Identification of hepatitis C virus binding proteins

丙型肝炎病毒结合蛋白的鉴定

• 批准号: 6596659
• 负责人: Michael Gale
• 金额: $ 7.34万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6596659
• 关键词: Vesiculovirus; genetic library; hepatitis C virus; liver cells; receptor binding; recombinant virus; tissue /cell culture; virus infection mechanism; virus protein; virus receptors

DESCRIPTION (provided by applicant): Hepatitis C virus (HCV) is a hepatotropic RNA virus that infects more than 200 million people worldwide. HCV is transmitted via percutaneous exposure to contaminated blood or blood products. Acute exposure to HCV most often leads to chronic infection characterized by persistent virus replication, hepatitis and the development of fibrosis and cirrhosis. The molecular basis for the hepatotropism of HCV has not been defined, in part, because of the lack of a suitable culture system by which to propagate native HCV infection. HCV binding and entry into the host cell is thought to occur through specific interactions of the HCV surface glycoproteins, E1 and E2, with surface proteins expressed on the target cell. We have adapted and developed new strategies by which to identify candidate HCV receptor proteins, and by which to assess the role of each candidate receptor in mediating the processes of virus binding and entry that direct HCV infection. We will utilize these novel strategies to investigate the hypothesis that HCV tropism is mediated by E1 and/or E2 glycoprotein interactions with liver-specific cell surface receptor proteins. In Aim 1 of this proposal we will utilize a cell-based expression/binding assay system to screen a liver-specific cDNA library for candidate cellular receptors that bind to one or both HCV glycoproteins. Aim 2 will employ a novel HCV-pseudotyped virus system to assess the role of each candidate receptor protein in supporting HCV binding and entry into the host cell. This pilot project will identify cellular HCV-binding proteins that direct viral tropism and that participate in the processes of HCV binding and entry. The proposed studies will provide novel insights into the HCV infectious cycle, and will establish a foundation for future work aimed at understanding the virus-cell interactions that confer HCV tropism and infection.

描述（由申请人提供）：丙型肝炎病毒（HCV）是一种嗜肝RNA病毒，感染全世界2亿多人。 HCV 通过经皮接触受污染的血液或血液制品传播。急性接触 HCV 通常会导致慢性感染，其特征是病毒持续复制、肝炎以及纤维化和肝硬化的发展。 HCV 亲肝性的分子基础尚未明确，部分原因是缺乏合适的培养系统来传播天然 HCV 感染。 HCV 结合并进入宿主细胞被认为是通过 HCV 表面糖蛋白 E1 和 E2 与靶细胞上表达的表面蛋白的特异性相互作用而发生的。我们已经调整并开发了新的策略，通过这些策略来识别候选 HCV 受体蛋白，并评估每个候选受体在介导病毒结合和进入直接 HCV 感染过程中的作用。我们将利用这些新策略来研究 HCV 趋向性是由 E1 和/或 E2 糖蛋白与肝脏特异性细胞表面受体蛋白相互作用介导的假设。在本提案的目标 1 中，我们将利用基于细胞的表达/结合测定系统来筛选肝脏特异性 cDNA 文库，以寻找与一种或两种 HCV 糖蛋白结合的候选细胞受体。目标 2 将采用新型 HCV 假型病毒系统来评估每种候选受体蛋白在支持 HCV 结合和进入宿主细胞中的作用。该试点项目将鉴定指导病毒趋向性并参与 HCV 结合和进入过程的细胞 HCV 结合蛋白。拟议的研究将为丙型肝炎病毒感染周期提供新的见解，并为未来旨在了解赋予丙型肝炎病毒趋向性和感染的病毒-细胞相互作用的工作奠定基础。