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

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TitleA human antibody against Zika virus crosslinks the E protein to prevent infection.
Publication TypeJournal Article
Year of Publication2017
AuthorsS Hasan, S, Miller, A, Sapparapu, G, Fernandez, E, Klose, T, Long, F, Fokine, A, Porta, JC, Jiang, W, Diamond, MS, Crowe, JE, Kuhn, RJ, Rossmann, MG
JournalNat Commun
Volume8
Pagination14722
Date Published2017 03 16
ISSN2041-1723
KeywordsAntibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Binding Sites, Cryoelectron Microscopy, HEK293 Cells, Humans, Models, Molecular, Protein Binding, Protein Domains, Protein Multimerization, Viral Structural Proteins, Zika Virus, Zika Virus Infection
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.

DOI10.1038/ncomms14722
Alternate JournalNat Commun
PubMed ID28300075
PubMed Central IDPMC5356071
Grant ListHHSN272201400024C / AI / NIAID NIH HHS / United States
R01 AI073755 / AI / NIAID NIH HHS / United States
R01 AI076331 / AI / NIAID NIH HHS / United States
R01 AI104972 / AI / NIAID NIH HHS / United States
R01 AI127828 / AI / NIAID NIH HHS / United States