiologic data were obtained to evaluate risk factors for HGV in haemodialysis patients. RESULTS: Antibodies against HGV were detected in 485 patients (17.5%). Viraemia was seen in 380 out of 1935 patients tested (19.6%). Fifty-eight patients (3.0%) were positive for both antibodies and HGV-RNA. Using a standard questionnaire in 1717 out of the 2786 patients, it was found that more than five blood transfusions increased the risk of HGV infection significantly (P<0.05). There was no association found between HGV infection and the length of time on haemodialysis. CONCLUSION: HGV is common in German haemodialysis patients but, in contrast to other parenterally transmitted viruses, there is no further risk for new infections during haemodialysis, except for patients who have received several blood transfusions. (+info)
A study on pathogenicity of hepatitis G virus.
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AIM: To study the pathogenicity of hepatitis G virus (HGV) and observe the genesis and pathological process of hepatitis G. METHODS: HGV-RNA in serum was detected by RT-PCR assay. The immunohistochemical assays of liver tissue were performed with HGV monocoloned antibody (McAb) expressed from the region of HGV NS5 nucleic acid sequence. The clinical and pathological data of 52 patients with hepatitis G were discussed. In animal experiment, the Chinese Rhesus monkeys were infected with the serum of a patient with HGV infection. And the dynamic changes in serology and liver histology of animals were observed. RESULTS: One hundred and fifty-four patients with HGV-RNA positive were selected from 1552 patients with various kinds of hepatitis. Of 154 patients with HGV infection, 52 were infected with HGV only, which accounted for 33.8 (52/154) and 102 with positive HGV-RNA were super-infected with other hepatitis viruses, which accounted for 66.2 (102/154). The clinical and pathological observation showed that the acute and chronic hepatitis could be induced by HGV. The slight abnormality of transaminases ALT and AST in serum of monkeys lasted nearly 12 months and histological results showed a series of pathological changes. CONCLUSION: HGV is a hepatotropic virus and has pathogenicty. (+info)
Lack of both Fas ligand and perforin protects from flavivirus-mediated encephalitis in mice.
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The mechanism by which encephalitic flaviviruses enter the brain to inflict a life-threatening encephalomyelitis in a small percentage of infected individuals is obscure. We investigated this issue in a mouse model for flavivirus encephalitis in which the virus was administered to 6-week-old animals by the intravenous route, analogous to the portal of entry in natural infections, using a virus dose in the range experienced following the bite of an infectious mosquito. In this model, infection with 0.1 to 10(5) PFU of virus gave mortality in approximately 50% of animals despite low or undetectable virus growth in extraneural tissues. We show that the cytolytic effector functions play a crucial role in invasion of the encephalitic flavivirus into the brain. Mice deficient in either the granule exocytosis- or Fas-mediated pathway of cytotoxicity showed delayed and reduced mortality. Mice deficient in both cytotoxic effector functions were resistant to a low-dose peripheral infection with the neurotropic virus. (+info)
Evidence for probable sexual transmission of the hepatitis g virus.
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A cross-sectional epidemiology study evaluated the role of sexual activity and sexually transmitted diseases (STDs) in the transmission of hepatitis G virus (HGV/GBV-C) and other hepatitis virus infections in 944 subjects. There was a statistically significant higher prevalence of HGV/GBV-C, hepatitis B virus, and hepatitis C virus exposure in the STD clinic group (i.e., subjects who were currently seeking treatment for an STD) compared with the group who never had received treatment for an STD. In a comparison of the subjects with an STD versus those without an STD, the prevalence of HGV/GBV-C was 11.3% versus 4.9%, on the basis of polymerase chain reaction (PCR) results alone, and 36.6% versus 8.8%, when results of PCR and enzyme-linked immunosorbent assay were combined. Sexual activity and, possibly, the presence of an STD increases the risk of HGB/GBV-C transmission. (+info)
Liver histology in co-infection of hepatitis C virus (HCV) and hepatitis G virus (HGV).
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As little is known about liver histology in the co-infection of hepatitis C virus (HCV) and hepatitis G virus (HGV), HGV RNA was investigated in 46 blood donors with hepatitis C, 22 of them with liver biopsy: co-infection HCV / HGV (n = 6) and HCV isolated infection (n = 16). Besides staging and grading of inflammation at portal, peri-portal and lobular areas (Brazilian Consensus), the fibrosis progression index was also calculated. All patients had no symptoms or signs of liver disease and prevalence of HGV / HCV co-infection was 15.2%. Most patients had mild liver disease and fibrosis progression index, calculated only in patients with known duration of infection, was 0.110 for co-infection and 0.130 for isolated HCV infection, characterizing these patients as "slow fibrosers". No statistical differences could be found between the groups, although a lesser degree of inflammation was always present in co-infection. In conclusion co-infection HCV / HGV does not induce a more aggressive liver disease, supporting the hypothesis that HGV is not pathogenic. (+info)
High prevalence of hepatitis G virus infection in Hodgkin's disease and B-cell lymphoproliferative disorders: absence of correlation with hepatitis C virus infection.
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BACKGROUND AND OBJECTIVES: During the last decade an epidemiological association between hepatitis C virus (HCV) and B-cell lymphoproliferative disorders (B-LPD) has been reported; the same association has not been observed for Hodgkin's disease (HD). Hepatitis G virus (HGV) shares genetic and biological features with HCV, thus it might also be involved in lymphomagenesis. DESIGN AND METHODS: The aim of this study was to compare the prevalence of HCV and HGV infection in patients at diagnosis of B-LPD or HD. RESULTS: We tested 227 consecutive untransfused patients (127 with B-LPD and 100 with HD) and 110 healthy controls. The prevalence of HCV infection was significantly higher in B-LPD patients than in controls (17.3% vs. 1.8%, p<0.002 ), whereas it was the same in HD patients as in controls. In contrast, the prevalence of HGV was significantly higher in patients, both those with B-LPD (7.8% vs. 0.9%, p<0.03) and those with HD (13% vs. 0.9%, p<0.002), than in controls. Among the various B-LPD tested, HGV infection was more frequent in B-NHL (11.5%). INTERPRETATION AND CONCLUSIONS: Our data support the hypothesis that HGV infection may play a role in lymphomagenesis and that this role is different and separate from that of HCV. (+info)