Cellular receptor for the human polyomavirus, JCV

描述(由申请人提供)：生命周期中的初始事件 病毒是它与存在于细胞表面的受体相互作用。 了解这些相互作用对我们理解病毒很重要 性向、传播和发病机制。人类多瘤病毒，JCV，是 致死性中枢神经系统脱髓鞘的病原学研究 进行性多灶性白质脑病(PML)。JCV也一直在 与几种人类肿瘤有关，包括寡星形细胞瘤和 髓母细胞瘤。在初次感染后，JCV建立了终生 肾脏和淋巴组织中的持续性感染。在少数人中 病毒在个体中传播到中枢神经系统，感染少突胶质细胞和 星形胶质细胞。限制这些细胞JCV趋向性的机制和 允许JCV从外周传播的组织和机制 对中枢神经系统的影响尚不清楚。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-连接的糖蛋白 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SV40不共享 受体特异性；3.JCV与SV40不同，是通过网状蛋白进入细胞的 依赖受体介导的内吞作用。我们研究的长期目标是 是为了确定病毒受体在介导细胞和 在确定病毒在受感染宿主中的嗜性、传播和致病机制方面。 我们的工作假设是，基于我们以前的工作，JCV 受体相互作用是病毒进入、趋向性和 在宿主体内传播。我们将通过询问以下问题来解决这一假设 问题：1.JCV受体的身份是什么？2.细胞是什么 以及JCV受体的组织分布？3.JCV是如何渗透到 质膜并将其基因组定位于细胞核？产生的数据来自 这些研究将对JCV的发病机制提供新的见解。 并可能导致预防或治疗这些疾病的新疗法。

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.