Structural basis of synergistic neutralization of Crimean-Congo hemorrhagic fever virus by human antibodies.
Antibodies, Neutralizing
/ chemistry
Antibodies, Viral
/ chemistry
Crystallography, X-Ray
Epitopes
/ chemistry
Hemorrhagic Fever Virus, Crimean-Congo
/ immunology
Humans
Immunoglobulin Fab Fragments
/ chemistry
Models, Molecular
Neutralization Tests
Protein Binding
Protein Conformation
Protein Domains
Protein Folding
Protein Multimerization
Viral Fusion Proteins
/ chemistry
Virus Internalization
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
07 Jan 2022
07 Jan 2022
Historique:
pubmed:
19
11
2021
medline:
15
1
2022
entrez:
18
11
2021
Statut:
ppublish
Résumé
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 CCHFV–specific medical countermeasures for epidemic preparedness.
Identifiants
pubmed: 34793197
doi: 10.1126/science.abl6502
pii: 10.1126/science.abl6502
pmc: PMC9771711
mid: NIHMS1858267
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Epitopes
0
Immunoglobulin Fab Fragments
0
Viral Fusion Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104-109Subventions
Organisme : NIAID NIH HHS
ID : U19 AI142777
Pays : United States
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