m38.5介导的细胞凋亡在巨细胞病毒性视网膜炎中对RIP1/RIP3坏死性凋亡及自我吞噬的调节研究

项目名称： m38.5介导的细胞凋亡在巨细胞病毒性视网膜炎中对RIP1/RIP3坏死性凋亡及自我吞噬的调节研究

项目编号： No.U1504812

项目类型： 联合基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 莫娟

作者单位： 河南省眼科研究所

项目金额： 27万元

中文摘要： 前期研究发现，巨细胞病毒基因m38.5转录成线粒体蛋白抑制Bax的活化，而Bax对坏死性凋亡通路的关键蛋白RIP1和RIP3有一定的调控作用，Bax/caspase 3介导的细胞凋亡通路与自我吞噬在巨细胞病毒感染中有交互对话。基于以上结果，本课题组假设：巨细胞病毒基因m38.5转录成凋亡抑制蛋白，通过调节Bax/caspase 3凋亡通路从而影响RIP1/RIP3坏死性凋亡通路，并与自我吞噬有相互作用。本项目拟从反应巨细胞病毒性视网膜炎真实状况的微环境出发，通过应用基因敲除和信号通路阻断等技术，探索m38.5介导的细胞凋亡通路、RIP1/RIP3坏死性凋亡通路和自我吞噬之间的具体作用机制，为临床控制免疫力低下人群中巨细胞病毒感染性视网膜炎的治疗提供新的理论和基础。

中文关键词： 巨细胞病毒性视网膜炎；m38.5；坏死性凋亡；细胞凋亡；自我吞噬

英文摘要： The previous studies have demonstrated that the mitochondrial protein encoded by Murine cytomegalovirus (MCMV) m38.5 inhibits Bax activity. Interestingly, expression of Bax affects the expression of RIP1 and RIP3 which are the key proteins in necroptosis. Moreover, there is a cross-talk between Bax/caspase 3-dependent apoptosis and autophagy during MCMV infection. We therefore hypothesize that mitochondrial protein encoded by MCMV m38.5 regulates RIP1/RIP3-dependent necroptosis by regulating Bax/caspase 3-dependent apoptosis, and there is a relationship between apoptosis, necroptosis and autophagy. Based on the models which can reflect the real microenvironment in MCMV retinitis, our project uses techniques including gene knockout and inhibition of signaling pathways to investigate the relationship and involved mechanisms between m38.5 encoded protein-mediated apoptosis, RIP1/RIP3-dependent necroptosis and autophagy during MCMV retinitis, which provides the basic theory for the control of clinical Human CMV retinitis among immunosuppressed peoples.

英文关键词： MCMV retinitis;m38.5;necroptosis;apoptosis;autophagy