A human antibody against Zika virus crosslinks the E protein to prevent infection.
A human antibody against Zika virus crosslinks the E protein to prevent infection.
复制标题
DOI：
10.1038/ncomms14722
复制
发表时间：
2017-03-16
影响因子：
16.6
通讯作者：
Rossmann MG
中科院分区：
文献类型：
--
作者：
Hasan SS;Miller A;Sapparapu G;Fernandez E;Klose T;Long F;Fokine A;Porta JC;Jiang W;Diamond MS;Crowe JE Jr;Kuhn RJ;Rossmann MG
最近的寨卡病毒（ZIKV）流行与异常和严重的临床表现有关，包括受感染孕妇胎儿的小头畸形和成人的格林-巴利综合征。中和抗体提供了预防和控制ZIKV感染的可能的治疗方法。在这里，我们呈现了与高度治疗性和中和性人单克隆抗体ZIKV-117的Fab片段复合的感染性ZIKV（菌株H/PF/2013，法属波利尼西亚）的6.2 μ m分辨率三维冷冻电子显微镜（cryoEM）结构。该抗体已被证明可以防止小鼠的胎儿感染和死亡。该结构显示ZIKV-117 Fab交联表面E糖蛋白二聚体内以及相邻二聚体之间的单体，从而防止E蛋白单体在内体的酸性环境中重组为融合三聚体。人类单克隆抗体ZIKV-117已显示出对寨卡病毒的治疗潜力，同时与其他黄病毒没有交叉反应性。在这里，作者呈现了与ZIKV-117 Fab复合的ZIKV毒株H/PF/2013的冷冻-EM结构，揭示了其中和机制。
The recent Zika virus (ZIKV) epidemic has been linked to unusual and severe clinical manifestations including microcephaly in fetuses of infected pregnant women and Guillian-Barré syndrome in adults. Neutralizing antibodies present a possible therapeutic approach to prevent and control ZIKV infection. Here we present a 6.2 Å resolution three-dimensional cryo-electron microscopy (cryoEM) structure of an infectious ZIKV (strain H/PF/2013, French Polynesia) in complex with the Fab fragment of a highly therapeutic and neutralizing human monoclonal antibody, ZIKV-117. The antibody had been shown to prevent fetal infection and demise in mice. The structure shows that ZIKV-117 Fabs cross-link the monomers within the surface E glycoprotein dimers as well as between neighbouring dimers, thus preventing the reorganization of E protein monomers into fusogenic trimers in the acidic environment of endosomes. The human monoclonal antibody ZIKV-117 has demonstrated therapeutic potential against Zika while showing no cross-reactivity to other flaviviruses. Here the authors present a cryo-EM structure of the ZIKV strain H/PF/2013 in complex with the ZIKV-117 Fab, shedding light on its neutralization mechanism.