Functional and Structural Studies of Env-mediated Fusion

描述(申请人提供)：病毒进入宿主细胞是 通常被认为是感染的初始步骤，因此，确定 入侵机制对于了解病毒的生命周期至关重要。在……里面 此外，进入的特异性是病毒的主要决定因素之一 归性与病机。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，不仅是在阻止病毒附着到 宿主细胞，但也在抑制包膜介导的融合方面。另外， 了解进入已被证明是潜在的基因治疗的关键 应用程序，其中许多策略要求将重组病毒作为靶向 特定的细胞或组织。这项提议的目的是概述一个 一系列旨在阐明病毒融合机制的实验， 用禽反转录病毒劳斯肉瘤病毒(RSV)作为通用模型 病毒入侵。具体目标如下：1)信封特征化 受体诱导触发有缺陷的突变体；2)研究 PH在RSV进入中的作用：3)纯化融合装置的组件 用于结构测定。

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.