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Science. 2017 Jun 2;356(6341):923-928. doi: 10.1126/science.aam7260.

Structural basis for antibody-mediated neutralization of Lassa virus.

Author information

1
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
3
Zalgen Labs, Germantown, MD, USA.
4
Department of Pediatrics, School of Medicine, Tulane University, New Orleans, LA, USA.
5
Department of Microbiology and Immunology, Tulane University, New Orleans, LA, USA.
6
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. erica@scripps.edu.
7
Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA.

Abstract

The arenavirus Lassa causes severe hemorrhagic fever and a significant disease burden in West Africa every year. The glycoprotein, GPC, is the sole antigen expressed on the viral surface and the critical target for antibody-mediated neutralization. Here we present the crystal structure of the trimeric, prefusion ectodomain of Lassa GP bound to a neutralizing antibody from a human survivor at 3.2-angstrom resolution. The antibody extensively anchors two monomers together at the base of the trimer, and biochemical analysis suggests that it neutralizes by inhibiting conformational changes required for entry. This work illuminates pH-driven conformational changes in both receptor-binding and fusion subunits of Lassa virus, illustrates the unique assembly of the arenavirus glycoprotein spike, and provides a much-needed template for vaccine design against these threats to global health.

PMID:
28572385
PMCID:
PMC6007842
DOI:
10.1126/science.aam7260
[Indexed for MEDLINE]
Free PMC Article

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