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

Nat Commun. 2017 Mar 16:8:14722. doi: 10.1038/ncomms14722.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / chemistry
  • Antibodies, Viral / immunology*
  • Binding Sites
  • Cryoelectron Microscopy
  • HEK293 Cells
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Domains
  • Protein Multimerization
  • Viral Structural Proteins / chemistry
  • Viral Structural Proteins / immunology*
  • Zika Virus / immunology*
  • Zika Virus / physiology
  • Zika Virus / ultrastructure
  • Zika Virus Infection / immunology*
  • Zika Virus Infection / virology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Viral Structural Proteins