一种针对寨卡病毒的人源抗体可交联 E 蛋白以预防感染。
A human antibody against Zika virus crosslinks the E protein to prevent infection.
机构信息
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
出版信息
Nat Commun. 2017 Mar 16;8:14722. doi: 10.1038/ncomms14722.
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.
最近的寨卡病毒(ZIKV)疫情与不寻常和严重的临床表现有关,包括感染孕妇胎儿的小头畸形和成人的吉兰-巴雷综合征。中和抗体是预防和控制 ZIKV 感染的一种可能的治疗方法。在这里,我们展示了一个分辨率为 6.2 Å 的三维冷冻电镜(cryoEM)结构,该结构是感染性 ZIKV(株 H/PF/2013,法属波利尼西亚)与一种高度治疗性和中和性人源单克隆抗体 ZIKV-117 的 Fab 片段的复合物。该抗体已被证明可预防小鼠的胎儿感染和死亡。该结构表明,ZIKV-117 Fab 交联表面 E 糖蛋白二聚体中的单体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性三聚体。