高效抗逆转录病毒治疗(HAART)AIDS后，仍有20%的患者表现为免疫重建不良，其发生机制不清。转录因子ETV2是课题组最新鉴定的AIDS免疫重建不良的关键因子，其在INRs患者异常高表达并抑制CD4+T周期进程。后续研究发现：1）ETV2直接结合IFIT3启动子区并激活其转录；2）IFIT3激活YAP/TAZ信号通路。本研究拟阐明ETV2通过IFIT3激活YAP/TAZ通路抑制CD4+T细胞周期进程参与AIDS免疫重建不良的分子机制。课题将从：1）研究YAP/TAZ通路在IFIT3抑制CD4+T细胞周期中的重要作用；2）研究ETV2促进IFIT3转录的分子机制；3）探索Hippo通路抑制剂促CD4+T细胞周期和增殖的有效性，三个方面展开研究。本研究将从基因层面揭示AIDS免疫重建不良发生的分子机制，为临床治疗AIDS提供新思路和新靶点。

After highly effective antiretroviral therapy (HAART) for AIDS, 20% of the patients still show incomplete immune reconstitution, and the mechanism is unclear. The transcription factor ETV2 is the key factor for the incomplete immune reconstitution of AIDS, which was recently identified by our research group. It is highly expressed in INRs and inhibits the CD4+T cell cycle. The following studies showed that: 1) ETV2 directly binds to the IFIT3 promoter and activates its transcription; 2) IFIT3 activates the Hippo-YAP/TAZ signaling pathway. This study aims to elucidate the molecular mechanism that ETV2 promotes the transcription of IFIT3, activates the phosphorylation of YAP/TAZ, a downstream factor of Hippo pathway, and inhibits the cell cycle of CD4+T cells. This research will focus on: 1) the important role of YAP/TAZ pathway in the inhibition of CD4+T cell cycle by IFIT3; 2) the molecular mechanism of ETV2 promoting the transcription of IFIT3; 3) the effectiveness of Hippo pathway inhibitor in promoting CD4+T cell cycle and proliferation. This study will reveal the genetic mechanism of the incomplete immune reconstitution of AIDS, and provide new ideas and targets for clinical treatment.