I型单纯疱疹病毒（HSV-1）在人群中的感染极为普遍，可引起多种疾病，已成为严重危害人类健康的重要病原之一，目前尚无有效的药物和疫苗。天然免疫是宿主抵抗病毒入侵的第一道防线，其中核因子κB（NF-κB）在抗HSV-1感染中扮演着重要的角色。研究发现，HSV-1可以编码一些蛋白通过不同方式抑制NF-κB活性来调控宿主的天然免疫，然而，是否存在其它HSV-1蛋白也参与这个过程尚不明确。我们的预实验结果表明，HSV-1 UL2蛋白能明显抑制TNF-α诱导的NF-κB启动子活性，并且它是在p65水平发挥抑制作用，说明UL2是NF-κB通路新的拮抗剂。因此，本项目拟采用双荧光素酶报告系统结合多种分子生物学、免疫学和病毒学实验在病毒感染的细胞和动物水平深入阐明UL2抑制NF-κB信号通路的分子机制，这不仅有助于加深我们对HSV-1致病机制的认识，也可为进一步的抗病毒药物靶点设计和疫苗研制提供理论依据。

Herpes simplex virus 1 (HSV-1), a prevalent human virus that can lead to a variety of diseases, has become one of the vital pathogens that is severely harmful to human health, yet no efficient drug or vaccine has been developed. Innate immunity is the first line of host defense against viral invasion, and nuclear factor κB (NF-κB) plays a very important role in anti-HSV-1 infection. It is shown that HSV-1 can encode some proteins to control the host innate immunity by inhibiting the NF-κB activity in different ways, however, whether there are other HSV-1 proteins also participate in this process remains unknown. Our preliminary data demonstrate that UL2 can effectively inhibit the tumor necrosis factor-α (TNF-α)-mediated NF-κB promoter activity, and this inhibition takes place at the p65 level, suggesting that UL2 can serve as a new antagonist of NF-κB signaling pathway. Accordingly, this study is intended to further deeply analyse the molecular mechanism of UL2 inhibiting the NF-κB signaling pathway in the viral infected cells and animal models by utilizing dual luciferase reporter system, as well as a number of molecular biology, immunology and virology techniques. In conclusion, these works will not only assist us to understand the pathogenesis of HSV-1, but also offer a theoretical foundation for the further design of new antiviral drug target and development of efficient vaccine against HSV-1.