Orthobunyavirus spike architecture and recognition by neutralizing antibodies

Nature Communications
Jan HellertFélix A Rey

Abstract

Orthobunyaviruses (OBVs) form a distinct genus of arthropod-borne bunyaviruses that can cause severe disease upon zoonotic transmission to humans. Antigenic drift or genome segment re-assortment have in the past resulted in new pathogenic OBVs, making them potential candidates for causing emerging zoonoses in the future. Low-resolution electron cryo-tomography studies have shown that OBV particles feature prominent trimeric spikes, but their molecular organization remained unknown. Here we report X-ray crystallography studies of four different OBVs showing that the spikes are formed by an N-terminal extension of the fusion glycoprotein Gc. Using Schmallenberg virus, a recently emerged OBV, we also show that the projecting spike is the major target of the neutralizing antibody response, and provide X-ray structures in complex with two protecting antibodies. We further show that immunization of mice with the spike domains elicits virtually sterilizing immunity, providing fundamental knowledge essential in the preparation for potential newly emerging OBV zoonoses.

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Citations

Dec 6, 2019·Journal of Virology·Bernardo GutierrezOliver G Pybus
Jan 31, 2020·Journal of Virology·Akaash K MishraJason S McLellan
Jun 10, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Philippe PérotMarc Eloit
Jun 12, 2020·Vaccines·Kerstin Wernike, Martin Beer
Apr 22, 2020·ELife·Paul J Wichgers SchreurJeroen Kortekaas
Apr 23, 2020·Transboundary and Emerging Diseases·Kerstin Wernike, Martin Beer
Oct 7, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yoav BahatMoshe Dessau
Jun 3, 2021·Viruses·Stefan WindhaberPierre-Yves Lozach

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Methods Mentioned

BETA
X-ray
protein folding
glycosylation
electron cryo-tomography
ELISA
biolayer interferometry
size exclusion chromatography
FCS
transfection
affinity purification

Software Mentioned

SHELXE
Elements Imaging Basic Research
Octet Data Analysis HT
Phenix
Clustal Omega
Coot
UCSF Chimera
NIS
Phyre
SigmaPlot

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