HIV-1的潜伏感染及其病毒贮存库是治愈HIV的主要障碍。研究表明：HIV-1编码的蛋白Nef在促进病毒复制中发挥着重要作用，但Nef对病毒复制的促进作用是否影响HIV潜伏感染的建立和再激活过程并不清楚。基于已有的外源性Nef激活了细胞株中潜伏的HIV-1的研究结果，且细胞株不如原代细胞更能反映体内的生理情况这一缺陷，病毒复制时自身产生的Nef是否具有类似作用还需要进一步研究。本项目拟通过不同方法建立的（由激活或静息的CD4+T细胞建立）并被本领域广泛接受的HIV潜伏感染的原代CD4+T细胞模型，明确Nef对HIV-1潜伏感染的建立和再激活的影响。为寻找参与该过程的相关因子，将应用RNA-seq技术高通量筛选介导Nef激活病毒潜伏的细胞效应因子和分子网络。本项目将为进一步解析HIV-1潜伏感染的病毒学和细胞学机制提供新的视点，并为最终清除或功能性治愈HIV-1感染提供新的思路和靶点。

A major hurdle in achieving a cure for human immunodeficiency virus (HIV)-1 is the existence of reservoirs of latent viral infection. Previous studies indicate that HIV-1 encoded viral protein Nef plays an important role in promoting viral replication. However, it remains elusive whether the positive influence of Nef on viral replication will affect the establishment and activation of viral latency. Based on the published results that exogenous Nef activated HIV-1 from latency in the latency model of cell lines, and the defect of cell lines not being as good as primary cells in terms of physiological relevance, further study is needed on whether the Nef produced during HIV replication has similar effects as exogenous Nef in activating latent HIV-1. In this project, we propose to investigate the influence of Nef on the establishment and re-activation of HIV-1 latency via two widely accepted primary CD4+T cell models of HIV-1 latency that are established by different methods (use of either resting or activated CD4+ T cells, respectively) . To find out the factors participating in this process, RNA-seq technique will be employed for high throughput screening of the cellular factors mediating Nef activation of HIV-1 latency. The findings from the proposed study will add to our understanding the virological and cellular pathogenesis of HIV-1 latency and ultimately developing mechanism-based novel strategies to eradicate or functionally cure HIV-infection.