FUNCTIONS OF RETROVIRAL RECEPTORS TRANSPORTERS

描述(改编自申请人的摘要)：蜂窝传送器 蛋白质已被确定为逆转录病毒的受体。这个 两性小鼠逆转录病毒受体与长臂猿白血病 病毒是相关的磷酸盐转运体(分别为RAM-1和GLVR-1)。 亲生性小鼠逆转录病毒的受体是一种碱性氨基酸 运输机(CAT-1)。这些研究的总体目标是分析 这些受体/转运体的结构和双重功能 了解它们在病毒致病机制中的作用并改进它们的使用 用于基因传递。提出了五个具体目标：1)了解 结构、翻译后修饰、细胞分布和 RAM-1和GLVR-1蛋白的作用机制。特别的 人们感兴趣的是磷酸化在增强细胞外信号转导通路活性中的作用 Ram-1蛋白在运输和感染中都有作用。2)确定以下因素 在功能和/或物理上与RAM-1交互并研究功能 在这些互动中。3)追求能协同的宿主细胞因子(S) 受体在导致细胞和病毒融合的途径中 膜。提出了一种多价分子组装模型。 病毒受体簇可能是完成这一途径所必需的4) 确定抗病毒药物，磷酸类似物，福斯卡奈特 (磷酸甲酸盐)抑制RAM-1和GLVR-1转运体的活性。5) 分析糖基化在阻断仓鼠细胞感染中的作用 亲性和两性小鼠逆转录病毒。

DESCRIPTION (Adapted from the applicant's abstract): Cellular transporter proteins have been identified as the receptors for retroviruses. The receptor for the amphotropic murine retroviruses and Gibbon ape leukemia virus are related phosphate transporters (RAM-1 and GLVR-1, respectively). The receptor for the ecotropic murine retrovirus is a basic amino acid transporter (CAT-1). The overall goal of these studies are to analyze the structure and dual functions of these receptors/transporters in order to understand their role in viral pathogenesis as well as to improve their use for gene delivery. Five specific aims are proposed: 1) Understand the structures, post-translational modifications, cellular distributions, and mechanisms of function of the RAM-1 and GLVR-1 proteins. Of particular interest is the role of phosphorylation in enhancing the activities of the RAM-1 protein in both transport and infection. 2) Identify factors that functionally and/or physically interact with RAM-1 and study the functions of these interactions. 3) Pursue host cell factor(s) that could collaborate with receptors in a pathway that leads to fusion of the cell and viral membranes. A model is presented that the assembly of multivalent virus-receptor clusters may be necessary for completion of this pathway 4) Determine whether the antiviral drug, phosphate analog, forscarnet (phosphonoformate) inhibits the RAM-1 and GLVR-1 transporter activities. 5) Analyze the role of glycosylation in blocking infection of hamster cells by ecotropic and amphotropic mouse retroviruses.