I型干扰素（IFN-I）在宿主防御流感病毒感染中具有重要的作用，但是流感病毒逃逸IFN-I的机理仍然不清楚。我们的前期研究发现，H5N1、H9N2、H1N1和H7N9等感染后都能诱导PGRN上调；利用siRNA敲低PGRN表达后，流感病毒诱导的IFN-β增加；流感病毒感染PGRN基因缺失小鼠的肺泡灌洗液和血清中IFN-β升高；荧光素酶活性实验证实NEMO是PGRN调控IFN-I通路的关键信号分子。提示PGRN参与流感病毒诱导的IFN-β表达调控，但其分子机制还有待研究。本研究拟利用细胞模型和分子技术手段探讨PGRN对H9N2诱导IFN-β的负调控作用，并通过阐明PGRN、NEMO与A20之间的相互作用及其在H9N2诱导IFN-β中的作用，揭示IFN-β表达调控的新机制。本研究提出流感病毒通过诱导PGRN逃逸宿主监视，将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。

Type I interferons (IFN-I) play a critical role in host defense against influenza virus infection, and the mechanism of influenza virus to evade IFN-I responses remains to be fully understood. Our previous results demonstrated that the expression of PGRN was increased after influenza virus infection, including H5N1, H9N2, H1N, and H7N9. Using a PGRN gene knockdown assay and PGRN-deficient mice model, we demonstrated that virus-inducing IFN-β production was significantly increased in siRNA-transfected cells and in BALF and serum from PGRN-deficient mice. The luciferase assay results suggested that the inhibition of virus-induced IFN-I production by PGRN is dependent on NEMO. These data suggest that PGRN is involved in virus-induced IFN-β production, and the underlying molecular mechanisms 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 PGRN in the negative regulation of H9N2 virus-induced IFN-β. We will also elucidate the interaction between PGRN, NEMO and A20 and its role in the regulation of H9N2 virus-induced IFN-β. Our study will reveal a negative regulation of IFN-I signaling and identify a PGRN-mediated immune evasion pathway exploited by influenza virus. The project will also provide new sight for the mechanism of influenza virus infection and new target for the study of anti-viral drugs.