DNA受体IFI16在A型流感病毒感染中的作用和机制研究

DNA受体IFI16在多种DNA病毒感染中发挥重要作用，但是IFI16在流感病毒感染中的作用还未见报道。前期研究发现，流感病毒H1N1/PR8感染后可以诱导人源细胞系中IFI16和小鼠肺组织中IFI16鼠同源蛋白p204的表达；IFI16基因过表达抑制PR8的复制，而基因缺失则增强小鼠对PR8的易感性；IFI16能够上调PR8诱导I型干扰素（IFN-I）的产生和相关信号分子的表达。这些结果提示IFI16参与流感病毒感染过程，但其分子调控机制还不清楚。本研究拟利用细胞模型和分子技术手段探讨IFI16在流感病毒感染中的作用，分析IFI16对流感病毒诱导IFN-I的调控作用，阐明IFI16调控IFN-I通路的关键信号分子和作用机制。本研究不仅丰富了IFI16的生物学功能，而且进一步完善和发展了抗病毒天然免疫信号网络的理论，并为流感病毒感染机制的解析和抗病毒药物的设计等提供新的思路。

IFI16 is a DNA sensor and plays a critical role in host defense against a variety of DNA virus infection, and the mechanism of IFI16 in influenza virus infection remains to be fully understood. Our previous results demonstrated that the expression of PGRN was increased in HEK293 and THP-1 cells after H1N1/PR8 infection, and the expression of p204 was also induced in mouse lung tissues after virus infection. Overexpression of IFI16 gene inhibits PR8 virus replication, whereas p204 deficiency makes mice more susceptible to PR8 virus infection. Overexpression of IFI16 gene significantly increases PR8 virus-induced gene expression of type I interferons (IFN-I) and associated signal molecules. These data suggest that IFI16 may be involved in the pathogenesis of influenza virus infection, and the underlying molecular mechanisms still need to be further elucidated. In this project, we plan to use several cell models in combination with varieties of molecular techniques to explore the functions of IFI16 in influenza virus infection. We will also investigate the role of IFI16 in the regulation of influenza virus-induced type I interferons and the crucial targets and molecular mechanism involved in IFI16-mediated type I interferons production. Our study will expand the biological functions of IFI16, improve and develop the theory of antiviral innate immune responses, and provide new sight for the mechanism of influenza virus infection and new target for the study of anti-viral drugs.