A human antibody against Zika virus crosslinks the E protein to prevent infection

作者：Hasan S Saif; Miller Andrew; Sapparapu Gopal; Fernandez Estefania; Klose Thomas; Long Feng; Fokine Andrei; Porta Jason C; Jiang Wen; Diamond Michael S; Crowe James E Jr; Kuhn Richard J^*; Rossmann Michael G^*

来源：Nature Communications, 2017, 8(1): 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-Barre syndrome in adults. Neutralizing antibodies present a possible therapeutic approach to prevent and control ZIKV infection. Here we present a 6.2 angstrom 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.

• 出版日期2017-3-16