I型单纯疱疹病毒皮层蛋白UL24逃逸宿主抗病毒天然免疫分子机制的研究

Herpes simplex virus type 1 (HSV-1), the 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. HSV-1 UL24 protein is conserved across the herpesvirus family and has been reported to be a virulence determinant in murine and guinea pig disease models. However, the molecular mechanisms that UL24 protein and its homologues 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 UL24 to subvert the innate antiviral immunity and other important signal pathways, via dual luciferase reporter (DLR) system assays, co-immunoprecipitation, construction of UL24-null HSV-1 and other molecular biology and immunology techniques. We will dissect the molecular mechanisms of UL24 and its conserved homologues mediated immune evasion and their contribution to pathogenesis. This study will help identify new drug targets and develop vaccine and new antiviral approaches against herpesviruses.

人类疱疹病毒的经典代表Ⅰ型单纯疱疹病毒（HSV-1）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。由于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，病毒则进化出多种机制逃逸宿主天然免疫。HSV-1皮层蛋白UL24在疱疹病毒家族中保守，是重要的毒力因子，而其逃逸宿主抗病毒天然免疫及其致病的分子机制尚不清楚。本课题拟通过多种分子生物学、免疫学实验技术，并采用细菌人工染色体技术和CRISPR/Cas9系统构建UL24缺失和突变病毒，以HSV-1 UL24为代表结合其它疱疹病毒保守同源蛋白研究UL24逃逸宿主抗病毒天然免疫的分子机制，最终揭示保守蛋白UL24在人类疱疹病毒致病中的分子机制，为疱疹病毒防治、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。

人类疱疹病毒的经典代表Ⅰ型单纯疱疹病毒（HSV-1）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。由于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，病毒则进化出多种机制逃逸宿主天然免疫。HSV-1皮层蛋白UL24在疱疹病毒家族中保守，是重要的毒力因子，而其逃逸宿主抗病毒天然免疫及其致病的分子机制尚不清楚。本课题拟通过多种分子生物学、免疫学实验技术，并采用细菌人工染色体技术和CRISPR/Cas9系统构建UL24缺失和突变病毒，以HSV-1 UL24为代表结合其它疱疹病毒保守同源蛋白研究UL24逃逸宿主抗病毒天然免疫的分子机制，最终揭示保守蛋白UL24在人类疱疹病毒致病中的分子机制，为疱疹病毒防治、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。

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