Structure and function of Hepatitis C Virus glycoproteins

丙型肝炎病毒糖蛋白的结构和功能

• 批准号: nhmrc : 296200
• 负责人: A/Pr Heidi Drummer
• 金额: $ 32.06万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/structure-function-hepatitis-virus-glycoproteins/97781
• 关键词: Structure; function; Hepatitis; Virus; glycoproteins

Hepatitis C Virus infects approximately 200 million people world-wide and is the major cause of liver transplantation in the Western world. At present there is no vaccine and interferon alpha is the only therapy available and has only limited success in clearing viral infection. HCV is distantly related to flaviviruses eg tick-borne encephaltitis virus and yellow fever virus. All viruses attach to target cells using receptors to initiate the infection process. In the case of HCV, the envelope glycoproteins interact with as yet unknown receptors on the target cell surface resulting in the virus being internalized into endosomes. It is believed that the low pH environment of these endosomes triggers fusion of the viral and cellular membranes. After fusion the genome of the virus is released into target cells and begins the replication process. The actual events intitiating these processes are not understood for HCV but are believed to be mediated using two envelope glycoproteins. In this project we seek to gain a greater understanding of how viral fusion and entry occurs. We have new information regarding the localisation of the two envelope glycoproteins that will now enable us to carefully examine how viral fusion occurs. Using biochemical approaches, we will study their structure and function and examine how this relates to the well understood flavivirus mode of fusion and entry. We will test the functional consequences of altering the structure of the HCV envelope glycoproteins by developing in vitro assays of HCV fusion. Assays for HCV fusion are essential for future studies to identify viral receptors, examine the role of antibody in viral neutralization and can be used to test novel inhibitors of viral fusion and entry.

丙型肝炎病毒感染全球约2亿人，是西方世界肝移植的主要原因。目前还没有疫苗，干扰素α是唯一可用的治疗方法，在清除病毒感染方面仅取得有限的成功。丙型肝炎病毒与黄病毒有较远的亲缘关系，如蜱传脑炎病毒和黄热病病毒。所有病毒都通过受体附着在靶细胞上，从而启动感染过程。在HCV的情况下，包膜糖蛋白与靶细胞表面上迄今未知的受体相互作用，导致病毒被内化到内体中。据信，这些内体的低pH环境触发病毒和细胞膜的融合。融合后，病毒的基因组被释放到靶细胞中并开始复制过程。引发这些过程的实际事件对于HCV尚不清楚，但据信是使用两种包膜糖蛋白介导的。在这个项目中，我们试图获得更好的理解如何病毒融合和进入发生。我们有新的信息，关于本地化的两个包膜糖蛋白，现在将使我们能够仔细研究如何病毒融合发生。使用生物化学方法，我们将研究它们的结构和功能，并研究这与已充分理解的黄病毒融合和进入模式的关系。我们将通过开发HCV融合的体外测定来测试改变HCV包膜糖蛋白结构的功能后果。丙型肝炎病毒融合的测定是必不可少的，为未来的研究，以确定病毒受体，检查抗体在病毒中和的作用，并可用于测试新的抑制剂的病毒融合和进入。