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Insight into highly conserved h1 subtype-specific epitopes in influenza virus hemagglutinin

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  • Insight into highly conserved h1 subtype-specific epitopes in influenza virus hemagglutinin

    PLoS One. 2014 Feb 26;9(2):e89803. doi: 10.1371/journal.pone.0089803. eCollection 2014.
    Insight into highly conserved h1 subtype-specific epitopes in influenza virus hemagglutinin.
    Cho KJ1, Hong KW2, Kim SH2, Seok JH1, Kim S1, Lee JH1, Saelens X3, Kim KH1.
    Author information
    Abstract

    Influenza viruses continuously undergo antigenic changes with gradual accumulation of mutations in hemagglutinin (HA) that is a major determinant in subtype specificity. The identification of conserved epitopes within specific HA subtypes gives an important clue for developing new vaccines and diagnostics. We produced and characterized nine monoclonal antibodies that showed significant neutralizing activities against H1 subtype influenza viruses, and determined the complex structure of HA derived from a 2009 pandemic virus A/Korea/01/2009 (KR01) and the Fab fragment from H1-specific monoclonal antibody GC0587. The overall structure of the complex was essentially identical to the previously determined KR01 HA-Fab0757 complex structure. Both Fab0587 and Fab0757 recognize readily accessible head regions of HA, revealing broadly shared and conserved antigenic determinants among H1 subtypes. The β-strands constituted by Ser110-Glu115 and Lys169-Lys170 form H1 epitopes with distinct conformations from those of H1 and H3 HA sites. In particular, Glu112, Glu115, Lys169, and Lys171 that are highly conserved among H1 subtype HAs have close contacts with HCDR3 and LCDR3. The differences between Fab0587 and Fab0757 complexes reside mainly in HCDR3 and LCDR3, providing distinct antigenic determinants specific for 1918 pdm influenza strain. Our results demonstrate a potential key neutralizing epitope important for H1 subtype specificity in influenza virus.

    PMID:
    24587046
    [PubMed - in process]

    Free full text

    Influenza viruses continuously undergo antigenic changes with gradual accumulation of mutations in hemagglutinin (HA) that is a major determinant in subtype specificity. The identification of conserved epitopes within specific HA subtypes gives an important clue for developing new vaccines and diagn …
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