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 () and Michael G. Rossmann ()
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S. Saif Hasan: Purdue University
Andrew Miller: Purdue University
Gopal Sapparapu: Vanderbilt University Medical Center
Estefania Fernandez: Washington University School of Medicine
Thomas Klose: Purdue University
Feng Long: Purdue University
Andrei Fokine: Purdue University
Jason C. Porta: Purdue University
Wen Jiang: Purdue University
Michael S. Diamond: Washington University School of Medicine
James E. Crowe: Vanderbilt University Medical Center
Richard J. Kuhn: Purdue University
Michael G. Rossmann: Purdue University

Nature Communications, 2017, vol. 8, issue 1, 1-6

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14722

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