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N ‐linked glycosylation of Hemagglutinin Globular Head Modulates the Antibody Response to H3N2 Influenza A Virus
Author(s) -
Alymova Irina
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.618.1
Subject(s) - hemagglutinin (influenza) , avidity , virology , virus , biology , antibody , titer , influenza a virus , glycosylation , hemagglutination assay , microbiology and biotechnology , immunology , biochemistry
Molecular evolution of humanH3N2 influenza A viruses (IAV) has included the progressive addition of N ‐linked glycans onto the hemagglutinin(HA) globular head. The pandemic H3N2 virus A/Hong Kong/1/1968 (HK68) possessed only two glycosylation sites on the HA globular head at residues 81 and 165. In 1975 and 1999, periods of significant antigenic change, H3N2 IAV acquiredglycans at residues 63 and 126 (HK68+2) and residues 63, 126, 133, and 246(HK68+4), respectively. Differences in receptor binding, pathogenicity, and induction of T‐cell‐mediated immunopathology in mice between the HK68 and its glycosylation variants have previously been demonstrated. Here, we evaluated the consequences of this incremental glycosylation on antibody responses directed to HA. Total serum antibody titers against HA were measured 15 days after infection of mice with 10 5 TCID 50 of each virus by hemagglutination inhibition assay (HI) with various red blood cells (RBC) at room temperature (RT). The avidity was measured at 37°C. Sera from mice infected with any virus showed reactivity against all tested HAs. However, sera from mice infected with HK68 and HK68+2 (lower glycosylation) demonstrated relatively low reactivity against higher glycosylated HK68+4. Sera from HK68+4‐infected mice recognized all tested HAs at similar levels. Viral pathogenicity did not correlate with antibody titers or avidity, since moderate titers and avidity were observed with viruses of highest and lowest pathogenicity (HK68 and HK69+4 respectively), while higher titers and avidity were seen in sera of mice infected with HK68+2, whose pathogenicity is intermediate between HK69 and HK68+4. The data suggest that HA antibody responses may be influenced by HA glycan composition in ways that are unconnected to pathogenicity. Modification of N ‐linked glycosylation of the HA globular head may present a new approach for improvement of IAV vaccine efficacy.