深入理解病毒侵染与宿主天然免疫应答的相互调控与病毒逃逸机制是开发新型、高效抗感染药物的重要基础。我们通过质谱分析等技术鉴定到病毒感染的巨噬细胞中，Raf激酶抑制蛋白RKIP/PEBP1的109位丝氨酸发生去磷酸化。初步实验显示RKIP促进VSV病毒诱导的I型干扰素的产生从而抑制病毒的复制，而RKIP S109A（Ser突变成Ala模拟去磷酸化）则失去上述功能。提示RKIP及其109位丝氨酸的磷酸化在抗病毒固有免疫中发挥重要的作用。本项目将利用RKIP敲除小鼠、基因转染、RNA沉默等技术明确RKIP及RKIP109 磷酸化对抗病毒固有免疫反应中的调控作用及分子机制，同时探讨病毒调控RKIP S109磷酸化/去磷酸化的作用机制和生理、病理意义。本项目地完成可进一步丰富RKIP分子的生理功能，并提出新的抗病毒调控分子/调控位点，为寻找抗病毒感染分子靶标提供理论依据。

Understanding the interaction of virus invading and the host innate immune response and the mechanism underlined the virus escaping host innate antivirus immunity is very important to explore the novel anti-infection medicine. We had identified VSV induced the Raf kinase inhibitor RKIP/PEBP1 dephosphorylation at Ser 109 in peritoneal macrophage by phosphoproteomics approach. Our preliminary research showed that RKIP promotes VSV-induced production of type I interferon and inhibits VSV replication in macrophage. RKIP S109A mutant in which 109 serine was mutated into alanine to mimic nonphosphorylation lose the anti-virus function. These results indicate RKIP and RKIP 109 phosphorylation play important role in anti-virus innate immunity, Using the RKIP knockout mice, we will further explore the role of RKIP and RKIP 109 phosphorylation in the anti-virus immune response and related molecular mechanisms. Also, we will work on the mechanisms and physiological/pathological significance involved in the phosphoryaltion /dephosphorylation of RKIP Serine 109 induced by virus infection. All these information will help to clarify the physiological and pathological function of RKIP and provide novel regulatory mechanisms for anti-viral immune response and may provide new targets for the treatment of virus infection.