Watanabe Kazumasa, Yoshioka Kentaro, Yano Motoyoshi, Ishigami Masatoshi, Ukai Koji, Ito Hiroshi, Miyata Fumiyuki, Mizutani Tetsuya, Goto Hidemi
Department of Internal Medicine, Division of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
J Med Virol. 2005 Apr;75(4):504-12. doi: 10.1002/jmv.20301.
The nonstructural 5B (NS5B) protein of hepatitis C virus possesses RNA-dependent RNA polymerase activity and plays an essential role in viral replication. The mutations in NS5B were determined and the correlation with viral load and response to interferon (IFN) were assessed. The entire NS5B region in 33 patients and its thumb domain in 62 patients was sequenced. The number of amino acid substitutions in the NS5B protein, that in thumb domain and the substitution at aa 389 was correlated with viral load and the response to IFN. Multivariate analysis selected only mutation in IFN sensitivity determining region (ISDR) as a factor associated with the viral load and response to IFN. The number of substitutions in the thumb domain and the substitution at aa 389 correlated with the number of substitutions in the ISDR. These results suggest that mutations in NS5B, especially in the thumb domain and at aa 389, have an important effect on viral load and the response to IFN, although they were dependent on mutations in ISDR. Further studies on the relationship between NS5B and NS5A (ISDR) are necessary to elucidate the mechanism of the correlation with viral load and the response to IFN.
丙型肝炎病毒的非结构5B（NS5B）蛋白具有RNA依赖性RNA聚合酶活性，在病毒复制中起重要作用。确定了NS5B中的突变，并评估了其与病毒载量及对干扰素（IFN）反应的相关性。对33例患者的整个NS5B区域及62例患者的拇指结构域进行了测序。NS5B蛋白中的氨基酸替换数量、拇指结构域中的替换数量以及第389位氨基酸的替换与病毒载量和对IFN的反应相关。多变量分析仅选择干扰素敏感性决定区（ISDR）中的突变作为与病毒载量和对IFN反应相关的因素。拇指结构域中的替换数量和第389位氨基酸的替换与ISDR中的替换数量相关。这些结果表明，NS5B中的突变，尤其是拇指结构域和第389位氨基酸处的突变，对病毒载量和对IFN的反应有重要影响，尽管它们依赖于ISDR中的突变。有必要进一步研究NS
