Exploring the role of microtubules in HIV-1 uncoating

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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.