Role of CD81 in hepatitis C virus infection

丙型肝炎是美国和世界范围内的一个主要健康问题。最近，在了解这种疾病的性质方面取得了相当大的进展。最近，在鉴定CD81作为丙型肝炎病毒的假定配体方面取得了相当大的进展。在过去的几年里，我们的实验室一直专注于CD81在细胞生长调节中的作用。本提案的总体目标是研究CD81在肝脏中可能有助于结合或进入丙型肝炎病毒的分子关联。我们假设CD81是分子复合体的一部分，该复合体在不同的身体组织之间存在差异。通过定义肝脏中这种复合体的成分并将其与其他组织进行比较，我们将开始揭示对病毒与CD81相互作用至关重要的特定分子相互作用。本提案旨在回答与丙型肝炎感染有关的三个问题。1)人体内哪些组织和细胞表达CD81？2)CD81是膜平面内分子复合体的一部分，该复合体的成分是否随组织而变化？3)是否有可能通过改变膜平面内的顺式相互作用或与丙型肝炎病毒上的E2蛋白的反式相互作用来阻断或改变丙型肝炎病毒与CD81的相互作用。这些信息将确定丙型肝炎的潜在靶点。通过比较表达CD81的细胞和能够结合病毒的细胞，我们将使用消减方法来确定细胞表面潜在的共受体分子。然后，这些信息可以用来检查丙型肝炎自然康复或注定要发展为慢性感染的患者群体中潜在的等位基因变异。一旦我们确定了导致丙型肝炎进展变化的基因差异或注定会发展为慢性感染的基因差异。一旦我们确定了导致丙型肝炎感染进展变化的遗传差异，我们就可能开发出更好地治疗这种疾病的治疗方案。

Hepatitis C is a major health problem within the United States and the world. Recently, considerable progress was made in understanding the nature of this disease. Recently considerable progress was made by identifying CD81 as a putative ligand of the Hepatitis C virus. For the past several years, our laboratory has focused on the role of CD81 in the regulation of cell growth. The overall goal of the present proposal is to investigate the molecular associations of CD81 in the liver that may contribute to binding or entry of the hepatitis C virus. We hypothesize the CD81 is part of a molecular complex which varies between different body tissues. By defining components of this complex in the liver and comparing this to other tissues, we will begin to reveal specific molecular interactions critical to the virus interactions with CD81. The present proposal is designed to answer three questions related to hepatitis C infections. 1) What tissues and cells within the human body express CD81? 2) Is CD81 part of a molecular complex within the plane of t he membrane, and does the components of this complex change from tissue to tissue? 3) Is it possible to block or alter the interaction of hepatitis C with CD81 by altering cis interactions within the plane of the membrane or trans interactions with the E2 protein on the hepatitis C virus. This information will define the potential targets for Hepatitis C. By comparing the cells expressing CD81 and t he cells capable of the binding the virus, we will use subtractive methods to identify potential co- receptor molecules on the surface of the cell. This information can then be used to examine potential allelic variation in populations of patients that either spontaneously recover from hepatitis C infection or that are predestined to develop chronic infections. Once we identify genetic differences that result in alterations in alterations in the progression of hepatitis C infection or that are predest8ned to develop chronic infections. Once we identify genetic difference that result in alterations in the progression of hepatitis C infections, we may be able to develop treatment protocols to better treat this disease.