去乙酰化酶Sirt1在I型单纯疱疹病毒感染过程中的功能和机制研究

HSV-1是一种常见且具有高度传染性的DNA病毒，乙酰化修饰在IFI16介导的抗HSV-1感染的过程中具有调控功能。去乙酰化酶Sirt1在HSV-1感染过程中的功能尚不清楚。我们的研究初步提示1）Sirt1和IFI16相互作用2）Sirt1抑制IFI16的乙酰化修饰3）抑制Sirt1的表达或活性均能促进HSV-1诱导的固有免疫应答反应。据此我们提出假说，Sirt1通过对IFI16去乙酰化来调控抗HSV-1的固有免疫应答反应。我们拟通过免疫印迹、实时定量PCR、ELISA、免疫共沉淀、免疫荧光、荧光素酶报告基因检测、空斑检测、质谱分析及RNAi等实验方法，并利用IFI16缺陷细胞、Sirt1缺陷细胞和Sirt1缺陷小鼠验证这一假说，揭示Sirt1在抗HSV-1的固有免疫应答反应中的功能及具体机制。该研究有助于深入理解机体内的抗病毒免疫应答反应，并可能为临床上病毒相关疾病的防治提供线索。

HSV-1 is a ubiquitous and highly contagious DNA virus. Acetylation plays a role in IFI16-mediated anti-viral responses. Sirt1 is a type of deacetylase and its role in HSV-1 infection is unknown. Our research suggested that Sirt1 could interact with IFI16 and might inhibit the acetylation of IFI16. The inhibition of the expression or activity of Sirt1 increased the innate immune responses triggered by HSV-1 infection. We propose the hypothesis that Sirt1 regulates the innate immune responses against HSV-1 infection by targeting IFI16 for deacetylation. We will prove this hypothesis by the methods of western blot, real-time PCR, ELISA, coimmunoprecipitation, immunofluorescence microscopy，luciferase assay, plague assay，mass spectrum and RNAi. Furthermore, we will use IFI16-KO cells, Sirt1-KO cells and Sirt1-KO mice, to illuminate the function and mechanism of Sirt1 in the innate immune responses against HSV-1 infection. This research will contribute to our understanding of host anti-viral immune responses and may provide clues for the prevention and treatment of virus-related diseases.