Gag Protein Interactions Important for HIV Assembly

描述：该项目的长期目标是确定关键的 人类免疫缺陷病毒1型病毒与宿主蛋白的相互作用 (艾滋病毒-L)。Gag基因是唯一需要组装、运输、 并释放病毒颗粒，但有几种细胞蛋白参与其中。我们的 研究表明，亲环素A(CypA)控制成熟折叠 在下一次复制中增强病毒衣壳的能力 周而复始。TSG 101，一种利用内体运输所需的蛋白质 设备，可以促进有效的病毒颗粒释放。我们将确定 TSG 101-Gag相互作用在病毒复制中的功能意义 鉴定Tsg1O1受损细胞系中的GAG组装缺陷 表达(目标1)。我们将通过定义CYP A的角色来确定 细胞色素P450 A对成熟折叠的调控及其机制 CYP A诱导的病毒感染性结构变化的意义(目标2)。 第三个目标是确定参与GAG的细胞通路。 贩卖和集结。分子遗传、荧光的结合 将使用显微镜和蛋白质生物化学技术。

DESCRIPTION: The long-term goal of this project is to identify critical virus-host protein interactions of the human immunodeficiency virus type 1 (HIV-l). The gag gene is the only viral gene required for assembly, transport, and release of viral particles but several cellular proteins participate. Our studies suggest that cyclophilin A (CyP A) controls the maturational refolding of Gag to enhance the competence of the viral capsid in the next replicative cycle. Tsg 101, a protein required for trafficking using the endosomal apparatus, may promote efficient viral particle release. We will determine the functional significance of the Tsg 101-Gag interaction in virus replication by identifying the Gag assembly defect in a cell line impaired in tsg1O1 expression (Aim 1). We will determine the role of CyP A by defining the mechanism underlying CyP A control of maturational refolding and the significance of CyP A-induced structural changes for viral infectivity (Aim 2). The third goal is to identify cellular pathways that participate in Gag trafficking and assembly. A combination of molecular genetic, fluorescence microscopy, and protein biochemistry techniques will be used.