本项目拟对HIV早期感染患者和正常人来源的CD4+T细胞进行miRNA表达谱比对，发现HIV感染可下调miR-29a和miR-29b的表达。进而观察miR-29对人和小鼠T淋巴细胞凋亡的调控作用，并明确其下游的靶基因以及上游的调控信号。初步实验结果表明，miR-29a antagomir可明显促进人CD4+T细胞的凋亡，过表达miR-29则能明显抑制免疫活化诱导的CD4+T细胞凋亡，提示miR-29的抗凋亡效应。候选靶基因检测发现HIV感染患者CD4+T细胞中的Bid mRNA水平显著高于正常人。在体外实验基础上，进一步观察miR-29在小鼠体内的抗凋亡效应。最后观察miR-29 mimic对HIV感染患者来源的CD4+T细胞，以及体外感染HIV病毒的正常人CD4+T细胞的抗凋亡作用，明确HIV感染过程中miR-29对CD4+T细胞的保护作用，以期为HIV感染的临床治疗提供新思路。

We focus on the difference between the microRNA profile of human CD4+T cells from patients with early HIV infection and that from healthy donors. The down-regulation of miR-29a and miR-29b was observed in CD4+T cells from patients with early HIV infection compared with healthy donors. This project will further explore the regulatory effect of miR-29 on the apoptosis of human and mouse T lymphocytes and the target genes of miR-29, as well as the upstream signaling that regulate the expression of miR-29. Our preliminary data showed that miR-29 antagomir treatment promoted the apoptosis of human CD4+T cells and overexpression of miR-29 significantly inhibited AICD of CD4+T cells, indicating the anti-apoptosis effect of miR-29. Bid, a putative target gene of miR-29, was up-regulated in CD4+T cells from patients with early HIV infection compared with healthy donors. On the basis of in vitro results, we will detect the activity of miR-29 in vivo. We will also observe the protection effect of miR-29 on apoptosis of the CD4+T cells from patients with HIV infection and the HIV infected CD4+T cells from health donor. These results may be helpful for the clinical therapy of HIV infection.