EV-D68病毒受体识别和入侵机制研究

Enterovirus D68 (EV-D68) is one of seriously emerging endemic viruses globally in the past decade. Thus far, the pathogenesis of EV-D68 remains to be investigated. The applicant has first reported the original research in Cell Host & Microbe that identified human intercellular adhesion molecule ICAM-5 as a functional entry receptor for EV-D68. However, the precise mechanism of the interaction between EV-D68 and virus receptor is still unclear. Our preliminary experiments have demonstrated that another intercellular adhesion molecule ICAM-3 could also increase the sensitivity of non-permissive cells to EV-D68 infection. Based on the experiences gained from previous studies on the identification of EV-D68 receptor ICAM-5 and our preliminary data, the proposed project could be divided into four sections: 1) investigate the effects of the novel virus receptor ICAM-3 on EV-D68 enter into host cells, 2) assess the determinant of the expression of virus receptor on the cell tropism of EV-D68, 3) analyze the molecular interaction between virus and receptors, and 4) study the regulation of virus receptors ICAM-3 or ICAM-5 by glycosylation modification. These studies will extend our understanding on the mechanism of infection and entry of EV-D68, which would be informative for the rational design of specific antiviral drug target.

肠道病毒EV-D68是近年全球暴发的重大传染病致病原之一，其致病机理至今研究甚少。申请人于2016年在国际期刊Cell Host & Microbe上首次报道了细胞间隙粘附分子ICAM-5是EV-D68病毒入侵宿主细胞的受体。但是，EV-D68病毒与受体之间相互作用的分子机制仍不明确。申请人前期预实验已发现细胞间隙粘附分子家族中另一个蛋白ICAM-3同样可以促进EV-D68病毒入侵非允许细胞。基于申请人在EV-D68病毒受体鉴定中的研究经验和前期数据结果，本项目拟从EV-D68病毒新受体ICAM-3蛋白的功能鉴定、病毒受体的表达谱对EV-D68病毒亲嗜性的影响、病毒与受体的分子作用机制以及糖基化修饰对病毒受体功能的调控作用四个方向进一步拓展国际领域对EV-D68病毒感染与入侵机制的认识，对合理设计具有针对性的抗病毒药物作用靶点具有重要的指导意义。

本项目基于申请人在EV-D68病毒受体鉴定中的研究经验和前期数据结果，本项目从EV-D68病毒新受体ICAM-3蛋白的功能鉴定、病毒受体的表达谱对EV-D68病毒亲嗜性的影响、病毒与受体的分子作用机制以及糖基化修饰对病毒受体功能的调控作用四个方向，证实细胞间隙粘附分子ICAM-3是一个新EV-D68病毒入侵受体，进一步拓展国际领域对EV-D68病毒感染与入侵机制的认识，对合理设计具有针对性的抗病毒药物作用靶点具有重要的指导意义。