Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Curr Top Microbiol Immunol. 2013;369:113-42. doi: 10.1007/978-3-642-27340-7_5.
Great progress has been made over the past years in elucidating the structure and function of the hepatitis C virus (HCV) proteins, most of which are now actively being pursued as antiviral targets. The structural proteins, which form the viral particle, include the core protein and the envelope glycoproteins E1 and E2. The nonstructural proteins include the p7 viroporin, the NS2 protease, the NS3-4A complex harboring protease and NTPase/RNA helicase activities, the NS4B and NS5A proteins, and the NS5B RNA-dependent RNA polymerase. NS4B is a master organizer of replication complex formation while NS5A is a zinc-containing phosphoprotein involved in the regulation of HCV RNA replication versus particle production. Core to NS2 make up the assembly module while NS3 to NS5B represent the replication module (replicase). However, HCV proteins exert multiple functions during the viral life cycle, and these may be governed by different structural conformations and/or interactions with viral and/or cellular partners. Remarkably, each viral protein is anchored to intracellular membranes via specific determinants that are essential to protein function in the cell. This review summarizes current knowledge of the structure and function of the HCV proteins and highlights recent advances in the field.
在过去的几年中，在阐明丙型肝炎病毒 (HCV) 蛋白的结构和功能方面取得了巨大进展，其中大多数现在都被积极作为抗病毒靶点进行研究。结构蛋白形成病毒颗粒，包括核心蛋白和包膜糖蛋白 E1 和 E2。非结构蛋白包括 p7 病毒孔蛋白、NS2 蛋白酶、含有蛋白酶和 NTPase/RNA 解旋酶活性的 NS3-4A 复合物、NS4B 和 NS5A 蛋白以及 NS5B RNA 依赖性 RNA 聚合酶。NS4B 是复制复合物形成的主要组织者，而 NS5A 是一种含锌的磷蛋白，参与 HCV RNA 复制与粒子生成的调节。NS2 到 NS5B 构成复制模块（复制酶），而 NS3 到 NS5B 则构成复制模块。然而，HCV 蛋白在病毒生命周期中发挥多种功能，这些功能可能受到不同结构构象和/或与病毒和/或细胞伴侣相互作用的影响。值得注意的是，每个病毒蛋白都通过特定决定因素锚定在细胞内膜上，这些决定因素对于蛋白质在细胞中的功能至关重要。本综述总结了 HCV 蛋白的结构和功能的最新知识，并强调了该领域的最新进展。
