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Evolution of hepatitis C virus quasispecies during ribavirin and interferon-alpha-2b combination therapy and interferon-alpha-2b monotherapy.
- Source :
-
Intervirology [Intervirology] 2006; Vol. 49 (6), pp. 352-61. Date of Electronic Publication: 2006 Aug 21. - Publication Year :
- 2006
-
Abstract
- Objective: Ribavirin and interferon combination therapy is more effective than interferon monotherapy in patients with chronic hepatitis C virus (HCV) infection. To test the hypothesis that ribavirin induces nucleotide substitutions in the viral genome and reduces viral load by forcing it into error catastrophe in the combination therapy, we investigated the molecular evolution of HCV quasispecies in 3 patients who received combination therapy and 2 patients who received interferon monotherapy.<br />Methods: The quasispecies were analyzed before and after therapy by sequencing at least 8 clones in five regions of the HCV genome; 5' untranslated region, EI, E2, NS5A and NS5B.<br />Results: Marked genetic drift was observed in the NS5A and NS5B regions in patients treated with combination therapy. However, genetic distances between clones obtained after therapy were closer than those obtained before therapy.<br />Conclusion: Our results suggest that the combination therapy modified HCV quasispecies, but that this did not reflect the induction of error catastrophe by ribavirin. Modification of quasispecies by this therapy requires further investigation in a larger number of patients to elucidate the possible mechanism of viral resistance against the combination therapy.<br /> (Copyright (c) 2006 S. Karger AG, Basel.)
- Subjects :
- 5' Untranslated Regions genetics
Antiviral Agents pharmacology
Antiviral Agents therapeutic use
Drug Therapy, Combination
Genetic Drift
Genome, Viral
Hepacivirus classification
Hepacivirus drug effects
Humans
Interferon alpha-2
Interferon-alpha pharmacology
Male
Mutation
Phylogeny
Recombinant Proteins
Ribavirin pharmacology
Sequence Analysis, DNA
Sequence Homology
Viral Envelope Proteins genetics
Viral Nonstructural Proteins genetics
Evolution, Molecular
Hepacivirus genetics
Hepatitis C, Chronic drug therapy
Hepatitis C, Chronic virology
Interferon-alpha therapeutic use
Ribavirin therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0300-5526
- Volume :
- 49
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Intervirology
- Publication Type :
- Academic Journal
- Accession number :
- 16926548
- Full Text :
- https://doi.org/10.1159/000095155