REOVIRUS OUTER-CAPSID ASSEMBLY & FUNCTIONS IN CELL ENTRY

呼肠孤病毒外衣壳组件

• 批准号: 6698773
• 负责人: MAX L. NIBERT
• 金额: $ 5.11万
• 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/6698773
• 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：（根据调查人员的摘要进行了改编）：理解 非发育病毒在此期间穿透膜双层的机制 进入细胞可能会为新型抗病毒策略提供目标，并且可以 也可用于设计更安全，更有效的疫苗，基因分娩 和/或源自这些病毒的抗肿瘤剂。哺乳动物矫形病毒 是理解机制和调节的独特模型系统 非发育病毒的膜穿透。当前的提议以中心为中心 在与病毒体相关的外部的结构和细胞进入功能上 衣壳蛋白MU-1，Sigma-3和Sigma-1。提案的具体目的 为：（1）确定外部capsid组件的步骤，（2）确定 与细胞输入相关的外部capsid拆卸中的步骤，并确定 MU-1蛋白如何影响病毒穿过细胞膜，（3） 识别外皮蛋白的结构特征与其 组件和功能在入口中。提出的研究成为可能，因为 在用外层重新涂层粒子的情况下取得了进展 体外蛋白质，从而恢复颗粒感染。这些在体外 重新陶瓷方法已改编成一种新的分子遗传样式 通过使用突变体形式分析葡萄病毒外壳结构和功能 重组蛋白用于重建。