Department of Biochemistry & Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Indian J Med Res. 2010 Jan;131:17-34.
Hepatitis C virus (HCV) is a small (approximately 55 to 65 nm), spherical, enveloped, hepatotropic RNA virus that causes acute and chronic hepatitis in humans. Persistent virus infection with HCV often leads to cirrhosis and hepatocellular carcinoma (HCC). At present there is neither a selective antiviral therapy nor a preventive vaccine. The only available treatment option is a long-acting pegylated-interferon-alpha, given in combination with nucleoside analog ribavirin, which is not very effective. Molecular studies of HCV began with the successful cloning of its genome in 1989. For many years, research to develop therapeutics was stalled by the inability to grow virus in tissue culture. A major milestone was achieved with the recent development of a robust cell culture system for HCV propagation. HCV proteins assemble and form replication complexes on modified host membranes, called as membranous webs. Even though HCV is detected and targeted by host immune mechanisms, it establishes and maintains a life-long persistent infection. HCV has evolved multiple strategies to survive and persist in hostile cellular environments; and the viral population is known to rapidly change during the course of a natural infection thereby escaping immune surveillance. Rapid mutations also help virus to survive by selecting for the variants which are resistant to antiviral drugs. Although precise mechanisms regulating HCV entry into hepatic cells via receptors remain unknown, HCV also has the capability of direct cell-to-cell transmission. The extremely complex and incompletely understood nature of the HCV lifecycle has complicated the discovery of new therapies. A complete understanding of the functional roles played by the HCV proteins during HCV lifecycle is vital for developing a successful cure. This review deals with current status of efforts in addressing these daunting tasks and challenges in developing therapeutics against chronic and rapidly changing hepatitis C virus.
丙型肝炎病毒（HCV）是一种小型（约 55 至 65nm）、球形、包膜、嗜肝 RNA 病毒，可导致人类急性和慢性肝炎。HCV 的持续性病毒感染常导致肝硬化和肝细胞癌（HCC）。目前既没有选择性抗病毒治疗，也没有预防疫苗。唯一可用的治疗选择是长效聚乙二醇干扰素-α，与核苷类似物利巴韦林联合使用，但效果并不理想。HCV 的分子研究始于 1989 年其基因组的成功克隆。多年来，由于无法在组织培养中生长病毒，研究开发治疗方法一直停滞不前。随着最近开发出用于 HCV 繁殖的强大细胞培养系统，这一重大里程碑得以实现。HCV 蛋白在称为膜网的改良宿主膜上组装并形成复制复合物。尽管 HCV 被宿主免疫机制检测和靶向，但它仍建立并维持终身持续性感染。HCV 已进化出多种策略来在恶劣的细胞环境中生存和持续存在；并且已知在自然感染过程中病毒群体迅速变化，从而逃避免疫监视。快速突变也有助于病毒通过选择对抗病毒药物具有抗性的变体来生存。尽管通过受体进入肝细胞的确切机制仍不清楚，但 HCV 也具有直接细胞间传播的能力。HCV 生命周期极其复杂且不完全了解，这使得新疗法的发现变得复杂。全面了解 HCV 蛋白在 HCV 生命周期中发挥的功能作用对于开发成功的治疗方法至关重要。本综述涉及目前在解决这些艰巨任务和挑战方面的努力，这些任务和挑战涉及针对慢性和快速变化的丙型肝炎病毒开发治疗方法。
