MOLECULAR BIOLOGY OF HEPATITIS C VIRUS

丙型肝炎病毒的分子生物学

• 批准号: 3746587
• 负责人: R H MILLER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3746587
• 关键词: genome; hepatitis C virus; microorganism culture; microorganism immunology; molecular biology; neutralizing antibody; nucleic acid sequence; nucleocapsid; virus RNA; virus genetics; virus replication

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.

丙型肝炎病毒（HCV）是一种重要的人类病原体，可以引起 急性和慢性肝炎，肝硬化，可能， 肝细胞癌这种病毒占社区的25%- 获得性肝炎和超过90%的输血相关性肝炎， 美国的 病毒颗粒含有正极性， 具有5'和3'非编码（NC）区的单链RNA基因组。 的 核心（C）、包膜1（E1）和包膜2（E2）蛋白质编码于 非结构蛋白在3'端编码 一个开放的阅读框架。 此外，发现 HCV基因组的遗传异质性，特别是在基因 编码包膜蛋白，表明可能存在异质性， 与人类免疫缺陷病毒包膜基因中所见的相似 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，我们扩展了我们以前的序列 分析病毒基因组，包括核心基因，这是最 HCV保守基因该基因的系统发育分析在 与高度可变的包膜1基因一致。 额外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 其他主要发现包括：（i）HCV的鉴定 透析患者中的RNA;（ii）预防黑猩猩中的HCV感染 在抗体介导的体外中和之后;和（iii） 无抗体原型菌株的建立和鉴定 HCV的不同基因型。