Structural basis of synergistic neutralization of Crimean-Congo hemorrhagic fever virus by human antibodies - Archive ouverte HAL Access content directly
Journal Articles iScience Year : 2022

Structural basis of synergistic neutralization of Crimean-Congo hemorrhagic fever virus by human antibodies

(1) , (2, 3) , (4) , (2, 3) , (5, 3) , (6) , (7) , (8) , (8) , (7) , (6) , (4) , (1) , (2)
1
2
3
4
5
6
7
8
Akaash K Mishra
Daniel P Maurer
  • Function : Author
Laura M Walker

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is the most widespread tick-borne zoonotic virus, with a 30% case fatality rate in humans. Structural information is lacking in regard to the CCHFV membrane fusion glycoprotein Gc-the main target of the host neutralizing antibody response-as well as antibody-mediated neutralization mechanisms. We describe the structure of prefusion Gc bound to the antigen-binding fragments (Fabs) of two neutralizing antibodies that display synergy when combined, as well as the structure of trimeric, postfusion Gc. The structures show the two Fabs acting in concert to block membrane fusion, with one targeting the fusion loops and the other blocking Gc trimer formation. The structures also revealed the neutralization mechanism of previously reported antibodies against CCHFV, providing the molecular underpinnings essential for developing CCHFVspecific medical countermeasures for epidemic preparedness.
Fichier principal
Vignette du fichier
science.abl6502.pdf (2.8 Mo) Télécharger le fichier
Origin : Publication funded by an institution

Dates and versions

pasteur-03525373 , version 1 (13-01-2022)

Licence

Attribution - CC BY 4.0

Identifiers

Cite

Akaash K Mishra, Jan Hellert, Natalia Freitas, Pablo Guardado-Calvo, Ahmed Haouz, et al.. Structural basis of synergistic neutralization of Crimean-Congo hemorrhagic fever virus by human antibodies. iScience, 2022, 375 (6576), pp.104-109. ⟨10.1126/science.abl6502⟩. ⟨pasteur-03525373⟩
74 View
129 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More