Identification of hepatitis C virus genotype 2a replicon variants with reduced susceptibility to ribavirin

被引：7

作者：

Hmwe, Su Su ^{[1
,2
]}

Aizaki, Hideki ^{[1
]}

Date, Tomoko ^{[1
]}

Murakami, Kyoko ^{[1
]}

Ishii, Koji ^{[1
]}

Miyamura, Tatsuo ^{[1
]}

Koike, Kazuhiko ^{[2
]}

Wakita, Takaji ^{[1
]}

Suzuki, Tetsuro ^{[1
]}

机构：

[1] Natl Inst Infect Dis, Dept Virol 2, Shinjuku Ku, Tokyo 1628640, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Gastroenterol, Bunkyo Ku, Tokyo 1138655, Japan

来源：

ANTIVIRAL RESEARCH | 2010年 / 85卷 / 03期

基金：

日本学术振兴会;

关键词：

Hepatitis C virus; Replication; Ribavirin; Drug resistance; SUBGENOMIC REPLICON; INTERFERON; REPLICATION; COMBINATION; POLYMERASE; RESISTANCE;

D O I：

10.1016/j.antiviral.2009.12.008

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Ribavirin (RBV), a nucleoside analogue, is used in the treatment of hepatitis C virus (HCV) infection in combination with interferons. However, potential mechanisms of RBV resistance during HCV replication remain poorly understood. Serial passage of cells harboring HCV genotype 2a replicon in the presence of RBV resulted in the reduced susceptibility of the replicon to RBV. Transfection of fresh cells with RNA from RBV-resistant replicon cells demonstrated that the RBV resistance observed is largely replicon-derived. Four major amino acid substitutions: T1134S in NS3, P1969S in NS4B, V2405A in NS5A, and Y2471H in NS5B region, were identified. Site-directed mutagenesis of these mutations into the replicon indicated that Y2471 H plays a role in the reduced susceptibility to RBV and leads to decrease in replication fitness. The results, in addition to analysis of sequence database, suggest that HCV variants with reduced susceptibility to RBV identified are preferential to genotype 2a. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：520 / 524

页数：5

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