REOVIRUS OUTER-CAPSID ASSEMBLY & FUNCTIONS IN CELL ENTRY

呼肠孤病毒外衣壳组件

• 批准号: 6266761
• 负责人: MAX L. NIBERT
• 金额: $ 30.1万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6266761
• 关键词: Reoviridae; X ray crystallography; capsid; human subject; recombinant proteins; virus assembly; virus infection mechanism; virus protein

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.

描述：（改编自研究者的摘要）：对 无包膜病毒穿透双层膜的机制 进入细胞可能为新型抗病毒策略提供靶标，并且可能 也可用于设计更安全、更有效的疫苗、基因传递 和/或源自这些病毒的抗肿瘤剂。哺乳动物正呼肠孤病毒 是用于理解机制和调节的独特模型系统 无包膜病毒的膜穿透。目前的提案集中在 关于病毒粒子相关外层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 的目的是：（1）确定外衣壳组装的步骤，（2）确定 与细胞进入相关的外衣壳拆卸步骤，并确定 mu-1 蛋白如何影响病毒穿透细胞膜，(3) 识别与其相关的外衣壳蛋白的结构特征 组件和入口函数。拟议的研究之所以成为可能，是因为 在用外层重新涂覆亚病毒粒子方面取得了进展 体外蛋白质，从而恢复颗粒感染性。这些在体外 重涂方法已适应新型分子遗传学 使用突变体形式分析呼肠孤病毒外衣壳结构和功能 用于重涂的重组蛋白。