HIV-1感染者髓样树突细胞LILRBs受体mRNA前体选择性剪接及其功能分化的研究

项目名称： HIV-1感染者髓样树突细胞LILRBs受体mRNA前体选择性剪接及其功能分化的研究

项目编号： No.81201294

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 牟丹蕾

作者单位： 首都医科大学

项目金额： 23万元

中文摘要： 潜伏的HIV是ART治疗的瓶颈，DC在HIV潜伏感染中的作用日渐彰显。业已证实，mDC表达的抑制性HLA-I类分子受体- - LILRBs中的不同成员在HIV-1感染所致的DC抗病毒免疫功能缺陷中发挥不同作用，但其中精细的分子调控机制尚未阐明。我们前期工作发现，在HIV-1慢性感染者髓单核细胞存在编码蛋白质结构和功能各异的LILRB2 mRNA前体优势剪接异形体。本研究以此为切入点，首先确定不同病期、不同进展速度的HIV1感染者外周血mDC中LILRBs mRNA前体的优势剪接异形体；然后对其编码蛋白质结构和功能进行分析鉴定；最后初探其在HIV-1储存库建立和疾病进展中作用。这将为理解HIV潜伏感染和免疫致病的分子机制提供新视点，有助于为清除潜伏HIV-1的miRNAs策略提供新靶标，并有望为开展DC免疫治疗和研发HIV DC疫苗提供新思路。

中文关键词： 人类免疫缺陷病毒-1；白细胞免疫球蛋白样受体；选择性剪接；树突细胞；

英文摘要： HIV Latency is the bottleneck problem in ART treatment. DCs, as target cells and the reservoris for HIV-1, assume an increasingly important role in HIV Latency. The myelomonocytic(mDC) inhibitory HLA class I receptor LILRB2 involved in anti-viral immune deficiency of mDC in HIV-1 infection, while the selective and regulated expression of LILRB1 and LILRB3 helps to maintain unique antigen-presenting properties of circulating mDC in HIV-1-infected elite controllers, but the precise molecular mechanisms are ill defined. In our previous work, we found that there exist three kinds of dominant alternative pre-mRNA splicing variants of LILRB2 which encode proteins with different structure and function in mDC of HIV-1 chronic infection. In this study, we will predict and determine dominant alternative pre-mRNA splicing variants of mDC LILRBs in different stages and different rate of disease progression of HIV-1 infection, and then analyze and identify structure and function proteins encoded by these splicing variants. At the meantime, we also plan to observe and investigate their role in reservoris establishment and disease progression in HIV-1 infection. This study will provide important new insight into the molecular mechanisms of HIV latent infection and immune pathogenesis, and helps to explore new targets of miRNAs

英文关键词： Human Immunodeficiency Virus-1；Leukocyte Immunoglobulin-Like Receptors；Alternative Splicing；Dendritic Cell；