Changes in the affinity of the hemagglutinin to sialic receptors in the H5 and H9 influenza virus escape mutants

In our earlier studies, mouse-adapted variants of the H5N2 and H9N2 influenza viruses were used to obtain H5 and H9 escape mutants, respectively. All the escape mutants and the wildtype viruses were analyzed to assess the effect of the amino acid changes in the mutants on virulence in mice and affinity toward sialic receptors. Several H9 and H5 escape mutants with a new glycosylation site showed both a decrease in the affinity of the hemagglutinin to the high molecular weight sialic substrates and reduced lethality in mice. The H9 escape mutants with the amino acid L226Q change showed increased affinity for the sialyl substrates with a Sia(2-3)Gal linkage in contrast to the other mutants. The presented data have shown that the decrease in the affinity of the hemagglutinin to the high molecular weight sialic substrates correlates with the decrease in virulence for mice. (C) 2003 Elsevier B.V. All rights reserved.