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Convergent immunological solutions to Argentine hemorrhagic fever virus neutralization

DOI: 10.1073/pnas.1702127114 DOI Help

Authors: Antra Zeltina (Wellcome Trust Centre for Human Genetics, University of Oxford) , Stefanie A. Krumm (Guy’s Hospital, King’s College London) , Mehmet Sahin (University of Basel) , Weston B. Struwe (Oxford Glycobiology Institute, University of Oxford) , Karl Harlos (Wellcome Trust Centre for Human Genetics, University of Oxford) , Jack H. Nunberg , Max Crispin (Oxford Glycobiology Institute, University of Oxford) , Daniel D. Pinschewer (University of Basel) , Katie J. Doores (Guy’s Hospital, King’s College London) , Thomas A. Bowden (Wellcome Trust Centre for Human Genetics, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences

State: Published (Approved)
Published: June 2017
Diamond Proposal Number(s): 10627

Abstract: Transmission of hemorrhagic fever New World arenaviruses from their rodent reservoirs to human populations poses substantial public health and economic dangers. These zoonotic events are enabled by the specific interaction between the New World arenaviral attachment glycoprotein, GP1, and cell surface human transferrin receptor (hTfR1). Here, we present the structural basis for how a mouse-derived neutralizing antibody (nAb), OD01, disrupts this interaction by targeting the receptor-binding surface of the GP1 glycoprotein from Junín virus (JUNV), a hemorrhagic fever arenavirus endemic in central Argentina. Comparison of our structure with that of a previously reported nAb complex (JUNV GP1–GD01) reveals largely overlapping epitopes but highly distinct antibody-binding modes. Despite differences in GP1 recognition, we find that both antibodies present a key tyrosine residue, albeit on different chains, that inserts into a central pocket on JUNV GP1 and effectively mimics the contacts made by the host TfR1. These data provide a molecular-level description of how antibodies derived from different germline origins arrive at equivalent immunological solutions to virus neutralization.

Journal Keywords: arenavirus; glycoprotein; structure; antibody response; hemorrhagic fever

Diamond Keywords: Viruses; Argentine Hemorrhagic Fever (AHF)

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I02-Macromolecular Crystallography

Added On: 26/06/2017 10:03

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)