EV71病毒感染介导Sam68调控PI3K/AKT信号通路的分子机制

项目名称： EV71病毒感染介导Sam68调控PI3K/AKT信号通路的分子机制

项目编号： No.31300145

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 张华

作者单位： 黑龙江八一农垦大学

项目金额： 23万元

中文摘要： 肠道病毒71型(Enterovirus 71)属于小RNA病毒科，肠道病毒属，为无囊膜的单股正链RNA病毒，主要引起婴幼儿手足口病。在病毒侵染早期，EV71激活宿主细胞PI3K/AKT信号通路以延迟细胞凋亡，但激活机制尚不清楚。Sam68是一种STAR接头蛋白，属于c-Src/PI3K通路信号分子，在细胞周期、增值分化及信号转导中发挥重要作用。前期研究发现：EV71感染细胞后，病毒3C蛋白酶介导Sam68出核；基因沉默sam68后，显著抑制 PI3K/AKT的激活及病毒复制；CoIP进一步证实Sam68与PI3K P85亚基存在相互作用，这些结果说明Sam68为PI3K/AKT上游重要的调控分子。本研究将采用过表达、蛋白互作、突变分析、RNA干扰等技术，在基因、转录和蛋白水平，研究Sam68调控PI3K/AKT信号通路的分子机制，为进一步阐明EV71病毒感染的分子机理奠定相关的基础。

中文关键词： EV71病毒；Sam68；PI3K/Akt；信号通路；分子机制

英文摘要： Enterovirus 71 (EV71) is a non-enveloped single-(+) strand RNA virus of the Picornaviridae family, genus Enterovirus. EV71 infection mainly caused several epidemics of hand-foot-and-mouth in young children. Previous reports suggested that EV71 activated PI3K/AKT pathway to delay host cell apoptosis in an early infection. However, the potential mechanisam remains unclear. Sam68 belongs to members of the STAR family (signal transduction and activation of RNA metabolism)and c-Src/PI3K signal pathway, which participates in cell cycle, proliferation and signal transduciton. Our previous study indicated that EV71 3C protease triggered the export of Sam68 from nucleus during virus infection. The activation of PI3K/AKT was significantly down-regulated by silence of sam68 gene. At the same time, the replication of EV71 was notably inhibited. The Co-Immunoprecipitation (CoIP)further confirmed the interaction between Sam68 and PI3K p85 subunit. These data suggested that Sam68 plays an importan role in modulating activation of PI3K/AKT signal pathway in the upstream. Next, we will use overexpression, protein interaction, mutation analysis and RNA interfere, and so on, to study molecular mechanism of PI3K/AKT activation modulated by Sam68 at gene level, transcritional level and protein level, which will further provides a ne

英文关键词： Enterovirus 71；Sam68；PI3K/Akt；signal pathway；molecular mechnasim