REOVIRUS OUTER-CAPSID ASSEMBLY & FUNCTIONS IN CELL ENTRY

描述：（改编自研究者摘要）：了解 无包膜病毒穿透膜双层的机制， 进入细胞可以为新的抗病毒策略提供靶点，并且可以 也可用于设计更安全和更有效的疫苗， 和/或衍生自这些病毒的抗肿瘤剂。哺乳动物正呼肠孤病毒 是理解生物学的机制和调控的独特模型系统， 无包膜病毒的膜渗透。目前的提案集中在 病毒体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。提案的具体目标 是：（1）确定外衣壳组装的步骤，（2）确定 外衣壳解体的步骤，因为它们涉及细胞进入，并确定 mu-1蛋白如何影响病毒穿透细胞膜，（3） 鉴定与其结构相关的外壳蛋白的结构特征， 入口处的组件和功能。这些研究之所以能够进行，是因为 在用外壳重新包被亚病毒粒子方面已经取得了进展 蛋白质，从而恢复颗粒感染性。这些体外 重包被方法已经被应用于一种新的分子遗传学方法， 用突变体分析呼肠孤病毒外壳结构和功能 重组蛋白质进行重涂。

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.