REPLICATION AND CAPSID ANTIGENS OF HEPATITIS A VIRUS

甲型肝炎病毒(HAV)是一种人类病原体，它继续构成 世界范围内的健康问题，特别是在发展中国家。病毒 是小核糖核酸病毒家族的非典型成员，似乎代表着 一个独特的属。尽管它拥有相同的一般结构和基因组 与其他小核糖核酸病毒的组织，它只有有限的核苷酸或 与任何其他小核糖核酸病毒成员的氨基酸序列同源性 组。此外，甲型肝炎病毒的增长和复制的许多方面 培养的细胞与其他小核糖核酸病毒明显不同。 而其他小核糖核酸病毒经历快速、裂解的生长周期，甲型肝炎病毒 缓慢而异步地复制并建立持久的 感染。 我们之前已经启动了一些研究，以确定和表征 甲型肝炎病毒的分子生物学，以了解其生长表型。在……里面 此外，我们还在重组系统中生产了甲型肝炎病毒蛋白以进行评估 这种感染的亚单位类型疫苗的可行性。在这 应用，我们建议确定甲型肝炎病毒冠状病毒ID的结构 蛋白质及其前体，并分析特定甲型肝炎病毒的作用 作为病毒生长决定因素的基因产品和序列。衣壳蛋白 加工和修饰将由生物化学和 遗传方法。5‘非编码区将被分析其在 翻译效率和寄主范围限制，以及病毒 调节病毒RNA的蛋白质、RNA序列和生化活性 将对合成进行评估。

Hepatitis A virus (HAV) is a human pathogen that continues to pose a worldwide health problem, especially in developing countries. The virus is an atypical member of the picornavirus family, and appears to represent a unique genus. Although it shares the same general structure and genome organization with other picornavirsuses, it has only limited nucleotide or amino acid sequence homology to members of any of the other picornavirus groups. In addition, numerous aspects of HAV growth and replication in cultured cells differ markedly from those of other picornaviruses. Whereas other picornaviruses undergo rapid, lytic growth cycles, HAV replicates slowly and asynchronously and establishes persistent infections. We have previously initiated studies to identify and characterize the molecular biology of HAV in order to understand its growth phenotype. In addition, we have produced HAV proteins in recombinant systems to evaluate the feasibility of a subunit type vaccine for this infection. In this application, we propose to determine the structures of the HAV caps id proteins and their precursors, and to analyze the roles of specific HAV gene products and sequences as viral growth determinants. Capsid protein processing and modification will be defined by both biochemical and genetic methods. The 5' noncoding region will be analyzed for its role in translational efficiency and host range restriction, and the viral proteins, RNA sequences and biochemical activities that regulate viral RNA synthesis will be evaluated.