Exploring the role of microtubules in HIV-1 uncoating

描述（由申请方提供）：人类免疫缺陷病毒（HIV）膜与靶细胞膜融合后，发生一系列事件以建立感染。具体而言，在生命周期的早期，病毒必须逆转录其RNA基因组，并诱导该基因组转运到核膜，用于随后的核输入和整合。在病毒基因组核输入之前的某个时间点，病毒经历了知之甚少的脱壳过程，其定义为组装的衣壳结构从病毒核糖核蛋白复合物上拆卸。然而，脱膜的精确机制仍然难以捉摸。本申请的基础是这样的假设，即脱壳受到成熟的、组装的病毒衣壳晶格与微管马达蛋白和/或微管相关蛋白（MAP）之间的相互作用的影响。我们提供的证据表明，MT中断抑制HIV-1的脱壳，并建议利用检测方法来测量脱壳，活细胞成像试验和衣壳结合试验，以确定参与促进HIV-1脱壳的MAP。

DESCRIPTION (provided by applicant): Following human immunodeficiency virus (HIV) membrane fusion with the target cell membrane, a series of events occur to establish an infection. Specifically, early in the life cycle, the virus must reverse transcribe its RNA genome and induce the transport of this genome to the nuclear envelope for subsequent nuclear import and integration. At some point prior to the nuclear import of the viral genome, the virus undergoes the poorly understood process of uncoating, defined as the disassembly of the assembled capsid structure from the viral ribonucleoprotein complex. However, the precise mechanism of uncoating remains elusive. The foundation of this application is the hypothesis that uncoating is influenced by the interaction between the mature, assembled viral capsid lattice and microtubule motor proteins and/or microtubule- associated proteins (MAPs). We provide evidence that MT disruption inhibits HIV-1 uncoating and propose to utilize assays to measure uncoating, live cell imaging assays and capsid binding assays to identify the MAPs which are involved in facilitating HIV-1 uncoating.