title: Molecular Basis for Antibody-Mediated Neutralization of New World Hemorrhagic Fever Mammarenaviruses.
abstract: In the Western hemisphere, at least five mammarenaviruses cause human viral hemorrhagic fevers with high case fatality rates. Junín virus (JUNV) is the only hemorrhagic fever virus for which transfusion of survivor immune plasma that contains neutralizing antibodies ("passive immunity") is an established treatment. Here, we report the structure of the JUNV surface glycoprotein receptor-binding subunit (GP1) bound to a neutralizing monoclonal antibody. The antibody engages the GP1 site that binds transferrin receptor 1 (TfR1)-the host cell surface receptor for all New World hemorrhagic fever mammarenaviruses-and mimics an important receptor contact. We show that survivor immune plasma contains antibodies that bind the same epitope. We propose that viral receptor-binding site accessibility explains the success of passive immunity against JUNV and that this functionally conserved epitope is a potential target for therapeutics and vaccines to limit infection by all New World hemorrhagic fever mammarenaviruses.
authors.affiliation: Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Selma
authors.initials: S
authors.lastname: Mahmutovic
authors.affiliation: Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lars
authors.initials: L
authors.lastname: Clark
authors.affiliation: Instituto Nacional de Enfermedades Virales Humanas "Dr. Julio I Maiztegui," Monteagudo 2510, Pergamino, Buenos Aires 2700, Argentina.
authors.forename: Silvana C
authors.initials: SC
authors.lastname: Levis
authors.affiliation: Instituto Nacional de Enfermedades Virales Humanas "Dr. Julio I Maiztegui," Monteagudo 2510, Pergamino, Buenos Aires 2700, Argentina.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Briggiler
authors.affiliation: Instituto Nacional de Enfermedades Virales Humanas "Dr. Julio I Maiztegui," Monteagudo 2510, Pergamino, Buenos Aires 2700, Argentina.
authors.forename: Delia A
authors.initials: DA
authors.lastname: Enria
authors.affiliation: Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harrison
authors.affiliation: Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: abraham@crystal.harvard.edu.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Abraham
mesh_terms: D057134:Antibodies, Neutralizing / Q000737:chemistry* / Q000276:immunology; D000914:Antibodies, Viral / Q000737:chemistry* / Q000276:immunology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D018051:Junin virus / Q000737:chemistry* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000276:immunology; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D008562:Membrane Glycoproteins