埃博拉病毒入侵宿主细胞的分子机制

 埃博拉病毒是一类能够感染并引起人和灵长类动物发生埃博拉出血热的烈性囊膜病毒。发现近40年中，埃博拉病毒给人类生命带来了极大威胁。然而，目前人们对于埃博拉病毒的了解非常有限，尤其是病毒与其宿主细胞受体的结合机制和膜融合机制相关信息的缺失，使得针对埃博拉病毒的特效药物的设计和研发工作阻碍重重。本文综述了埃博拉病毒分类、形态、病毒蛋白和病毒生命周期，着重介绍了高福院士团队在埃博拉病毒入侵宿主细胞的分子机制研究中的成果。通过结构学手段解析了埃博拉病毒激活态囊膜糖蛋白GPcl与宿主细胞受体NPC1分子的复合物结构，从原子水平上阐明了埃博拉病毒与宿主细胞相互识别的机制，并在结构基础上对病毒的膜融合促发机制做出推测，提出以埃博拉病毒为代表的新的（第5种）囊膜病毒膜融合激发机制，为抗埃博拉病毒药物和疫苗的设计提供了结构基础。

The molecular basis of Ebola virus entry into host cells

Belonging to Filoviridae family, Ebola virus is a type of enveloped virus that can cause Ebola hemorrhagic fever in humans and primates. Because of its high mortality rate, Ebola virus now is listed as the most virulent pathogens by the World Health Organization. Since it was first found in 1976, Ebola virus has killed tens of thousands of people in Africa, brought great threat to human life and caused enormous economic losses. Therefore, prevention and control of Ebola virus have always been an important part of scientific researches. However, the understanding of Ebola virus is very limited especially in the cell surface receptors and the membrane fusion mechanism, which has hindered antiviral drug design and development. In this paper, we summarize Ebola virus in terms of taxonomy, morphology, viral proteins and viral life cycle, and highlight the achievements made by George Fu Gao's group in the study of molecular basis of Ebola virus entry into host cells. They include the determination of the crystal structures of NPC1-C and its complex with GPcl, which clarifies the recognition mechanism of Ebola virus and its host cell receptor at atomic level. Furthermore, their results reveal the molecular basis of GPcl/NPC1 interactions, thereby shedding light on the mechanism of Ebola virus membrane fusion, which will guide further development of small antiviral molecules and peptides for prevention and/or treatment of Ebola virus infection.