REOVIRUS OUTER-CAPSID ASSEMBLY & FUNCTIONS IN CELL ENTRY

描述：(改编自调查人员摘要)：理解 非包膜病毒穿透膜双层的机制 进入细胞可能为新的抗病毒策略提供靶点，并可能 也有助于设计更安全、更有效的疫苗、基因传递 和/或从这些病毒衍生的抗肿瘤药物。哺乳动物正病毒 是独特的模型系统，用于理解机制和调节 无包膜病毒的膜穿透。目前的提案是以 病毒粒子相关外膜的结构和细胞进入功能 衣壳蛋白Mu-1、Sigma-3和Sigma-1。该提案的具体目的 是：(1)确定外壳组装的步骤；(2)确定外壳组装的 外壳拆卸中的步骤，因为它们与单元格输入有关，并确定 MU-1蛋白如何影响病毒穿透细胞膜，(3) 确定外衣壳蛋白的结构特征与其 在条目中的组装和功能。拟议的研究之所以成为可能，是因为 在亚病毒粒子的外层重新包覆方面取得了进展 蛋白质在体外，从而恢复粒子的感染性。这些是体外培养的 重涂方法已被改造成一种新的分子遗传学 利用突变形式分析呼肠孤病毒外壳结构和功能 用于重覆的重组蛋白。

DESCRIPTION: (Adapted from the Investigator's abstract): Understanding of the mechanisms by which nonenveloped viruses penetrate membrane bilayers during entry into cells may provide targets for novel antiviral strategies, and may also be useful for designing safer and more effective vaccine, gene-delivery and/or anti-tumor agents derived from these viruses. Mammalian orthoreoviruses are unique model systems for understanding mechanisms and regulation of membrane penetration by nonenveloped viruses. The current proposal is centered on the structures and cell-entry functions of the virion-associated outer capsid proteins mu-1, sigma-3 and sigma-1. The specific aims of the proposal are to: (1) determine the steps in outer-capsid assembly, (2) determine the steps in outer-capsid disassembly as they relate to cell entry, and determine how the mu-1 protein effects virus penetration through the cell membrane, (3) identify structural features of the outer capsid proteins as relates to their assembly and functions in entry. The proposed studies are made possible because progress has been made in re-coating subvirion particles with outer coat proteins in vitro, thereby recovering particle infectivity. These in vitro recoating methods have been adapted into a new style of molecular genetic analysis of reovirus outer-capsid structure and function by using mutant forms of recombinant proteins for recoating.