I型单纯疱疹病毒皮层蛋白UL46逃逸宿主DNA识别抗病毒天然免疫信号通路分子机制的研究

Herpes simplex virus type 1 (HSV-1), an archetypal member of herpesviruses family, is widespread in the population. HSV-1 causes lifelong infection including cold sores, herpes simplex keratitis and encephalitis, and there is no effective vaccine or drug to prevent HSV-1 latent infection. HSV infection is proven to increase the risk of acquiring and transmitting human immunodeficiency virus (HIV). To date, HSV-1 remains a threat to public health. Innate immunity plays an important role in host resistance to viral infection, whereas viruses have evolved a variety of mechanisms to evade the host innate immune responses. Currently, the study of the interaction between UL46 and the host focuses on PI3K/Akt signal pathway. However, the molecular mechanisms that UL46 protein counteract the host innate antiviral immunity and its roles in HSV-1 pathogenesis are still illusive. This project aims to investigate the molecular mechanisms by which HSV-1 UL46 to subvert the DNA sensing antiviral innate immunity via dual luciferase reporter (DLR) system assays, immunoprecipitation, construction of UL46-null HSV-1 with CRISPR/Cas9 and other molecular biology and immunology techniques. We will dissect the molecular mechanisms to evade the antiviral innate immunity by UL46 and its contribution to the pathogenesis of HSV-1. This study will help identify new drug targets and develop vaccine and new antiviral approaches against HSV-1.

I型单纯疱疹病毒（HSV-1）作为人类疱疹病毒的经典代表在人群中感染比较普遍，可导致口唇疱疹、角膜结膜炎、脑炎等疾病，也是促进HIV-1流行的重要因素之一。目前尚无有效疫苗和根治潜伏感染的药物，HSV-1仍是危害人类健康的重要病原体之一。天然免疫在宿主抵抗病毒感染中发挥重要作用，然而，病毒则进化出多种机制逃逸抗病毒天然免疫。目前HSV-1皮层蛋白UL46与宿主的相互作用仅限于PI3K/Akt信号通路，而其是否逃逸宿主抗病毒天然免疫及其在HSV-1致病中的作用尚不清楚。本课题拟通过多种分子生物学、免疫学实验技术，并采用CRISPR/Cas9系统构建UL46缺失病毒和靶基因敲除细胞系，揭示HSV-1 UL46逃逸宿主DNA识别抗病毒天然免疫的分子机制，最终阐明UL46在HSV-1致病中的作用机制，为HSV-1的防治、寻找新的药物靶点以及研发新型药物和疫苗提供科学理论依据。

I型单纯疱疹病毒（HSV-1）作为人类疱疹病毒的经典代表在人群中感染比较普遍，可导致口唇疱疹、角膜结膜炎、脑炎等疾病，也是促进HIV-1流行的重要因素之一。目前尚无有效疫苗和根治潜伏感染的药物，HSV-1仍是危害人类健康的重要病原体之一。天然免疫在宿主抵抗病毒感染中发挥重要作用，然而，病毒则进化出多种机制逃逸抗病毒天然免疫。目前HSV-1皮层蛋白UL46与宿主的相互作用仅限于PI3K/Akt信号通路，而其是否逃逸宿主抗病毒天然免疫及其在HSV-1致病中的作用尚不清楚。本课题拟通过多种分子生物学、免疫学实验技术，并采用CRISPR/Cas9系统构建UL46缺失病毒和靶基因敲除细胞系，揭示HSV-1 UL46逃逸宿主DNA识别抗病毒天然免疫的分子机制，最终阐明UL46在HSV-1致病中的作用机制，为HSV-1的防治、寻找新的药物靶点以及研发新型药物和疫苗提供科学理论依据。