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Glycobiology. 2015 Jan;25(1):124-32. doi: 10.1093/glycob/cwu097. Epub 2014 Sep 16.

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

Author information

1
Department of Biological Sciences and Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
2
Department of Biological Sciences and Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK a.shepherd@mail.cryst.bbk.ac.uk.

Abstract

The extent of the role of N-linked glycans (N-glycans) in shielding influenza A hemagglutinin (HA) 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 AHA. 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 6000 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 10 Å 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 ofHA, 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 neighboring residues.

KEYWORDS:

N-glycans; bioinformatics; hemagglutinin; influenza A

PMID:
25227423
DOI:
10.1093/glycob/cwu097
[Indexed for MEDLINE]

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