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    N-linked glycans on influenza A H3N2 hemagglutinin constrain binding of host antibodies, but shielding is limited

    Pentiah, Kevin and Lees, William D. and Moss, David S. and Shepherd, Adrian J. (2015) N-linked glycans on influenza A H3N2 hemagglutinin constrain binding of host antibodies, but shielding is limited. Glycobiology 25 (1), pp. 124-132. ISSN 0959-6658.

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    Abstract

    The extent of the role of N-linked glycans (N-glycans) in shielding influenza A hemagglutinin against host antibodies has proved controversial, with different authors making widely different assumptions. One common assumption is that N-glycans physically shield surface residues that are near to glycosylation sites, thereby preventing antibodies from binding to them. However, it is unclear, from existing experimental evidence, whether antibodies that bind close to N-glycans are a rare or commonplace feature of human herd immune responses to influenza A hemagglutinin. The aim of this paper is to present a computational analysis of mutations in the vicinity of N-glycans that will facilitate a better understanding of their protective role. We identify, from an analysis of over 6,000 influenza A H3N2 sequences, a set of residues adjacent to N-glycosylation sites that are highly likely to be involved in antigenic escape from host antibodies. Fifteen of these residues occur within 10Å of an N-glycosylation site. Hence we conclude that it is relatively common for antibodies to bind in close proximity to N-glycans on the surface of hemagglutinin, with any shielding effect largely attributable to the inability of host antibodies to bind across an N-glycan attachment site, rather than to the physical masking of neighbouring residues.

    Metadata

    Item Type: Article
    Keyword(s) / Subject(s): bioinformatics, hemagglutinin, influenza A, N-glycans
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Research Centre: Bioinformatics, Bloomsbury Centre for, Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Administrator
    Date Deposited: 18 Sep 2014 10:11
    Last Modified: 07 Dec 2016 15:02
    URI: http://eprints.bbk.ac.uk/id/eprint/10541

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