丙型肝炎病毒依赖于RNA的RNA聚合酶(RdRp)研究进展

由于缺乏合适的HCV感染细胞模型，严重制约了HCV复制，特别是HCV复制的关键因子依赖于RNA的RNA聚合酶(RdRp)的研究.对HCV序列比较分析并通过异源表达证明NS5B是HCV复制的RdRp.NS5B C端疏水性氨基酸区域以及NS5B与细胞膜形成复合体等影响NS5B溶解性.在合适的反应条件下NS5B可以多种RNA分子为模板催化RNA复制，特别是能有效复制HCV全长(+)RNA.高浓度GTP激活HCV RdRp活性.NS5B N/C端缺失突变和保守性A、B、C区中的点突变影响RdRp活性，但D区345位精氨酸突变为赖氨酸时RdRp活性明显升高.HCV RdRp的发现及其功能研究为HCV药物研究提供了新型靶标.

The Advance on Research of RNA-dependent RNA Polymerase(RdRp) of Hepatitis C Virus

Due to the lack of efficient cell culture systems, animal models, the low amounts of viral antigens and RNA in infected tissues, knowledge about the replication mechanisms,especially the RNA-dependent RNA polymerase(RdRp) of hepatitis C virus(HCV) is poor.Based on analysis of amino acid sequence of HCV polyprotein and analogy to the closely related flaviviruses and pestviruses,it is assumed that NS5B may be the RdRp of HCV.By Baculovirus and E.coli expression system and in vitro RNA replication system,it was demonstrated that the de novo synthesis of RNA could be catalyzed by NS5B,which resembles other viral RdRp.The biochemical properties and the mutation-function relationships of RdRp of HCV were comprehensively reviewed,and the potential of NS5B as an important new target for antiviral therapy was also discussed.