Qi, L., Kash, J. C., Dugan, V. G., Wang, R., Jin, G., Cunningham, R. E., Taubenberger, J. K.
Role of Sialic Acid Binding Specificity of the 1918 Influenza Virus Hemagglutinin Protein In Virulence and Pathogenesis for Mice
J Virol. 2009 Apr 01; 83(8): 3754-61.
The 1918 influenza pandemic caused more than 40 million deaths and likely resulted from the introduction and adaptation of a novel avian-like virus. Influenza A virus hemagglutinins are important in host switching and virulence. Avian-adapted influenza virus hemagglutinins bind sialic acid receptors linked via alpha2-3 glycosidic bonds, while human-adapted hemagglutinins bind alpha2-6 receptors. Sequence analysis of 1918 isolates showed hemagglutinin genes with alpha2-6 or mixed alpha2-6/alpha2-3 binding. To characterize the role of the sialic acid binding specificity of the 1918 hemagglutinin, we evaluated in mice chimeric influenza viruses expressing wild-type and mutant hemagglutinin genes from avian and 1918 strains with differing receptor specificities. Viruses expressing 1918 hemagglutinin possessing either alpha2-6, alpha2-3, or alpha2-3/alpha2-6 sialic acid specificity were fatal to mice, with similar pathology and cellular tropism. Changing alpha2-3 to alpha2-6 binding specificity did not increase the lethality of an avian-adapted hemagglutinin. Thus, the 1918 hemagglutinin contains murine virulence determinants independent of receptor binding specificity.
This publication is listed for reference purposes only. It may be included to present a more complete view of a JCVI employee's body of work, or as a reference to a JCVI sponsored project.