目前针对HIV感染的基因治疗方法主要以病毒基因表达和病毒转录复制所必须的细胞因子为靶点，但这些方法会出现潜在的毒性效应及诱导病毒抗性变异体。宿主天然免疫分子TRIM5α具有广泛的抗逆转录病毒活性，为寻找新的没有或具有较小毒性效应的基因治疗方法提供了新的希望。已报道猕猴TRIM5α基因多态性与宿主限制SIV复制的能力有关。但食蟹猴与中国恒河猴TRIM5α限制HIV-2复制的分子机理尚不明确。本项目在已有基础上，选择课题组已鉴定过的TRIM5α等位基因已知的猕猴群体，通过实时定量PCR、永生化细胞构建、病毒感染及融合蛋白表达与纯化等实验，剖析猕猴种间与种内TRIM5α不同等位基因与HIV-2的易感性，在此基础上研究TRIM5α不同蛋白功能域与病毒衣壳蛋白结合力差异，以探索宿主TRIM5α限制HIV-2复制的作用机理，为抗逆转录病毒药物的研发、猕猴SIV/HIV疾病模型的建立、疫苗研发提供依据。

At present, gene therapies for HIV infection mainly use the cytokine as target, which is necessary for viral gene expression and viral transcription and replication. However, potential toxicity and induced resistant virus variants will be exist when these methods are used. TRIM5α, a host innate immune molecule, has extensive antiretroviral activity that provides new approach for gene therapy with less or no toxic effect. It has been reported that several function domains of TRIM5α in the rhesus monkey have related with the capacity of host restricting the replication of SIV/HIV. But the mechanism that TRIM5α of cynomolgus macaque and Chinese rhesus restrict the replication of HIV-2 is not clear. Based on our previous study of TRIM5α allele in macaque population, here in this study, these methods including RT-PCR techniques, immortalized cell construction, virus infection and fusion protein expression and purification will be used to figure out what kind of TRIM5α allele affect the susceptibility of HIV-2 in interspecies and cross-species. We also try to find out which domain of TRIM5α protein determines its combination with the capsid protein. The mechanism that host TRIM5α restrict replication of HIV-2 will provide a new approach for development of anti-retroviral drugs, establishment of the macaque model for SIV/HIV and vaccine development.