Convergent immunological solutions to Argentine hemorrhagic fever virus neutralization

Zeltina, Antra and Krumm, Stefanie A. and Sahin, Mehmet and Struwe, Weston B. and Harlos, Karl and Nunberg, Jack H. and Crispin, Max and Pinschewer, Daniel D. and Doores, Katie J. and Bowden, Thomas A.. (2017) Convergent immunological solutions to Argentine hemorrhagic fever virus neutralization. Proceedings of the National Academy of Sciences of the United States of America, 114 (27). pp. 7031-7036.

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Official URL: https://edoc.unibas.ch/76563/

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Experimental Virology (Pinschewer)
UniBasel Contributors:Pinschewer, Daniel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Aug 2020 15:01
Deposited On:20 Aug 2020 15:01

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