中国人HLA-I基因多态性与HIV-1免疫逃逸变异的相关性研究

HIV-1的变异在机体免疫压力作用下呈现一定的规律性。阐明这种变异模式对于研究机体特异性免疫机制、寻找特异性免疫表位、研究有效的HIV-1疫苗至关重要。HLA-I分子为机体特异性细胞免疫反应提呈表位，其多态性直接影响机体的免疫应答效率。大量研究显示HLA-I基因多态性与HIV-1的感染和复制相关。不同人群的HLA-I分子具有很大的差异，本研究拟以中国的HIV-1感染者为研究对象，对HLA-I遗传背景不同的个体进行横断面研究，对HLA-I遗传背景相似的个体进行队列研究，结合运用生物信息学和统计学方法，分析HLA-I基因多态性和HIV-1感染者体内病毒基因序列变异的关系，观察HIV-1变异模式，筛选、鉴定能够引起病毒复制能力降低的HLA-I限制性免疫逃逸突变，为研究适合我国人群使用的HIV-1疫苗奠定基础。

Host immune presssure always leads to typical escape mutations of HIV-1. Study on the pattern of HIV-1 mutation under host immune pressure will be helpful for illustration of host specific immunol mechanism, finding of specific immunol epitope, and success of HIV-1 vaccine. HLA-I plays important role in presentation of epitopes to cytotoxic T cells. The polymorphism of MHC-I gene, which codes HLA-I protein, has important effects on host immune response. Many studies suggested close relationship between MHC-I polymorphism and HIV-1 infection or replication. Since much difference of HLA-I protein could be found among different populations, Chinese participants will be enrolled as the study subjects. Several epidemiological studies , including cross-sectional study basing on participants containing different HLA-I genetic backgroud, cohort study basing on populations containing similar HLA-I genetic background, will be fulfilled as the study design. Bioinformatic and statistical methods will be combined to analyze the correlation between host HLA-I genetic polymorphism and HIV-1 genetic mutations, observe the specific evolution pattern of HIV-1, screen and identify mutations in epitopes targeted by CTL mediated by specific HLA-I. Then those mutations which can cause the decrease of viral repliation fitness will be identified. The results of the study will be important for the study of HIV-1 vaccines which can be used in Chinese population.