Analysis of the human immnunodeficiency virus budding site

人类免疫缺陷病毒（HIV）1型组装为未成熟的非感染性颗粒，其经历细胞外成熟为感染性病毒粒子。病毒装配伴随着在受感染细胞的质膜上的粘附而发生。颗粒的形成是由病毒Gag多蛋白介导的，被认为发生在脂筏，并需要细胞ES CRT-机械的作用，以促进释放的出芽病毒粒子。在这个项目中，我们计划与K，Grünewald（MPI Martinsried）的小组一起通过冷冻电子断层扫描确定HIV-1出芽位点和出芽停滞颗粒的结构。此外，我们将分析的贡献，锥形肌动蛋白层的HIV-1出芽使用生化和超微结构的方法和治疗与F-肌动蛋白稳定和不稳定的药物相结合。最后，我们将研究脂筏，特定的脂质和蛋白磷酸化的HIV-1颗粒形成的贡献。这些研究将有助于对HIV-1出芽位点的详细结构和分子理解，并可能有助于寻找抗病毒治疗的新策略。

Human immunodeficiency virus (HIV) type 1 is assembled as immature, non-infectious particle which undergoes extracellular maturation to the infectious virion. Virus assembly occurs concomitant with envelopment at the plasma membrane of the infected cell. Particle formation is mediated by the viral Gag polyprotein, is presumed to take place at lipid rafts, and requires the action of cellular E S CRT-machinery to facilitate release of the budding virion. In this project, we plan to determine the structure of the HIV-1 budding site and of budding-arrested particles by cryo-electron tomography together with the group of K, Grünewald (MPI Martinsried). In addition, we will analyze the contribution of the conical actin layer to HIV-1 budding using a combination of biochemical and ultrastructural approaches and treatment with F-actin stabilizing and destabilizing drugs. Lastly, we will examine the contribution of lipid rafts, specific lipids and of protein phosphorylation to HIV-1 particle formation. These studies should lead to a detailed structural and molecular understanding of the HIV-1 budding site and may aid in the search for new strategies for antiviral therapy.