巨噬细胞在HIV-1的潜伏感染，病毒传播及免疫反应等过程中具有重要作用，但是病毒感染巨噬细胞的分子机制并不清楚。我们发现TRIM11抑制HIV-1复制的整合前环节，而HIV-1感染巨噬细胞的必需因子Vpr能够调控TRIM11的表达量。有报道证明TRIM11的表达水平与病毒滴度成负相关，因此我们推测，Vpr通过调控TRIM11而影响病毒感染巨噬细胞。该项目拟用PMA诱导可分化为巨噬细胞的THP-1细胞，在过量表达或敲除TRIM11后感染病毒，检测病毒的感染复制性，分析受影响的具体环节；共表达TRIM11缺失突变体与Vpr后感染病毒，确定TRIM11的关键功能域及Vpr调控TRIM11在病毒感染巨噬细胞中的意义；进一步解析Vpr调控TRIM11的分子机理，最终阐明Vpr通过调控TRIM11影响HIV-1感染巨噬细胞的分子机制，为更好的理解HIV-1在巨噬细胞中的感染复制机制提供理论基础。

Macrophages play important roles in latency, spreading and immune response of HIV-1 infection, but the molecular mechanisms of HIV-1 infection to macrophage are still unclear. We found that TRIM11 can inhibit the replication of HIV-1, and mainly work on the pre-integration step. Further experiments showed that the expression of TRIM11 can be regulated by HIV-1 accessary protein Vpr, which is known to be the essential protein for virus infection to macrophage. The report proved that TRIM11 expression levels were negatively correlated with viral titer recently, so we asked whether the regulation of TRIM11 by Vpr affect HIV-1 infection to macrophage. In this study we will use THP-1 cells, which can be induced to differentiate to macrophage by PMA treatment, to answer our qustion. We will establish the TRIM11 overexpression or knockdown THP-1 cell line, and detect the replication of virus after HIV-1 infection. Then a series of TRIM11 deletion mutations will be constructed to identify the important domains to viral replication, and co-expression of them with Vpr to determine whether the regulation of TRIM11 by Vpr affect HIV-1 infection to macrophage. Furthermore, we will use the VprBP knockdown cells or the E3 ubiquitin enzyme inhibitor to investigate the molecular mechanism of the regulation of TRIM11 by Vpr. Finally we try to clarify the roles of regulation of TRIM11 by Vpr on HIV-1 infection to macrophages. We hope our research would give some suggestions on the mechanism of HIV-1 infection to macrophage and some new ideas on the therapy and eradication HIV-1.