基于天然免疫cGAS/STING/IFN-Ⅰ信号通路研究中药复方洁泽1号“扶正祛邪”抗HSV-2作用机制

HSV-2病毒感染不仅是全球高发的性传播感染之一，严重危害人类身心健康。目前全球尚无HSV-2疫苗用于临床，且治疗药物耐药报道越来越多。IFN-I是重要抗病毒因子，新近研究表明cGAS/STING通路活化后主要产生IFN-I介导抗病毒天然免疫应答，而HSV-2利用自身多种病毒蛋白拮抗这一免疫应答。前期研究发现洁泽1号显著增加IFN-Ⅰ的产生，具有良好的抗HSV-2作用。结合病毒与宿主免疫的博弈和中医“正邪相争”理论内在联系，本项目提出假说：洁泽1号可能通过激活并上调cGAS/STING信号通路促进IFN-I产生发挥抗HSV-2作用，通过“扶正”达到“祛邪”目的。本研究拟构建HSV-2感染细胞和小鼠模型，应用分子生物学、分子免疫学等技术，探讨洁泽1号对cGAS/STING/IFN-Ⅰ通路的调节作用及调控靶点，以期阐明洁泽1号“扶正祛邪”抗病毒的科学内涵，为抗病毒药物研发提供新的思路。

Herpes simplex virus type 2 (HSV-2) infection has been one of the most common and highest incidence of sexually transmitted infections (STIs) worldwide. It has also been an important risk factor for the HIV transmission and brings great harm to human physical and mental health. However, there is currently no HSV-2 vaccine approved for clinical use in the world and the admitted drugs for HSV-2 treatment is being reported drug resistance with increasing frequency. The production of type Ⅰ interferon (IFN-I) mediated by cGAS-STING signaling pathway Herpes simplex virus type 2 (HSV-2) infection has been one of the most common and highest incidence of sexually transmitted infections (STIs) worldwide. It brings great harm to human physical and mental health. However, there is currently no HSV-2 vaccine approved for clinical use in the world and the admitted drugs for HSV-2 treatment is being reported drug resistance with increasing frequency. Type Ⅰ interferon is an important antiviral factor, recent studies have shown that the production of IFN-I mediated by cGAS-STING signaling pathway plays an important role in the antiviral innate immune response, whereas HSV-2 could escape or antagonize this immune response by utilizing own various virus proteins. Our previous study found that Jieze-1 could significantly increase the production of IFN-I and had a potent anti-HSV-2 effect. Therefore, we hypothesized that Jieze-1 may exert anti-HSV-2 efficiency by activating and up-regulating cGAS/STING signal pathway to promote the production of IFN-I. In this study, we intend to establish HSV-2 infected cells and mice models, and the regulatory effect and targets of Jiize-1 on cGAS/STING/IFN-I signal pathway were explored by applicating techniques of moleular biology, molecular immunology, in order to clarify the antiviral molecular mechanism of "strengthening the body resistance to eliminate pathogenic factors" of Jieze-1, and provide new ideas for the research and development of antiviral drugs.