MOLECULAR ANALYSIS OF HEPATITIS B VIRUS

这项拟议的研究旨在阐明生活中未解决的特征 乙肝病毒的周期包括各种基因表达的调节 和乙肝病毒颗粒的形成，并进一步调查 乙肝病毒相关的肿瘤发生。需要解决的具体问题包括1) 两种表面抗原的作用及其可能的独立调节 启动子，分析大分子表面抗原的功能 产物，P45，核心启动子的表征，特别是 与前核心区和核心区转录本的形成的关系，以及 聚合酶基因的可能形成。我们还将调查 核心启动子与邻近的polIII启动子的相互作用 引导从短链形成RNA。2)进一步 乙肝病毒增强子的特性包括精细定位和突变 分析、测定其激活的各种乙肝病毒启动子和 反式作用(肝脏特异性)因子的阐明 增强剂活性。3)阐明核心结构的功能 包括a)前核在e抗原形成中的作用， 包括e抗原结构的测定；b) 形成SAG/CAG复合结构的前核。4)企业的角色 整合的乙肝病毒序列在肝细胞癌发生中的作用这些研究涉及 大约20例分离的特异性肝炎和肿瘤特异性的特征 基因。

The proposed research aims to elucidate unresolved features in the life cycle of HBV including the regulation of expression of the various genes and the formation of the HBV viral particles, and to further investigate HBV-associated oncogenesis. The specific issues to be addressed include 1) the role and possible independent regulation of the two surface antigen promoters, an analysis of the function of the large surface antigen product, P45, characterization of the core promoter specifically in relation to the formation of the precore and core transcripts, and the possible formation of the polymerase gene. We will also investigate the interaction of the core promoter with a contiguous pol III promoter directing the formation of an RNA from the short strand. 2) Further characterization of the HBV enhancer including fine mapping and mutational analysis, determination of its activation of the various HBV promoters and elucidation of trans-acting (liver-specific) factor responsible for enhancer activity. 3) Elucidation of the function of core structures including a) the role of precore in the formation of the e antigen, including the determination of e antigen structures; b) the role of the precore in the formation of sAg/cAg compositive structures. 4) The role of integrated HBV sequences in HCC oncogenesis. These studies involve characterization of about 20 isolated hepatitis-specific and tumor-specific genes.