Evolution of hepatitis C virus quasispecies during ribavirin and interferon-alpha-2b combination therapy and interferon-alpha-2b monotherapy

被引:14
作者
Arataki, Keiko
Kumada, Hiromitsu
Toyota, Kiyomi
Ohishi, Waka
Takahashi, Shoichi
Tazuma, Susumu
Chayama, Kazuaki
机构
[1] Hiroshima Univ, Dept Med & Mol Sci, Div Frontier Med Sci, Program Biomed Res,Grad Sch Biomed Sci,Minami Ku, Hiroshima 7348551, Japan
[2] Toranomon Gen Hosp, Dept Gastroenterol, Tokyo, Japan
[3] Kure Med Assoc Hosp, Dept Internal Med, Tokyo, Japan
关键词
hepatitis C virus quasispecies; viral resistance; error catastrophe; chronic hepatitis C virus infection; ribavirin;
D O I
10.1159/000095155
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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, El, 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 (c) 2006 S. Karger AG, Basel.
引用
收藏
页码:352 / 361
页数:10
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