肠道病毒B家族埃可病毒16(E16)型病毒样颗粒的结构解析

Structure of The Virus-like Particle of Echovirus 16 Implies a Universal Vaccine Design Against Enterovirus B

肠道病毒B家族是引发人类病毒性脑炎和脑膜炎的重要病原体之一.然而目前市场上尚缺乏针对此类病毒的特异性疫苗.病毒样颗粒具有保留病毒真实结构特点、不含病毒核酸、不具备病毒复制与感染能力的特征,为开发有效、稳定且安全的新型疫苗提供了理想方案,特别是针对无囊膜的肠道病毒.本研究中,基于昆虫细胞表达系统,经密度梯度离心等方法获得埃可病毒16(E16)型的病毒样颗粒(virus-like particle;VLP).借助冷冻电镜单颗粒技术,成功将该病毒VLP解析到原子分辨率(2.8?),结构分析显示:与同源病毒E30的结构相类似,E16-VLP具备肠道病毒所特有的能够引起机体产生特异性中和免疫反应的重要结构特征,具有较大的疫苗开发价值.本实验室建立的方法在抗肠道病毒B家族通用疫苗的设计与开发上具有巨大潜力.

Echovirus B serves as one of the important causative agents of viral meningitis and encephalitis all over the world,but no specific vaccines against this virus family are thus far available in the market.Structurally similar to the natural virus whilst lacking the nucleic acid essential for viral replication and infectivity,the viruslike particle(VLP),has widely been considered an ideal vaccine candidate of next generation,especially for the enterovirus that has no envelope.In this study,we designed a platform based on the insect expression system which succeeded in producing the VLP of E16.Then,the 2.8-?cryo-EM structure of E16-VLP was determined and characterized.In line with the overall structure of E30,another member of enterovirus B,E16-VLP employed the well-studied structural features found in the outer surface of most enterovirus members and have been regarded to be the regions able to induce specific neutralizing antibodies,indicative of its potential value of vaccine development.Altogether,our established platform could serve as an important candidate to produce a safe and universal vaccine against enterovirus B.