Atomic structures of enterovirus D68 in complex with two monoclonal antibodies define distinct mechanisms of viral neutralization

11月5日，《自然》子刊《自然•微生物学》（Nature Microbiology）在线刊出了我校夏宁邵教授团队发表的题为“Atomic Structures of Enterovirus D68 in Complex with Two Monoclonal Antibodies Define Distinct Mechanisms of Viral Neutralization”的研究论文。这是夏宁邵教授团队在《自然•通讯》（Nature Communications，2017）、《科学•进展》（Science Advances，2018）上发表手足口病重要病原体CVA6、CVA10研究论文之后的又一项关于肠道病毒的重要研究成果。该研究通过解析肠道病毒D组68型（EV-D68）不同类型病毒颗粒及其免疫复合物的高分辨率结构，系统阐明了EV-D68病毒的生活周期及各时期的病毒中和机制，进一步完善了小RNA病毒的吸附入胞及感染机制理论，为EV-D68新型疫苗、抗病毒治疗药物的研发提供重要的理论指导。该研究依托电镜技术平台，解析了EV-D68病毒生活周期中的三种代表性颗粒成熟颗粒、脱衣壳中间态和前体病毒衣壳的近原子分辨率结构，阐明了三种病毒颗粒间的结构差异，以及成熟颗粒转变为脱衣壳中间态的分子机制。夏宁邵教授、李少伟教授、程通副教授和美国国立卫生研究院（NIH）高级研究员Barney Graham博士为该论文的共同通讯作者。郑清炳工程师、博士生朱瑞、博士后徐龙发、博士生何茂洲和美国加州大学圣地亚哥分校颜晓东博士为该论文共同第一作者。【Abstract】Enterovirus D68 (EV-D68) undergoes structural transformation between mature, cell-entry intermediate (A-particle) and empty forms throughout its life cycle. Structural information for the various forms and antibody-bound capsids will facilitate the development of effective vaccines and therapeutics against EV-D68 infection, which causes childhood respiratory and paralytic diseases worldwide. Here, we report the structures of three EV-D68 capsid states representing the virus at major phases. We further describe two original monoclonal antibodies (15C5 and 11G1) with distinct structurally defined mechanisms for virus neutralization. 15C5 and 11G1 engage the capsid loci at icosahedral three-fold and five-fold axes, respectively. To block viral attachment, 15C5 binds three forms of capsids, and triggers mature virions to transform into A-particles, mimicking engagement by the functional receptor ICAM-5, whereas 11G1 exclusively recognizes the A-particle. Our data provide a structural and molecular explanation for the transition of picornavirus capsid conformations and demonstrate distinct mechanisms for antibody-mediated neutralization.This work was supported by a grant from the National Science and Technology Major Projects for Major New Drugs Innovation and Development (no. 2018ZX09711003-005-003), the National Science and Technology Major Project of Infectious Diseases (no. 2017ZX10304402-002-003), the National Natural Science Foundation of China (no. 81401669 and 81801646) and the Natural Science Foundation of Fujian Province (no. 2015J05073). This work was supported in part by funding by the National Institutes of Health (grants R37-GM33050, GM071940, DE025567 and AI094386). We acknowledge the use of instruments at the Electron Imaging Center for Nanomachines supported by UCLA and by instrumentation grants from the NIH (1S10RR23057 and 1U24GM116792) and NSF (DBI-1338135 and DMR-1548924). 该研究获得了国家自然科学基金、新药创制国家科技重大专项、传染病防治国家科技重大专项和美国国立卫生研究院基金的资助

(R)urban Synergy vs. Climate Change: The Impact of ICT Networks on the Process of Adaptation and Mitigation

The chapter provides an insight into the relationship between synergic (r)urban systems, information networks and climate change, discussing the emerging ideas, and concepts related to the increasing use of information networks in the process of climate adaptation and mitigation. Emphasizing the strategic role of both digital and material information flows, supported by ICT tools, the chapter focuses on two main domains of data exchange and knowledge transfer: the public communication of climate change and the connectivity and interaction within (r)urban hybrid systems. Underlining the issues of effectiveness, accessibility, and low-carbon outcomes of synergic (r)urban reactions to climate shift, recent environmental and technological trends are considered in accordance with the preferred spatio-functional flexibility of emerging (r)urban hybrid settlements. The chapter also identifies and analyses three areas of ICT applicability, targeting the role of information networks in the anticipated climate-friendly development: human behavior, ecological awareness, and general efficiency