SIV VPX: STRUCTURE & FUNCTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目的主要目标是了解不同的猴免疫缺陷病毒VPX蛋白活性在病毒感染和粘膜传播后的传播中的作用。VPX如何影响SIV或HIV-2的感染和发病机制在很大程度上尚不清楚，尽管已知该蛋白在体外具有几种活性，可以影响巨噬细胞中的病毒复制，并可能调节宿主对病毒的免疫反应。此外，巨噬细胞在SIV和HIV-2致病机制中的作用尚不清楚。 目的：比较含野生型VPX基因的SIV克隆与功能突变的VPX基因的复制动力学。共有8只动物将被使用。动物将被分成4组，每组2只动物。每组都将被编码野生型VPX的SIVmne或突变型VPX基因(1个野生型和3个突变型)经直肠感染。在感染的整个急性期和尸检时，将定期检测血浆病毒载量。组织标本将用于通过原位杂交检查病毒传播情况。

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.