In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 8 ( 2023-8-9), p. e1011554-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011554
DOI:
10.1371/journal.ppat.1011554.g001
DOI:
10.1371/journal.ppat.1011554.g002
DOI:
10.1371/journal.ppat.1011554.g003
DOI:
10.1371/journal.ppat.1011554.g004
DOI:
10.1371/journal.ppat.1011554.g005
DOI:
10.1371/journal.ppat.1011554.s001
DOI:
10.1371/journal.ppat.1011554.s002
DOI:
10.1371/journal.ppat.1011554.s003
DOI:
10.1371/journal.ppat.1011554.s004
DOI:
10.1371/journal.ppat.1011554.s005
DOI:
10.1371/journal.ppat.1011554.s006
DOI:
10.1371/journal.ppat.1011554.s007
DOI:
10.1371/journal.ppat.1011554.s008
DOI:
10.1371/journal.ppat.1011554.s009
DOI:
10.1371/journal.ppat.1011554.s010
DOI:
10.1371/journal.ppat.1011554.s011
DOI:
10.1371/journal.ppat.1011554.s012
DOI:
10.1371/journal.ppat.1011554.s013
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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