病毒入侵是病毒感染人体的第一步；而固有免疫正是抗病毒的第一道防线，也是设计药物和疫苗的理想靶点。申请者对抗病毒固有免疫信号通路的调控机制进行系统研究，发现多个模式识别受体介导的信号通路的调节因子(如E3连接酶TRIP、TRIM38，芳香烃受体AhR等)，并阐明了作用的分子机制。病毒感染可诱导这些调节分子表达，抑制机体的抗病毒免疫反应，从而利于病毒逃避机体的免疫杀伤(免疫逃逸)。这一系列研究丰富了对抗病毒固有免疫调控及病毒免疫逃逸机制的认知。然而，病毒感染的固有免疫调控机制仍远未阐明，亟需展开深入研究。我们将继续围绕病毒感染与机体固有免疫调控这一关键科学问题，延续前期实验中的重要发现，进行系统深入研究。本项目将重点探讨病毒感染对糖代谢的影响及其机制、糖酵解转换对机体抗病毒固有免疫反应的调控及其机制，阐明病毒与宿主之间的相互作用及病毒的免疫逃逸机制，为药物设计和疫苗研制提供更为理想的靶点。

Viral invasion is the first and key step for viral infection. Innate immune system is the first line against viral infection and the optimal target for vaccine development and drug design. I focused on the mechanisms of modulation of the antiviral innate immune signaling and carried out a series of research. I have discovered that multiple molecules (such as E3 ubiquitin ligase TRIP, TRIM38 and aryl hydrocarbon receptor) were involved in the regulation of pattern-recognition receptors (PRRs) induced signal transduction and elucidated their underlying molecular mechanisms. Viral infection could induce the expression of these regulatory molecules and then inhibit host antiviral immune responses, thus facilitate immune escape of virus. These findings enriched the knowledge of mechanisms of innate immunity regulation and viral immune escape, and provided theoretical basis for the design of novel antiviral drugs and vaccines. However, the regulatory mechanisms of innate immune responses in viral infection remain largely unknown. In the follow-up researches, we will keep on focusing on viral infection and host innate immunity, a fundamental scientific issue in virology and immunology. In the present proposal, we will investigate the influence of viral infection on glucose metabolism and its mechanisms, the regulatory effects of glycolytic switch on host antiviral innate immune responses and its mechanisms. Through the study, we hope to elucidate the interaction between virus and host and the mechanisms of viral immune escape and supply ideal target for vaccine development and drug design.