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-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.
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: S Saif
authors.initials: SS
authors.lastname: Hasan
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Miller
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.|The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: Gopal
authors.initials: G
authors.lastname: Sapparapu
authors.affiliation: Department of Pathology &Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Estefania
authors.initials: E
authors.lastname: Fernandez
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Thomas
authors.identifier: 0000-0002-2150-9792
authors.initials: T
authors.lastname: Klose
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Long
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Fokine
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Porta
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.|Markey Center for Structural Biology and Purdue Institute for Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Wen
authors.identifier: 0000-0002-1292-2411
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Pathology &Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA.|Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.|Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.|Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.|The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.|Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.|Markey Center for Structural Biology and Purdue Institute for Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kuhn
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.|Markey Center for Structural Biology and Purdue Institute for Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rossmann
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology*; D000914:Antibodies, Viral / Q000737:chemistry / Q000276:immunology*; D001665:Binding Sites; D020285:Cryoelectron Microscopy; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D000072417:Protein Domains; D055503:Protein Multimerization; D015678:Viral Structural Proteins / Q000737:chemistry / Q000276:immunology*; D000071244:Zika Virus / Q000276:immunology* / Q000502:physiology / Q000648:ultrastructure; D000071243:Zika Virus Infection / Q000276:immunology* / Q000821:virology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015678:Viral Structural Proteins