泛素化是一种广泛存在的蛋白翻译后修饰，参与诸多重要生命过程，包括蛋白质降解、信号传导和免疫反应等。多种病毒编码去泛素化酶（DUB），可通过调控宿主蛋白的泛素化来干扰宿主抗病毒应答。人类疱疹病毒的典型代表Ⅰ型单纯疱疹病毒(HSV-1)在人群中极为常见，可导致口唇疱疹、角膜结膜炎、脑炎等疾病。HSV-1皮层蛋白UL36及其它人类疱疹病毒同源蛋白氨基端具有DUB活性，然而目前对其干扰宿主抗病毒天然免疫及其它重要信号通路的机制尚不清楚。本课题拟通过荧光素酶双报告基因检测系统结合多种分子生物学、免疫学实验技术以及采用细菌人工染色体技术构建基因缺失或突变病毒，以HSV-1 UL36为代表结合其它同源蛋白探讨人类疱疹病毒DUB干扰宿主天然免疫等重要信号通路的分子机制，最终阐明UL36等同源蛋白的DUB在人类疱疹病毒致病机制中的作用，为防治疱疹病毒寻找新的药物靶点以及研发新型药物和疫苗奠定理论基础。

Ubiquitylation is a broad post-translational protein modification, which has been suggested to be one of the most important regulatory mechanisms in various biological processes, including protein degradation, signal transduction and immune responses, etc. Many viruses encode deubiquitinase (DUB) to subvert the host immune response by manipulating the ubiquitylation. Herpes simplex virus type-1 (HSV-1), the archetypal member of herpesviruses family, is widespread in the population. Infection of HSV-1 causes cold sores, keratoconjunctivitis and encephalitis, etc. The N-terminus of HSV-1 largest tegument protein UL36 and its homologues in other human herpsviruses display remarkable DUB activity, also named UL36USP (UL36 ubiquitin-specific protease). However, the host innate antiviral immunity and other crucial biological processes affected by UL36 and its homologues are still illusive. This project aims to investigate the molecular mechanisms by which UL36USP and its homologues to counteract the innate antiviral immunity and other main signal pathways, via dual luciferase reporter (DLR) system assays, co-immunoprecipitation (Co-IP), construction of UL36-mutant HSV-1 and other molecular biology and immunology techniques. The study will clarify the molecular mechanisms of herpesviral pathogenesis, and pave the way to find new drug targets and develop vaccine and new antiviral approaches against herpesviruses.