广西HIV感染长期不进展与病毒基因突变及修饰的相关性研究

项目名称： 广西HIV感染长期不进展与病毒基因突变及修饰的相关性研究

项目编号： No.81460510

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 沈智勇

作者单位： 广西壮族自治区疾病预防控制中心

项目金额： 45万元

中文摘要： HIV感染长期不进展者约占HIV感染总人群的2-9%。这些长期不进展者已经成为HIV 自发病毒控制研究领域的研究热点。CRF01_AE 亚型与HIV快速进展有关, 我们广西流行的亚型以CRF01_AE和CRF08_BC为主, 然而在广西有90例存活的长期不进展者。影响HIV感染进程的因素是多方面的，其中可能涉及到病毒缺陷和表观修饰等因素。曾经有少量的相关研究表明HIV的基因突变和基因修饰与疾病发展的进程有关系，但是还存在很多争议。我们将比较分析广西长期不进展者和对照组病人外周血单核细胞中病毒的突变及DNA甲基化情况，进行病毒分型，分析它们与病毒载量、CD4水平的相关性，探讨病毒突变及表观修饰对HIV感染疾病进程的影响。本次研究有可能为HIV疫苗研究以及抗病毒治疗策略提供一定的实验依据。

中文关键词： HIV；CRF01_AE；基因突变；DNA甲基化；长期不进展

英文摘要： The group of HIV positive long term non-progressors（LTNPs）comprises 2-9 percent of the total HIV population. These individuals have become the center of many studies to identify mechanisms of spontaneous viral control. CRF01_AE subtype was associated with fast progression to AIDS. CRF01_AE, along with CRF08_BC, is the dominant strain in Guangxi province. However,there are 90 cases survival LTNPs in Guangxi. Several factors may take part in the control of HIV disease progression,including defective viral strains and epigenetic modifications. Previous relatively studies have associated gene mutation and epigenetic modification of provirus with disease progression, but there are controversial conclusions. We will detect the viral gene mutation and DNA methylation patterns in peripheral blood mononuclear cells (PBMCs) from LTNPs, compared with patients in whom HAART resulted in the suppression of plasma viremia。we will also identify the subtypes, detect the viral load and levels of CD4. We will analyse more rigorously whether particular proviral mutation and epigenetic modification are associated with HIV disease progression. This study will be possible to provide experimental basis and have important implications for strategies aimed at vaccine research and antiretroviral therapy.

英文关键词： HIV;CRF01_AE;viral mutation;DNA methylation;long term non-progression