Modeling HIV Rebound: Role of SIVmac251 Functional Reservoirs and Biomarkers of Reactivation

摘要 尽管长期以来完全抑制ART，但在大多数人中， 当ART被中断时。本提案中的研究将定义和量化 组织中功能性SIV潜伏库，以了解两者的贡献 CD 4 +T细胞和巨噬细胞向功能性病毒库和病毒反弹后 ART中断。SIVmac 251 ART抑制模型将用于定量 在CD 4 + T细胞和巨噬细胞中的功能性病毒储库，以评估它们对 病毒反弹将进行CD 4细胞的消耗和潜伏性储库的减少， 解决CD 4细胞是否是主要的HIV储存库或是否潜伏感染 巨噬细胞显著地促进HIV反弹。本方案中的项目将 1)确定静息CD 4 + T细胞和驻留巨噬细胞的差异贡献 抗逆转录病毒治疗中断后病毒反弹; 2）确定病毒来源 使用SIV前病毒基因组分析反弹;和3）使用计算建模和 分析SIV病毒反弹以了解艾滋病毒反弹。

Abstract Despite fully suppressive ART for long periods of time, HIV rebounds in the majority of individuals when ART is interrupted. Studies in this proposal will define and quantitate the functional SIV latent reservoirs in tissue to understand the contributions of both CD4+T cells and macrophages to the functional viral reservoir and viral rebound after ART interruption. The SIVmac251 ART suppressed model will be used to quantitate the functional viral reservoir in CD4+ T cells and macrophages to asses their contribution to viral rebound. Depletion of CD4 cells and reduction of the latent reservoir will be done to address whether CD4 cells are the major HIV reservoir or if latently infected macrophages significantly contribute to HIV rebound. The projects in this Program will 1) Identify the differential contribution of resting CD4+ T cells and resident macrophages to viral rebound after antiretroviral treatment interruption; 2) Identify the source of viral rebound using SIV proviral genome analysis; and 3) Use computational modeling and analyses of SIV virus rebound to understand HIV rebound.