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

S. Saif Hasan, Andrew Miller, Gopal Sapparapu, Estefania Fernandez, Thomas Klose, Feng Long, Andrei Fokine, Jason C. Porta, Wen Jiang, Michael S. Diamond, James E. Crowe, Richard J. Kuhn, Michael G. Rossmann

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Abstract

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.

Original languageEnglish
Article number14722
JournalNature communications
Volume8
DOIs
StatePublished - Mar 16 2017

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    Hasan, S. S., Miller, A., Sapparapu, G., Fernandez, E., Klose, T., Long, F., Fokine, A., Porta, J. C., Jiang, W., Diamond, M. S., Crowe, J. E., Kuhn, R. J., & Rossmann, M. G. (2017). A human antibody against Zika virus crosslinks the E protein to prevent infection. Nature communications, 8, [14722]. https://doi.org/10.1038/ncomms14722