Cell-in-cell介导非易感细胞病毒感染及其免疫逃逸机制研究

项目名称： Cell-in-cell介导非易感细胞病毒感染及其免疫逃逸机制研究

项目编号： No.81471578

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王小宁

作者单位： 中国人民解放军总医院

项目金额： 75万元

中文摘要： Cell-in-cell是指一个或多个细胞主动钻入其他细胞，并产生生物学效应的过程，成为近年关注的新热点。我们发现携带病毒的淋巴细胞（EBV或HIV）可以通过cell-in-cell过程将病毒带入其非易感上皮细胞，并产生持续感染，命名为in-cell infection，为研究病毒持续感染、变异和致癌提供了全新模式，也为病毒免疫逃逸、病毒致上皮细胞癌变规律提供了独特的切入点。本课题聚焦cell-in-cell自身诱导上皮细胞染色体不稳定与其继发介导的病毒感染再次诱导上皮细胞染色体不稳定的双重打击效应对被感染上皮细胞免疫基因群改变和上皮-间充质细胞转化（EMT）的影响，解析感染细胞和EMT细胞逃逸免疫监视的机理，不但对于病毒持续感染的防治提供新思路，也为进一步解析单个细胞水平上上皮细胞-癌细胞演化规律提供了独具特色的研究切入点，具有重要的基础和临床研究价值。

中文关键词： 抗病毒免疫；信号通路；天然免疫

英文摘要： Cell-in-cell process is a unique phenomenon that one or more living cells penetrate into another cell with the alteration of biological function of both host and invading cells, which arouse great interests. Recently,we have discovered a novel virus infection pathway that the invasion of lymphocytes carring virus (EBV or HIV)into unsusceptible epithelial cells led to high efficacy of virus infection to unsusceptible epithelial cells. Unlike conventional cell-to-cell infection pathway, this process was initiated by cell-in-cell structure formation and the infection occurred inside the host cell, which we defined in-cell infection model. We supposed that this infection model would not noly be associated with infection persistence, genome variation and tumorigenesis, but also be engaged in the immune escape of virus and epithelia-mesenchymal transition (EMT). In the present study, we intend to highlight the possibility that in-cell infection induces chromosome instability mediated by both cell-in-cell formation and subsequent virus infection, which in turn leads to the alteration of genome constitution and EMT efficacy of epithelial cells. To dissect the exact mechanisms of in-cell infection process and its significance will provide new theory to elucidate the epithelial cell-tumor cell transmission process, as well as strategy for the prevention of virus infection.

英文关键词： cell-in-cell;in-cell infection;NK cell;EMT;canceration