Cellular receptor for the human polyomavirus, JCV

人多瘤病毒 (JCV) 的细胞受体

• 批准号: 6731202
• 负责人: Walter J Atwood
• 金额: $ 25.23万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6731202
• 关键词: HeLa cells; Polyomavirus hominis 2; affinity chromatography; astrocytes; binding proteins; cell membrane; confocal scanning microscopy; genetic library; glycosylation; human genetic material tag; human tissue; immunocytochemistry; immunoprecipitation; laboratory mouse; laboratory rabbit; mass spectrometry; monoclonal antibody; oligodendroglia; protein sequence; receptor binding; receptor expression; simian virus 40; transfection /expression vector; virus infection mechanism; virus receptors

DESCRIPTION (provided by applicant): The initial event in the life cycle of a virus is its interaction with receptors present on the surface of a cell. Understanding these interactions is important to our understanding of viral tropism, spread, and pathogenesis. The human polyomavirus, JCV, is the etiological agent of the fatal central nervous system (CNS) demyelinating disease, progressive multifocal leukoencephalopathy (PML). JCV has also been associated with several human tumors, including oligoastrocytoma and medulloblastoma. Following primary infection, JCV establishes a lifelong persistent infection in kidney and lymphoid tissues. In a minority of individuals, the virus spreads to the CNS, infecting both oligodendrocytes and astrocytes. The mechanisms that restrict JCV tropism for these cells and tissues and the mechanisms that allow for the spread of JCV from the periphery to the CNS are not understood. Our laboratory has been studying early events in the life cycle of JCV. We have determined that: 1. an N-linked glycoprotein containing terminal alpha (2-6) linked sialic acid is a critical component of the JCV receptor; 2. JCV and the related polyomavirus, SV40, do not share receptor specificity; and, 3. JCV, unlike SV40, enters cells by clathrin dependent receptor mediated endocytosis. The long term goals of our research are to define the role of virus receptors in mediating infection of cells and in determining viral tropism, spread, and pathogenesis in the infected host. Our working hypothesis, which is based on our previous work, is that JCV receptor interactions are critical determinants of viral entry, tropism, and spread within the host. We will address this hypothesis by asking the following questions: 1. What is the identity of the JCV receptor? 2. What are the cell and tissue distributions of JCV receptors? and 3. How does JCV penetrate the plasma membrane and target its genome to the nucleus? The data resulting from these studies will yield novel insights into the pathogenesis of JCV induced disease and may lead to novel therapies to prevent or treat these diseases.

描述（由申请人提供）：生命周期中的初始事件 病毒与细胞表面受体的相互作用。 了解这些相互作用对我们理解病毒的 向性、传播和发病机制。人类多瘤病毒，JCV，是 致死性中枢神经系统（CNS）脱髓鞘的病原体 进行性多灶性白质脑病（PML）。JCV也被 与几种人类肿瘤相关，包括寡星形细胞瘤和 髓母细胞瘤在初次感染后，JCV建立了一个终身的 肾脏和淋巴组织持续感染。在少数 在个体中，病毒传播到CNS，感染少突胶质细胞和 星形胶质细胞。限制JCV对这些细胞的嗜性的机制， 组织和机制，使JCV从周边扩散 中枢神经系统还不清楚。我们的实验室一直在研究 JCV的生命周期我们已经确定：1。N-连接糖蛋白 含有末端α（2-6）连接的唾液酸是 JCV受体; 2. JCV和相关的多瘤病毒SV 40不共享 受体特异性;和，3.与SV 40不同，JCV通过网格蛋白进入细胞 依赖受体介导的内吞作用。我们研究的长期目标 是为了确定病毒受体在介导细胞感染中的作用， 在确定病毒在受感染宿主中的嗜性、传播和发病机制方面。 我们的工作假设，这是基于我们以前的工作，是JCV， 受体相互作用是病毒进入、嗜性和 在宿主体内传播。我们将通过提出以下问题来解决这个假设 问题：1. JCV受体的身份是什么？2.什么是细胞 JCV受体的组织分布和3. JCV如何渗透到 质膜并将其基因组定位到细胞核？数据来源于 这些研究将对JCV诱导的发病机制产生新的见解， 并可能导致新的疗法来预防或治疗这些疾病。