Glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities

James Stevens, Ola Blixt, Laurel Glaser, Jeffery K. Taubenberger, Peter Palese, James C. Paulson, Ian A. Wilson

Research output: Contribution to journalArticlepeer-review

547 Scopus citations


Influenza A virus specificity for the host is mediated by the viral surface glycoprotein hemagglutinin (HA), which binds to receptors containing glycans with terminal sialic acids. Avian viruses preferentially bind to α2-3-linked sialic acids on receptors of intestinal epithelial cells, whereas human viruses are specific for the α2-6 linkage on epithelial cells of the lungs and upper respiratory tract. To define the receptor preferences of a number of human and avian H1 and H3 viruses, including the 1918 H1N1 pandemic strains, their hemagglutinins were analyzed using a recently described glycan array. The array, which contains 200 carbohydrates and glycoproteins, not only revealed clear differentiation of receptor preferences for α2-3 and/or α2-6 sialic acid linkage, but could also detect fine differences in HA specificity, such as preferences for fucosylation, sulfation and sialylation at positions 2 (Gal) and 3 (GlcNAc, GalNAc) of the terminal trisaccharide. For the two 1918 HA variants, the South Carolina (SC) HA (with Asp190, Asp225) bound exclusively α2-6 receptors, while the New York (NY) variant, which differed only by one residue (Gly225), had mixed α2-6/α2-3 specificity, especially for sulfated oligosaccharides. Only one mutation of the NY variant (Asp190Glu) was sufficient to revert the HA receptor preference to that of classical avian strains. Thus, the species barrier, as defined by the receptor specificity preferences of 1918 human viruses compared to likely avian virus progenitors, can be circumvented by changes at only two positions in the HA receptor binding site. The glycan array thus provides highly detailed profiles of influenza receptor specificity that can be used to map the evolution of new human pathogenic strains, such as the H5N1 avian influenza.

Original languageEnglish
Pages (from-to)1143-1155
Number of pages13
JournalJournal of Molecular Biology
Issue number5
StatePublished - 3 Feb 2006


  • 1918 pandemic
  • Glycoarray
  • Hemagglutinin
  • Influenza
  • Receptor specificity


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