MOLECULAR BIOLOGY OF HEPATITIS C VIRUS

丙型肝炎病毒是一种重要的人类病原体，可引起 急性和慢性肝炎，肝硬变，可能， 肝细胞癌。这种病毒占社区的25%- 年获得性肝炎和90%以上的输血相关性肝炎 美国。病毒颗粒含有正极性， 含有5‘和3’非编码区的单链RNA基因组。这个 核心(C)、包膜1(E1)和包膜2(E2)蛋白编码在 5‘端编码非结构蛋白，3’端编码非结构蛋白 基因组的单一开放阅读框架。此外，这一发现 丙型肝炎病毒基因组的遗传异质性，特别是在基因上 编码包膜蛋白，表明可能存在异质性 与人类免疫缺陷的包膜基因相似 病毒。这样的发现对疫苗的尝试来说是个坏兆头。 发展。在这个项目中，我们扩展了之前的序列 分析病毒基因组中包含的核心基因，这是最多的 保守的丙型肝炎病毒基因。该基因的系统发育分析已在 与高度可变的包膜1基因的同源性。 进一步的分析确定了核心基因的保守特征 将有助于理解核衣壳蛋白在 病毒复制。其他主要发现是：(I)确定丙型肝炎病毒 透析患者体内的RNA；(Ii)预防黑猩猩感染丙型肝炎病毒 在抗体介导的体外中和后；及(Iii) 猪瘟病毒无抗体原型株的建立及鉴定 丙型肝炎病毒的不同基因型别。

Hepatitis C virus (HCV) is an important human pathogen that can cause acute and chronic hepatitis, liver cirrhosis and, possibly, hepatocellular carcinoma. This virus accounts for up to 25% of community- acquired hepatitis and over 90% of transfusion-associated hepatitis in the United States. The virus particles contain a positive polarity, single-stranded RNA genome with 5' and 3' noncoding (NC) regions. The core (C), envelope 1 (E1) and envelope 2 (E2) proteins are encoded at the 5' terminus and the nonstructural proteins are encoded at the 3' terminus of the single open reading frame of the genome. Furthermore, the finding of genetic heterogeneity of the HCV genome, especially in the genes encoding the envelope proteins, suggests that there may be heterogeneity similar to that seen in the envelope gene of human immunodeficiency viruses. Such a finding would bode ill for attempts at vaccine development. In this project we have extended our previous sequence analysis of the viral genome to include the core gene, which is the most conserved HCV gene. The phylogenetic analysis of this gene was in agreement with that of the envelope 1 gene, which is highly variable. Additional analysis identified conserved features of the core gene that will be useful in understanding the role of the nucleocapsid protein in viral replication. Other major findings were: (i) identification of HCV RNA in dialysis patients; (ii) prevention of HCV infection in chimpanzees following antibody-mediated neutralization in vitro; and (iii) establishment and characterization of antibody-free prototype strains of the different genotypes of HCV.