FUNCTIONS OF RETROVIRAL RECEPTORS TRANSPORTERS

描述（改编自申请人摘要）：细胞转运蛋白 蛋白质已被鉴定为逆转录病毒的受体。 的 嗜中性鼠逆转录病毒受体与巨猿白血病 病毒是相关的磷酸盐转运蛋白（分别为RAM-1和GLVR-1）。 亲嗜性鼠逆转录病毒的受体是一种碱性氨基酸 转运蛋白（CAT-1）。 这些研究的总体目标是分析 这些受体/转运蛋白的结构和双重功能， 了解它们在病毒发病机制中的作用，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， RAM-1和GLVR-1蛋白的功能机制。 特别 感兴趣的是磷酸化在增强细胞活性中的作用。 RAM-1蛋白在运输和感染中的作用。 2)确定 在功能上和/或物理上与RAM-1相互作用，并研究其功能 这些互动。 3)寻找可以协作的宿主细胞因子 在导致细胞和病毒融合的途径中有受体 膜。 提出了一个多价体组装的模型， 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，磷酸盐类似物，Forscarnet （膦甲酸酯）抑制RAM-1和GLVR-1转运蛋白活性。 第五章） 用免疫荧光法分析糖基化在阻断仓鼠细胞感染中的作用 亲嗜性和兼嗜性小鼠逆转录病毒。

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.