Document Detail

Evolution of hepatitis C virus quasispecies during ribavirin and interferon-alpha-2b combination therapy and interferon-alpha-2b monotherapy.
MedLine Citation:
PMID:  16926548     Owner:  NLM     Status:  MEDLINE    
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. 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. 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. 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.
Keiko Arataki; Hiromitsu Kumada; Kiyomi Toyota; Waka Ohishi; Shoichi Takahashi; Susumu Tazuma; Kazuaki Chayama
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Publication Detail:
Type:  Journal Article     Date:  2006-08-21
Journal Detail:
Title:  Intervirology     Volume:  49     ISSN:  0300-5526     ISO Abbreviation:  Intervirology     Publication Date:  2006  
Date Detail:
Created Date:  2006-10-09     Completed Date:  2006-11-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0364265     Medline TA:  Intervirology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  352-61     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2006 S. Karger AG, Basel.
Department of Internal Medicine, Kure Medical Association Hospital, Kure-shi, and Department of Medicine and Molecular Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
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MeSH Terms
5' Untranslated Regions / genetics
Antiviral Agents / pharmacology,  therapeutic use
Drug Therapy, Combination
Evolution, Molecular*
Genetic Drift
Genome, Viral
Hepacivirus / classification,  drug effects,  genetics*
Hepatitis C, Chronic / drug therapy*,  virology*
Interferon Alfa-2b / pharmacology,  therapeutic use*
Ribavirin / pharmacology,  therapeutic use*
Sequence Analysis, DNA
Sequence Homology
Viral Envelope Proteins / genetics
Viral Nonstructural Proteins / genetics
Reg. No./Substance:
0/5' Untranslated Regions; 0/Antiviral Agents; 0/E1 protein, Hepatitis C virus; 0/NS-5 protein, hepatitis C virus; 0/Viral Envelope Proteins; 0/Viral Nonstructural Proteins; 157184-61-7/glycoprotein E2, Hepatitis C virus; 36791-04-5/Ribavirin; 99210-65-8/Interferon Alfa-2b

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