REPLICATION AND CAPSID ANTIGENS OF HEPATITIS A VIRUS

甲型肝炎病毒（HAV）是一种人类病原体， 这是一个全球性的健康问题，特别是在发展中国家。 病毒 是小核糖核酸病毒家族的一个非典型成员， 一个独特的属。 虽然它有着相同的一般结构和基因组 与其他picornavirsues组织，它只有有限的核苷酸或 与任何其它小核糖核酸病毒成员的氨基酸序列同源性 组 此外，HAV生长和复制的多个方面在 培养的细胞明显不同于其它小核糖核酸病毒的细胞。 尽管其他小核糖核酸病毒经历快速的裂解生长周期，但HAV 缓慢且异步地复制， 感染. 我们以前已经开始研究，以确定和表征 HAV的分子生物学，以了解其生长表型。 在 此外，我们已经在重组系统中生产了HAV蛋白，以评估 这种感染的亚单位型疫苗的可行性。 在这 应用，我们建议确定HAV帽ID的结构 蛋白质及其前体，并分析特定HAV的作用， 基因产物和序列作为病毒生长决定因素。 衣壳蛋白 加工和修饰将由生物化学和 遗传方法。 将分析5'非编码区在以下中的作用： 翻译效率和宿主范围的限制，以及病毒 调节病毒RNA的蛋白质、RNA序列和生物化学活性 将对合成进行评价。

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.