TRIM52抑制乙型脑炎病毒增殖的分子机制研究

乙型脑炎是一种重要的虫媒性人兽共患传染病，不仅威胁畜牧业的生产安全，而且严重危害人类的健康。乙型脑炎病毒(JEV)侵入中枢神经系统，导致脑部炎症和神经损伤，感染者大约25%-30% 死亡，50%的幸存者导致永久性中枢神经系统后遗症，而阐明JEV在宿主中复制机制有助于其预防和治疗。因此，本项目拟以TRIM52为研究对象，利用超表达、siRNA干扰、噬斑实验、荧光素酶报告系统、激光共聚焦、蛋白质互作等技术，从病毒和宿主两个层次研究：（1）TRIM52对JEV增殖及其复制周期（病毒吸附、侵入、复制、包装和释放）的影响；（2）TRIM52与JEV编码蛋白相互作用及其生物学效应；（3）TRIM52三维结构的解析；（4）TRIM52激活NF-kB信号分子机制及其与抑制JEV增殖之间的关系。该研究为JEV新型疫苗和抗病毒药物设计提供理论依据。

Japanese encephalitis(JE) is an important mosquito-borne zoonotic disease, not only threating the safety of animal husbandry, but also causing a major public health problem in humans. Japanese encephalitis virus (JEV), the significant etiological agent of JE, invades the central nervous system（CNS）and induces inflammation of the brain and neuron damage with a case fatality rate of 20%-30% and permanent neuropsychiatric sequelae in 50% of survivors. In this project, tripartite motif(TRIM) protein 52 will be studied by the methods of TRIM52 overexpression and siRNA knockdown, plaque forming unit test, Dual-luciferase assay, confocal microscopy technology, and protein-protein interaction. We hope to address the following questions: (1) How to restrict JEV propagation by TRIM52 and which stages of viral replication(including attachment, entry, transcription of viral genes and viral release from the cells) will be targeted; (2)The interactions between TRIM52 and JEV encoded proteins and its biological function; (3) Illuminate TRIM52 structure and the mechanism how to active the NF-κB signal pathways and its physiological relevance with antiviral activity against JEV. This study will provide new lights for future work on TRIM52-mediated antiviral fuction and the development of novel vaccine and anti-viral strategies against JEV.