SIV VPX: STRUCTURE & FUNCTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The major goal of this project is to understand the role of different simian immunodeficiency virus Vpx protein activities in viral infection and dissemination following mucosal transmission. How Vpx influences infection and pathogenesis of either SIV or HIV-2 is largely unknown, although the protein is known to have several in vitro activities that can affect viral replication in macrophages and potentially modulate the host immune response to the virus. Moreover, the role of macrophages in SIV and HIV-2 pathogenesis remains unclear. Objective: To compare the replication kinetics of an SIV clone containing a wild type vpx gene versus mutant vpx genes disrupted for particular functions. A total of 8 animals will be used. Animals will be divided into 4 groups with two animals per group. Each group will be infected intrarectally with either SIVmne coding for wild type vpx or a mutant vpx gene (1 wild type and 3 mutants). Plasma viral loads will be examined at intervals throughout the acute stage of infection and at necropsy. Tissue specimens will be used to examine virus dissemination by in situ hybridization.