Functional and Structural Studies of Env-mediated Fusion

环境介导的融合的功能和结构研究

• 批准号: 6405510
• 负责人: SEAN M AMBERG
• 金额: $ 4.38万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6405510
• 关键词: Rous sarcoma virus; acid base balance; gene mutation; protein purification; protein structure function; tissue /cell culture; virus infection mechanism; virus protein; virus receptors

DESCRIPTION (provided by applicant): Viral entry into the host cell is generally considered the initial step of infection, and as such, determining the mechanism of entry is critical for understanding the virus life cycle. In addition, the specificity of entry is one of the major determinants of viral tropism and pathogenesis. Viral entry has thus provided an attractive target for antiviral therapy, not only in terms of blocking virus attachment to the host cell, but also in terms of inhibiting envelope-mediated fusion. Also, understanding entry has proven essential for potential genetic therapy applications, in which many strategies call for targeting recombinant virus to a specific cell or tissue. The objective of this proposal is to outline a series of experiments designed to elucidate the mechanism of viral fusion, using the avian retrovirus Rous sarcoma virus (RSV) as a general model for viral entry. The specific goals are the following: 1) characterize envelope mutants which are defective for receptor-induced triggering; 2) investigate the role of pH in RSV entry: and 3) purify the components of the fusion apparatus for structure determination.

描述（由申请方提供）：病毒进入宿主细胞是 通常被认为是感染的初始步骤，因此， 病毒进入的机制对于了解病毒的生命周期至关重要。在 此外，进入的特异性是病毒的主要决定因素之一， 归经和发病机理。因此，病毒进入提供了一个有吸引力的目标 对于抗病毒治疗，不仅在阻断病毒附着到 宿主细胞，而且在抑制细胞因子介导的融合方面。还有， 了解进入对于潜在的基因治疗至关重要 应用，其中许多策略要求靶向重组病毒， 一种特定的细胞或组织。本提案的目的是概述一个 一系列旨在阐明病毒融合机制的实验， 使用禽类逆转录病毒劳斯肉瘤病毒（RSV）作为一般模型， 病毒入侵具体目标如下：1）表征包络 突变体是有缺陷的受体诱导的触发; 2）研究 pH在RSV进入中的作用;和3）纯化融合器的组分 用于结构测定。