Role of sialic acid binding specificity of the 1918 influenza virus hemagglutinin protein in virulence and pathogenesis for mice.

ABSTRACT: 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.

SUBMITTER: Qi L 

PROVIDER: S-EPMC2663248 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature