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PLoS Pathog . Structural basis for cross-group recognition of an influenza virus hemagglutinin antibody that targets postfusion stabilized epitope

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  • PLoS Pathog . Structural basis for cross-group recognition of an influenza virus hemagglutinin antibody that targets postfusion stabilized epitope


    PLoS Pathog

    . 2023 Aug 9;19(8):e1011554.
    doi: 10.1371/journal.ppat.1011554. eCollection 2023 Aug.
    Structural basis for cross-group recognition of an influenza virus hemagglutinin antibody that targets postfusion stabilized epitope
    Keisuke Tonouchi 1 2 , Yu Adachi 1 , Tateki Suzuki 3 , Daisuke Kuroda 1 , Ayae Nishiyama 1 4 , Kohei Yumoto 1 , Haruko Takeyama 2 5 6 7 , Tadaki Suzuki 8 , Takao Hashiguchi 3 , Yoshimasa Takahashi 1
    Affiliations

    PMID: 37556494 PMCID: PMC10411744 DOI: 10.1371/journal.ppat.1011554

    Free PMC article
    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.

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