干扰素（IFNs）是固有免疫的重要组成部分以及机体抵御病毒感染第一道防线中最重要的细胞因子。在调控IFNs抗病毒信号的各类分子中，腺苷脱氨酶（ADAR1）近年来被发现能抑制IFNs介导的抗病毒功能。然而，有关IFNs信号如何克服ADAR1的负性调控作用从而发挥有效抗病毒功能仍有待研究。我们前期工作发现ADAR1敲降后IFNα抗VSV病毒作用显著增强，并且发现IFNα能诱导ADAR1蛋白水平下降和泛素化水平增加，预研结果提示参与ADAR1泛素化的E3连接酶很可能是Beta-Trcp。因此，本项目拟探讨IFNα诱导负调控因子ADAR1泛素化和降解的信号机制，明确调控ADAR1泛素化的E3连接酶，并进一步探讨该E3与ADAR1相互作用及其对IFNα抗病毒功能的影响。通过探索IFNα抗病毒信号中抑制性分子的泛素化调控，有助于人们理解IFNα抗病毒信号的新机制，并为临床抗病毒治疗提供潜在的新靶点。

The interferons act as an important component in innate immunity, which are also the most important cytokines in the first line of defense against virus infection. Among various molecules involved in the regulation of IFNs antiviral signaling, the adenosine deaminase acting on RNA1 (ADAR1) has recently been found to inhibit the IFNs-mediated antiviral function. However, it remains to be explored that how did the IFNs signaling overcome the inhibitory effect of ADAR1 and finally play an effective role in antiviral function. Our preliminary data revealed that the antiviral effect of IFNα against VSV was significantly enhanced after ADAR1 knockdown, and IFNα could induce ADAR1 protein expression level decline and increase its ubiquitination level. Our preliminary data also implied that the E3 ligase Beta-Trcp is probably involved in the ubiquitination event of ADAR1. Thus, this project intends to explore the signaling mechanism of a negative regulatory factor ADAR1 whose ubiquitination and degradation was induced by IFNα, identify the potential ubiquitin E3 ligase, and finally investigate how ADAR1 interacts with its E3 ligase and its effects on IFNα antiviral function. Investigating the ubiquitin regulations of inhibitory molecules in IFNα signaling pathway would help to understand the new mechanism of IFNα antiviral signaling and provide a potential new target for clinical antiviral therapy.