丙型肝炎病毒基因组结构及功能

Hepatitis C Virus Genomic Structure and Function

丙型肝炎病毒(hepatitis C virus,HCV)是单股正链的RNA病毒,全长为9.6kb,包括1个大的开放阅读框(ORF)和两侧的5′,3′非编码区(UTRs).核糖体通过进入HCV5′UTR端的内部核糖体进入位点(IRES),将HCV基因组翻译成1个聚蛋白前体.前体聚蛋白被宿主和病毒的蛋白酶共同切割成为若干个具有独立功能的HCV蛋白,根据功能的不同分别命名为C、E1、E2、p7、NS2、NS3、NS4A、NS4B、NS5A和NS5B,它们不但在HCV的生活史中发挥着重要的作用,也影响着宿主细胞的信号传导、凋亡及物质代谢等一系列生化过程.近年来,随着HCV体外细胞摸型的不断发展,其病毒分子生物学方面的研究取得了很大的进展.本文从基因组结构及其编码的蛋白功能等方面阐述了HCV病毒的研究进展,为致病机理的研究及抗HCV药物的开发和疫苗研制等提供理论基础.

Hepatitis C virus （HCV） is a positive, single-stranded RNA virus in the Flaviviridae family. The genomic DNA is approximately 9.6-kb in length and comprises a long open reading frame （ORF） flanked by 5＇ and 3＇ untranslated regions （ UTRs）. Translation of the hepatitis C virus （HCV） RNA is mediated by binding ribosomes to an internal ribosome entry site （IRES） located within the 5＇-untranslated region （5＇-UTR）. The polyprotein is cleaved by the host and viral proteinases to generate at least 10 proteins in the following order C, envelope （El）, E2, p7, nonstructural protein 2 （NS2）, NS3, NS4A, NS4B, NS5A and NS5B. These viral proteins not only play important roles in viral replication but also affect a variety of cellular functions, such as signal transduction, cell apoptosis and material metabolism. Fascinating progress in the understanding of the molecular biology of HCV was made recently with the establishment of the replicon system. In this review, we summarized the recent advances in structure of HCV genome and its function of coding proteins and discussed future research directions. It will supply important theoretical foundation for researching immunity and diagnosis.