Viperin是干扰素(Interferon,IFN)诱导产生的重要抗病毒蛋白，具备强大而广谱的抗DNA和RNA病毒的效应。申请人前期发表的工作表明Viperin蛋白受到UBE4A介导的泛素化修饰。蛋白泛素化和去泛素化修饰精细调控着蛋白水平，因此在疾病相关的信号通路中扮演着重要角色。然而，Viperin蛋白的去泛素化调控机制仍未阐明。申请人通过去泛素化酶文库的筛选，发现USP33是Viperin潜在的去泛素化酶。因此，本项目拟应用遗传学、生物化学、细胞生物学等手段，深入分析USP33与Viperin蛋白的相互作用，以及USP33对Viperin泛素化和蛋白水平的调控。进一步，申请人拟探讨USP33对IFN抗病毒活性的影响，并利用USP33-/-小鼠分析USP33对宿主抗病毒功能的调控。本项目通过探索抗病毒蛋白Viperin的去泛素化调控机制，旨在为临床抗病毒治疗提供潜在的分子靶标。

Viperin is an important antiviral protein induced by interferon (IFN). It has strong and broad-spectrum effects to fight against DNA and RNA viruses. Previous work published by the applicant indicated that Viperin protein can be ubiquitinated by UBE4A. Protein ubiquitination and de-ubiquitination play a key role in disease-related signaling pathways. However, the mechanism of Viperin de-ubiquitination has not been elucidated. By screening a deubiquitinase expression library, the applicant found that USP33 could be a potential deubiquitinase of Viperin. Therefore, this project plans to use genetics, biochemistry, cell biology and other means to deeply analyze the interaction between USP33 and Viperin protein, as well as the regulation of USP33 on Viperin ubiquitination and protein level. Further, the applicant intends to explore the effect of USP33 on the antiviral activity of IFN, and analyze the regulation of USP33 on host antiviral function using USP33 knockout mice. This project focuses on studying the deubiquitinase-mediated regulation of antiviral Viperin protein, aiming to provide potential therapeutic targets for clinical antiviral therapy.