STRUCTURAL INVESTIGATION OF THE HANTAAN VIRUS L PROTEIN

描述(改编自申请人的摘要)：本雅氏病毒代表 负链RNA病毒的最大家族。每一个都包含一个基因组 由包裹在核蛋白复合体中的三个RNA片段组成。多数 布尼亚病毒在昆虫媒介中传播，但有一个明显的例外 在啮齿动物体内携带的汉坦病毒。汉滩病毒，最初的 汉坦病毒首次被证明是韩国出血性疾病的病原体 发烧，东方的一种地方病。与汉滩关系密切的病毒 然而，病毒在全球范围内分布，并与 出血热。随着最近意外爆发的急性肺炎 西南部的综合症，也是由一种被称为Sin的汉坦病毒引起的 诺布雷病毒(SNV)，在其他地区发现额外病例 以及几个新种的特征。 在北美，获取详细的汉坦病毒是很重要的 了解汉坦病毒的生命周期。中国的长期目标是 应用于阐明汉坦病毒信使核糖核酸的合成和机制 RNA复制。在这份提案中，申请者将专注于开发一种 病毒L蛋白的拓扑图。由于预期中的困难 在获得大量足以用于结构分析的纯L蛋白中 研究中，我们提出了一种新的方法来生成、识别和 L蛋白活性亚区的鉴定。评选结果 拟议的研究将作为未来病毒研究的基础 转录和复制。

DESCRIPTION (adapted from applicant's abstract): Bunyaviruses represent the largest family of negative stranded RNA viruses. Each contains a genome consisting of three RNA segments wrapped in a nucleoprotein complex. Most Bunyaviruses are propagated in an insect vector with the notable exception of Hantaviruses which are carried in rodents. Hantaan virus, the initial Hantavirus, was first shown to be the causative agent of Korean Hemorraghic Fever, a disease endemic in the Orient. Viruses closely related to Hantaan virus, however, have a worldwide distribution and to be associated with hemorraghic fever. With the recent unexpected outbreak of acute pulmonary syndrome in the Southwest, also caused by a hantavirus referred to as Sin Nombre Virus (SNV), the identification of additional cases in other regions of the country, and the characterization of several new species of hantavirus in North America, it is important to obtain a detailed understanding of the hantavirus life cycle. The long-term goals of the application are to elucidate the mechanisms of hantavirus mRNA synthesis and RNA replication. In this proposal, the applicant will focus on developing a topological map of the viral L protein. Due to the anticipated difficulty in obtaining large amounts of pure L protein sufficient for structural studies, we propose a novel approach to generating, identifying and characterizing active subdomains of the L protein. The results of the proposed studies will serve as the groundwork for future studies on viral transcription and replication.