MOLECULAR ANALYSIS OF HEPATITIS B VIRUS

乙型肝炎病毒的分子分析

• 批准号: 3129131
• 负责人: WILLIAM J RUTTER
• 金额: $ 16.31万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-07-01 至 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3129131
• 关键词: disease carrier state; gene expression; genetic transcription; genetic translation; hepatitis B virus group; human subject; human tissue; liver cells; molecular cloning; molecular pathology; nucleic acid sequence; radiotracer; tissue /cell culture; virus antigen; virus classification; virus genetics; virus replication; yeasts

The proposed research can be divided into two main aspects. The first concerns studies on the hepatitis B virus (HBV) life cycle. The aim of this work is a comprehensive understanding of the virus and how it functions to replicate itself in the hepatic cell. It includes (1) a comprehensive analysis of HBV genes (surface (HBsAg), core (HBcAg) antigens, DNA polymerase?, and a 750b RNA) and their expression in vivo and in vitro. In addition, we will determine the nature of the "e" antigen. (2) Analysis of presumed replicative forms of the virus and the cotnrol of replication of the virus. (3) The molecular characterization of the 22nm HBsAg particle. (4) A study of the molecular basis of hepatotropism--a search for a putative HBV receptor. (5 Development of an in vitro system for studying infectivity and vegetative growth of the virus. The second major aspect concerns an analysis of the role of HBV in disease. The aim of these studies is to elucidate the molecular basis of HBV induced hepatitis and to directly test whether HBV os tje causative agent of PHC. The proposal includes (1) studies of the various viral DNA forms andof virus-derived HBsAg particles in the liver and serum of infected patients--various forms of hepatitis (self limited hepatitis, fulminant hepatitis, chronic hepatitis, carriers), and in primary hapatocellular carcinoma (HPC). (2) Analysis of structure and expression of HBV sequences integrated in genomic DNA of hapatomas and the biochemical consequences of this integration. This may reveal the molevular outline of a basic ontological process. (3) Tests whether the expression of single or pairs of virus genes will cause cellular lesions. These studies will contribute to our knowledge of viruses and viral diseases. They may illuminate the etiology of the world's most prevalent cancer. In addition they will contribute undersanding of basic molecular details of gene structure, and regulation of gene expression in mammalian cells as well as the molecular specifics of host-tissue specificity.

拟议的研究可以分为两个主要方面。 第一个 关注有关肝炎病毒（HBV）生命周期的研究。 目的 这项工作是对病毒及其如何的全面理解 在肝细胞中复制自身的功能。 它包括（1） HBV基因（表面（HBSAG），核心（HBCAG）的全面分析 抗原，DNA聚合酶？和750b RNA）及其在体内的表达 体外。 此外，我们将确定“ E”抗原的性质。 （2）分析病毒的假定复制形式和cotnrol 复制病毒。 （3）22nm的分子表征 Hbsag粒子。 （4）对肝脏主义的分子基础的研究 - a 搜索假定的HBV受体。 （5体外系统的开发 用于研究病毒的感染性和营养生长。 第二个 主要方面涉及对HBV在疾病中的作用的分析。 目的 这些研究是阐明HBV诱导的分子基础 肝炎并直接测试PHC的HBV OS TJE致病剂。 该提案包括（1）对各种病毒DNA形式和FOF的研究 肝脏中的病毒衍生的HBSAG颗粒和感染的血清 患者 - 肝炎的多种形式（自我有限的肝炎，暴发 肝炎，慢性肝炎，携带者）和原发性肝炎 癌（HPC）。 （2）分析HBV序列的结构和表达 集成在Hapatomas的基因组DNA和生化后果中 这个整合。 这可能揭示了基本的巨大轮廓 本体论过程。 （3）测试单个还是对的表达 病毒基因会引起细胞病变。 这些研究将有助于 据我们了解病毒和病毒疾病。 他们可能会照亮 世界上最普遍的癌症的病因。 另外，他们将 贡献基因结构的基本分子细节，并 调节哺乳动物细胞中基因表达以及分子 主机组织特异性的细节。