疱疹病毒γ亚科EB病毒核释放复合体的结构与功能研究

Herpesviruses are double-stranded DNA viruses which cause many diseases in humans and animals. More than 90% of adults have been infected with at least one herpesvirus. Herpesvirus can cause oral and genital herpes and even severe encephalitis and cancer. After completing the assembly of virus capsid in the nucleus, the process will be a special secondary envelopment to complete the process of virus maturation. The nuclear egress complex (NEC) plays a very important role in the release process of nucleocapsid from the nucleus. NEC is a complex formed by two proteins that interact with the viral nucleocapsid and mediate the primary envelopment of the nucleocapsid into the nucleoplasm of the bilayer nuclear membrane. After that, the nucleocapsid is released into the cytoplasm by the process of membrane fusion with the outer nuclear membrane to complete the de-envelopment, thereby completing the nuclear egress process of the nucleocapsid from the nucleus to the cytoplasm. At present, the structural studies of nuclear egress complex of herpesviruses mainly focus on α and β subfamilies, and the structure of the nuclear egress complex of γ subfamily has not been reported yet. In this study, Epstein-Barr virus (EBV) was used to study the structure and function of nuclear egress complex from γ herpesviruses. Solving the structure of nuclear egress complex of EBV will not only reveal the molecular mechanisms of nuclear egress of herpesvirus capsid, but will also provide scientific basis for the development of virus inhibitors targeting nuclear egress complex.

疱疹病毒属于双链DNA病毒，可引起人类和动物的多种疾病，超过90%的成人曾被至少一种疱疹病毒感染过，严重的可引发脑炎和癌症等疾病。疱疹病毒衣壳在细胞核内完成组装后，会经过特殊的二次囊膜化，完成病毒成熟过程。其中核释放复合体在核衣壳的核释放过程中具有非常重要的作用。核释放复合体是由两个蛋白形成的复合体，其与病毒核衣壳相互作用，介导核衣壳在细胞核内膜处发生初级囊膜化，进入双层核膜的核周质，然后通过与细胞核膜外膜的溶膜过程将核衣壳释放入细胞质完成去囊膜化，从而完成病毒核衣壳从细胞核进入细胞质的核释放过程。目前对于疱疹病毒核释放复合体的结构研究主要集中在α和β亚科，而对于γ亚科的疱疹病毒，其结构还未有报道。本研究以γ疱疹病毒中可引起癌症的EB病毒作为研究对象，对其核释放复合体进行结构研究，并通过生化实验揭示其介导病毒核衣壳出核的分子机制，同时为研发针对核释放复合体的抗病毒抑制剂提供结构基础。

疱疹病毒属于双链DNA病毒，可引起人类和动物的多种疾病，超过90%的成人曾被至少一种疱疹病毒感染过，严重的可引发脑炎和癌症等疾病。疱疹病毒衣壳在细胞核内完成组装后，会经过特殊的二次囊膜化，完成病毒成熟过程。其中核释放复合体在核衣壳的核释放过程中具有非常重要的作用。核释放复合体是由两个蛋白形成的复合体，其与病毒核衣壳相互作用，介导核衣壳在细胞核内膜处发生初级囊膜化，进入双层核膜的核周质，然后通过与细胞核膜外膜的溶膜过程将核衣壳释放入细胞质完成去囊膜化，从而完成病毒核衣壳从细胞核进入细胞质的核释放过程。本项目以γ疱疹病毒中可引起癌症的EB病毒作为研究对象，展开对其核释放复合体的结构生物学研究，经过表达筛选纯化获得高质量复合体蛋白并获得低分辨率的蛋白晶体。本项目同时也开展了针对新冠病毒中和机制以及肠道病毒入侵机制的研究工作，本项目的成果将为抗病毒的药物及疫苗研发提供理论支持。