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; Michael G. Rossmann

doi:10.1038/ncomms14722

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, Michael G. Rossmann

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114 Scopus citations

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.

Original language	English
Article number	14722
Journal	Nature communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms14722
State	Published - Mar 16 2017

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title = "A human antibody against Zika virus crosslinks the E protein to prevent 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-Barr{\'e} syndrome in adults. Neutralizing antibodies present a possible therapeutic approach to prevent and control ZIKV infection. Here we present a 6.2 {\AA} 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.",

author = "Hasan, {S. Saif} and Andrew Miller and Gopal Sapparapu and Estefania Fernandez and Thomas Klose and Feng Long and Andrei Fokine and Porta, {Jason C.} and Wen Jiang and Diamond, {Michael S.} and Crowe, {James E.} and Kuhn, {Richard J.} and Rossmann, {Michael G.}",

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doi = "10.1038/ncomms14722",

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T1 - A human antibody against Zika virus crosslinks the E protein to prevent infection

AU - Hasan, S. Saif

AU - Miller, Andrew

AU - Sapparapu, Gopal

AU - Fernandez, Estefania

AU - Klose, Thomas

AU - Long, Feng

AU - Fokine, Andrei

AU - Porta, Jason C.

AU - Jiang, Wen

AU - Diamond, Michael S.

AU - Crowe, James E.

AU - Kuhn, Richard J.

AU - Rossmann, Michael G.

PY - 2017/3/16

Y1 - 2017/3/16

N2 - 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.

AB - 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.

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DO - 10.1038/ncomms14722

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SN - 2041-1723

VL - 8

JO - Nature communications

JF - Nature communications

M1 - 14722

ER -

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

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