EV71是引起婴幼儿手足口病的重要病原体，其宿主抗感染免疫应答机制尚未阐明。申请人前期研究发现EV71和UV-EV71能够引起宿主细胞形成TLR2/TLR4异源二聚体且具有正常的细胞因子应答，因此推测EV71衣壳蛋白可能经TLR2/TLR4异源二聚体介导细胞因子反应。本课题将以EV71衣壳蛋白与TLR2/TLR4异源二聚体互作为主线，通过中和抗体实验、CO-IP、免疫印迹、质粒转染、报告基因分析和细胞因子测定等方法，明确能够有效活化细胞因子应答的EV71衣壳蛋白，阐明EV71衣壳蛋白经TLR2/TLR4异源二聚体活化免疫应答，揭示EV71衣壳蛋白、TLR2与TLR4互作的分子机制。本课题可能揭示宿主细胞抗EV71感染的一个新机制。

EV71 is the major pathogen of hand, foot, and mouth disease among children less than five years. Presently little is known about the mechanisms of host antiviral innate immunity against EV71 infection. Our previously studies showed that EV71 and UV-EV71 induced the formation of TLR2/TLR4 heterodimer and along with normal cytokine response. We conclude that EV71 capsids maybe activate cytokine response via TLR2/TLR4 heterodimer based on our previously results. In this project, we will focus on the interaction between EV71 capsid and TLR2/TLR4 heterodimer through using blocking experiment by neutralizing antibodies, co-immunoprecipitation, western blot, plasmid transfection, reporter gene assay and enzyme-linked immunosorbent assay. These studies will determine the EV71 capsid protein which can activate cytokine response effectively, illuminate EV71 capsid protein activating cytokine response via TLR2/TLR4 heterodimer, reveal molecular mechanism of the interaction between EV71 capsid protein and TLR2/TLR4 heterodimer. This project may provide a novel mechanism of host antiviral innate immunity against EV71 infection.