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

Author

Listed:
  • S. Saif Hasan

    (Purdue University)

  • Andrew Miller

    (Purdue University)

  • Gopal Sapparapu

    (Vanderbilt University Medical Center
    The Vanderbilt Vaccine Center, 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
    Markey Center for Structural Biology and Purdue Institute for Inflammation, Immunology and Infectious Disease, Purdue University)

  • Michael S. Diamond

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine
    Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine)

  • James E. Crowe Jr.

    (Vanderbilt University Medical Center
    The Vanderbilt Vaccine Center, Vanderbilt University Medical Center
    Microbiology and Immunology, Vanderbilt University)

  • Richard J. Kuhn

    (Purdue University
    Markey Center for Structural Biology and Purdue Institute for Inflammation, Immunology and Infectious Disease, Purdue University)

  • Michael G. Rossmann

    (Purdue University
    Markey Center for Structural Biology and Purdue Institute for Inflammation, Immunology and Infectious Disease, Purdue University)

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.

Suggested Citation

  • 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 Jr. & Richard J. Kuh, 2017. "A human antibody against Zika virus crosslinks the E protein to prevent infection," Nature Communications, Nature, vol. 8(1), pages 1-6, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14722
    DOI: 10.1038/ncomms14722
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