乙脑病毒激活内质网应激反应的分子机制及致病性研究

项目名称： 乙脑病毒激活内质网应激反应的分子机制及致病性研究

项目编号： No.31460667

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 水产学、兽医学

项目作者： 孔令保

作者单位： 江西农业大学

项目金额： 50万元

中文摘要： 乙型脑炎（乙脑）是由乙脑病毒引起的一种严重危害我国人畜健康的传染病，其突出病理特征是脑组织炎症和细胞死亡。目前乙脑病毒感染致病的确切机制并不清楚，也没有有效的治疗药物。许多病毒通过激活内质网应激反应促进病毒的感染和致病。研究表明乙脑病毒激活内质网应激反应，有助于该病毒感染。但是，乙脑病毒激活内质网应激反应的分子机制和致病性目前知道很少。在前期研究乙脑病毒激活内质网应激反应的基础上，本课题拟研究：(1)体外实验分析乙脑病毒及其基因对内质网应激反应的三条信号通路（ATF6、IRE1和PERK信号通路）的调控；（2）体外实验分析乙脑病毒及其基因经内质网应激反应对炎症反应和细胞凋亡的调控；(3) 体内实验分析乙脑病毒对鼠脑组织内质网应激反应的激活及其致病性，从体外和体内，病毒及其基因水平上揭示乙脑病毒激活内质网应激反应的分子机制和致病性，为研发特异性乙脑防治药物提供新思路和新靶点。

中文关键词： 乙脑病毒；内质网应激反应；分子机制；致病性

英文摘要： Japanese encephalitis (JE) caused by Japanese encephalitis virus (JEV) is an infectious disease severely harming human and livestock in china, and its prominent pathological features are brain inflammation and cell death. The pathogenesis of JEV infection remains unclear, and there are no efficacious drugs against JE. Many viruses activate endoplasmic reticulum (ER) stress response, which promotes viral infection and pathogenicity. Previous studies indicate that JEV induces ER stress response, which is helpful to virus infection. However, the molecular mechanism and pathogenicity of ER stress response induced by JEV are still largely unknown. Based on our preliminary research on the activation of ER stress response by JEV, we here plan to investigate the following three aspects：（1） how JEV and its genes regulate three ER stress signal pathway (ATF6,IRE1 and PERK signal pathway) in vitro; （2） how JEV and its genes regulate inflammatory response and cell apoptosis via ER stress response in vitro; (2) the activation and pathogenicity of ER stress in the brain tissue of mice infected by JEV.These studies will reveal the molecular mechanism and pathogenicity of ER stress response induced by JEV through four respects including in vitro,in vivo, virus and viral genes, which will provide new insights and targets for the development of special anti-JE drugs.

英文关键词： Japanese encephalitis virus;endoplasmic reticulum stress response;molecular mechanism;pathogenicity