Emily
Editor, Senior Moderator
I wasn't sure where to put this. There is a 'Significance for virulence' section in this paper, too, and it has some interesting findings and theories about the 1918 presentations. I see this paper was cited here on the forum previously, but at the time the full text was not available for everyone.
Full text pdf available here.
(Received 31 October 2005; accepted 4 November 2005)
Available online 18 November 2005
Glycan Microarray Analysis of the Hemagglutinins from
Modern and Pandemic Influenza Viruses Reveals
Different Receptor Specificities
James Stevens1?, Ola Blixt1,2?, Laurel Glaser3, Jeffery K. Taubenberger4
Peter Palese3, James C. Paulson1,2* and Ian A. Wilson1,5*
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 a2-3-
linked sialic acids on receptors of intestinal epithelial cells, whereas human
viruses are specific for the a2-6 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
a2-3 and/or a2-6 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 a2-6 receptors, while the New
York (NY) variant, which differed only by one residue (Gly225), had mixed
a2-6/a2-3 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.
Full text pdf available here.
(Received 31 October 2005; accepted 4 November 2005)
Available online 18 November 2005
Glycan Microarray Analysis of the Hemagglutinins from
Modern and Pandemic Influenza Viruses Reveals
Different Receptor Specificities
James Stevens1?, Ola Blixt1,2?, Laurel Glaser3, Jeffery K. Taubenberger4
Peter Palese3, James C. Paulson1,2* and Ian A. Wilson1,5*
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 a2-3-
linked sialic acids on receptors of intestinal epithelial cells, whereas human
viruses are specific for the a2-6 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
a2-3 and/or a2-6 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 a2-6 receptors, while the New
York (NY) variant, which differed only by one residue (Gly225), had mixed
a2-6/a2-3 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.