James Crowe
Faculty Member
Last active: 3/31/2020

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

Hasan SS, Miller A, Sapparapu G, Fernandez E, Klose T, Long F, Fokine A, Porta JC, Jiang W, Diamond MS, Crowe JE, Kuhn RJ, Rossmann MG
Nat Commun. 2017 8: 14722

PMID: 28300075 · PMCID: PMC5356071 · 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.

MeSH Terms (14)

Antibodies, 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

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