Hepatitis C virus (HCV) exists in vivo as a highly variable mixture of closely related genomes (quasispecies), but the pathogenetic significance of such heterogeneity is still largely unknown. To investigate this issue, we compared the composition of HCV quasispecies found in the liver, peripheral blood mononuclear cells (PBMC) and plasma of ten patients by single-strand conformation polymorphism analysis of the E2/NS1 region and sequencing of the variants detected. We found considerable quasispecies differences between the liver and PBMC in all the patients, involving variant numbers, relative quantities and relative electrophoretic mobilities, but no apparent tissue-specific trend. Genome variants present in the liver and/or PBMC were not detected in the corresponding plasma samples, while certain HCV variants were present only in plasma. No dominant amino acids or amino acid pattern characteristic of variants present solely in the PBMC were detected in the E2/NS1 region sequenced.Hepatitis C virus (HCV) exists within infected hosts as a variably complex system of related genomes (quasispecies) generated by the limited fidelity of RNA replication. Recent evidence has shown that quasispecies composition exhibits extensive variation within individual isolates (Okada et al., 1992) and can vary spontaneously both over time (Kao et al., 1995) and with liver disease progression . In addition, the extent of HCV quasispecies diversity has been reported to be predictive of responsiveness to interferon treatment (Moribe et al., 1995) and to decrease markedly

Hepatitis C virus (HCV) is a leading cause of liver damage and has also been implicated in extrahepatic pathologies. We examined for HCV RNA paired CSF and plasma samples from 12 viremia positive patients using PCR. The CSF from 5/5 HIV-infected patients and 5/7 HIV-negative patients were HCV RNA positive. Branched DNA analysis showed that HCV loads in CSF were much lower than in plasma. Several HCV-positive CSF showed no evidence of blood contamination, impaired blood-brain barrier, or intrathecal IgG production. Comparison of HCV quasispecies in three sets of samples suggested that the virus in CSF was of plasma origin

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In infected individuals, hepatitis C virus (HCV) exists as a variably complex population of related genetic variants known as quasispecies. The quasispecies of HCV were studied previously in 10 chronically infected patients by single-strand conformation polymorphism analysis of a segment of the envelope gene E2/NS1 containing the hypervariable region 1 and it was found that certain variants (LC variants) were present both in the liver and in peripheral blood mononuclear cells (PBMC), others (L variants) were present in the liver but not in the PBMC, and still others (C variants) showed the opposite distribution. The sequence data obtained from nine such patients are reported, indicating that, within individual subjects, L and C variants are distinct phylogenetically. Results are described on the growth of HCV in stimulated healthy donor PBMC cultures supporting the concept that genetic divergence might stem, at least in part, from virus adaptation to growth in different cell types. This information may help to understand how HCV persists and produces disease in infected patients, especially with regard to extrahepatic pathology.

In infected individuals, hepatitis C virus (HCV) exists as a variably complex population of related genetic variants known as quasispecies. The quasispecies of HCV were studied previously in 10 chronically infected patients by single-strand conformation polymorphism analysis of a segment of the envelope gene E2/NS1 containing the hypervariable region 1 and it was found that certain variants (LC variants) were present both in the liver and in peripheral blood mononuclear cells (PBMC), others (L variants) were present in the liver but not in the PBMC, and still others (C variants) showed the opposite distribution. The sequence data obtained from nine such patients are reported, indicating that, within individual subjects, L and C variants are distinct phylogenetically. Results are described on the growth of HCV in stimulated healthy donor PBMC cultures supporting the concept that genetic divergence might stem, at least in part, from virus adaptation to growth in different cell types. This information may help to understand how HCV persists and produces disease in infected patients, especially with regard to extrahepatic pathology.