Intervirology 2006;49:352–361

Evolution of Hepatitis C Virus Quasispecies during Ribavirin and Interferon-Alpha-2b Combination Therapy and Interferon-Alpha-2b Monotherapy

Arataki K.a · Kumada H.b · Toyota K.c · Ohishi W.c · Takahashi S.c · Tazuma S.c · Chayama K.c
aDepartment of Internal Medicine, Kure Medical Association Hospital, Kure-shi, bDepartment of Gastroenterology, Toranomon Hospital, Tokyo, and cDepartment of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan
email Corresponding Author

 goto top of outline Key Words

  • Hepatitis C virus quasispecies
  • Viral resistance
  • Error catastrophe
  • Chronic hepatitis C virus infection
  • Ribavirin

 goto top of outline 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. 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.

Copyright © 2006 S. Karger AG, Basel

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 goto top of outline Author Contacts

Dr. Kazuaki Chayama
Department of Medicine and Molecular Science, Division of Frontier Medical Science
Programs for Biomedical Research, Graduate School of Biomedical Sciences
Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan)
Tel. +81 82 257 5190, Fax +81 82 255 6220, E-Mail

 goto top of outline Article Information

Received: August 25, 2005
Accepted after revision: October 26, 2005
Published online: August 21, 2006
Number of Print Pages : 10
Number of Figures : 3, Number of Tables : 2, Number of References : 33

 goto top of outline Publication Details

Intervirology (International Journal of Basic and Medical Virology)

Vol. 49, No. 6, Year 2006 (Cover Date: October 2006)

Journal Editor: Liebert, U.G. (Leipzig)
ISSN: 0300–5526 (print), 1423–0100 (Online)

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