Structural basis for cross-group recognition of an influenza virus hemagglutinin antibody that targets postfusion stabilized epitope.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
10
03
2023
accepted:
11
07
2023
medline:
11
8
2023
pubmed:
9
8
2023
entrez:
9
8
2023
Statut:
epublish
Résumé
Plasticity of influenza virus hemagglutinin (HA) conformation increases an opportunity to generate conserved non-native epitopes with unknown functionality. Here, we have performed an in-depth analysis of human monoclonal antibodies against a stem-helix region that is occluded in native prefusion yet exposed in postfusion HA. A stem-helix antibody, LAH31, provided IgG Fc-dependent cross-group protection by targeting a stem-helix kinked loop epitope, with a unique structure emerging in the postfusion state. The structural analysis and molecular modeling revealed key contact sites responsible for the epitope specificity and cross-group breadth that relies on somatically mutated light chain. LAH31 was inaccessible to the native prefusion HA expressed on cell surface; however, it bound to the HA structure present on infected cells with functional linkage to the Fc-mediated clearance. Our study uncovers a novel non-native epitope that emerges in the postfusion HA state, highlighting the utility of this epitope for a broadly protective antigen design.
Identifiants
pubmed: 37556494
doi: 10.1371/journal.ppat.1011554
pii: PPATHOGENS-D-23-00448
pmc: PMC10411744
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Epitopes
0
Hemagglutinin Glycoproteins, Influenza Virus
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1011554Informations de copyright
Copyright: © 2023 Tonouchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
KT, YA, and YT declare that an intellectual property application has been filed for the LAH31 antibody.
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