Molecular virology of hepatitis C virus.
Molecular virology of hepatitis C virus.
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丙型肝炎病毒的分子病毒学。
DOI：
10.18926/amo/32025
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发表时间：
2001
影响因子：
0.5
通讯作者：
N. Kato
中科院分区：
文献类型：
--
作者：
N. Kato
丙型肝炎病毒(丙型肝炎病毒)于1989年被发现，是世界范围内非甲非乙型肝炎的主要病原体。随着诊断丙型肝炎病毒感染的方法的发展，很明显，丙型肝炎病毒经常导致慢性肝炎。持续感染丙型肝炎病毒与肝硬变和肝细胞癌有关。目前的全球估计表明，已有超过1.7亿人感染了丙型肝炎病毒，丙型肝炎病毒是一种包膜阳性的单链RNA病毒(9.6千碱基)，属于黄病毒科。丙型肝炎病毒基因组显示出显著的序列变异，特别是在E2蛋白编码区的高变区1，在全球范围内，丙型肝炎病毒似乎分布着30多种基因类型。复杂的“准种”和频繁的病毒基因组突变也出现了。丙型肝炎病毒基因组编码一个约3,000个氨基酸残基的多蛋白前体，该前体蛋白被宿主和病毒蛋白酶切割，产生至少10个蛋白质，其顺序如下：NH2-核心-包膜(E1)-E2-p7-非结构蛋白2(NS2)-NS3-NS4A-NS4B-NS5A-NS5B-COOH。这些病毒蛋白不仅在病毒复制中发挥作用，而且还影响各种细胞功能。尽管已经提出了几种解释，但对丙型肝炎病毒在靶细胞中的感染和复制机制，持续病毒感染的机制，以及肝病(肝炎或肝细胞癌)的发病机制都知之甚少。这些机制仍不清楚的一个主要原因是缺乏一个良好的实验性丙型肝炎病毒复制系统。虽然已经报道了几种使用培养细胞进行的经典试验，但有几种新的、更有前景的实验策略(几代感染性cdna克隆、复制子、动物模型等)。目前正在进行设计和测试，以解决这些问题。此外，治疗慢性肝炎的新疗法也已开发出来。到目前为止在丙型肝炎病毒研究领域收集的大量信息总结如下，并概述了丙型肝炎病毒分子病毒学的现状。
Hepatitis C virus (HCV), discovered in 1989, is the major causative agent of parenteral non-A, non-B hepatitis worldwide. Following the development of a method of diagnosing HCV infection, it became apparent that HCV frequently causes chronic hepatitis. Persistent infection with HCV is implicated in liver cirrhosis and hepatocellular carcinoma. Current worldwide estimations suggest that more than 170 million people have been infected with HCV, an enveloped positive single-stranded RNA (9.6-kilobases) virus belonging to the Flaviviridae. The HCV genome shows remarkable sequence variation, especially in the hypervariable region 1 of the E2 protein-encoding region, and globally, HCV appears to be distributed with more than 30 genotypes. Complicated "quasispecies" and frequent mutations of viral genomes have also emerged. The HCV genome encodes a large polyprotein precursor of about 3,000 amino acid residues, and this precursor protein is cleaved by the host and viral proteinases to generate at least 10 proteins in the following order: NH2-core-envelope (E1)-E2-p7-nonstructural protein 2 (NS2)-NS3-NS4A-NS4B-NS5A-NS5B-COOH. These viral proteins not only function in viral replication but also affect a variety of cellular functions. Although several explanations have been proposed, the mechanisms of HCV infection and replication in targeted cells, the mechanism of persistent viral infection, and the pathogenesis of hepatic diseases (hepatitis or hepatocellular carcinoma) are all poorly understood. A major reason why these mechanisms remain unclear is the lack of a good experimental HCV replication system. Although several classical trials using cultured cells have been reported, several new, more promising experimental strategies (generations of infectious cDNA clone, replicon, animal models, etc.) are currently being designed and tested, in order to resolve these problems. In addition, new therapies for chronic hepatitis have also been developed. The enormous body of information collected thus far in the field of HCV research is summarized below, and an overview of the current status of HCV molecular virology of HCV is provided.