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J Virol. 2009 Feb 11. [Epub ahead of print]
Role of sialic acid binding specificity of the 1918 influenza virus hemagglutinin protein in virulence and pathogenesis in mice.
Qi L, Kash JC, Dugan VG, Wang R, Jin G, Cunningham RE, Taubenberger JK. - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA; Department of Biophysics, Armed Forces Institute of Pathology, Rockville, MD 20850, USA.
The 1918 influenza pandemic caused over 40 million deaths and likely resulted from 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 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 in mice with similar pathology and cellular tropism.
Changing alpha2-3 to alpha2-6 binding specificity did not increase lethality of an avian adapted hemagglutinin.
Thus, the 1918 hemagglutinin contains murine virulence determinants independent of receptor binding specificity.
PMID: 19211766 [PubMed - as supplied by publisher]
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Role of sialic acid binding specificity of the 1918 influenza virus hemagglutinin protein in virulence and pathogenesis in mice.
Qi L, Kash JC, Dugan VG, Wang R, Jin G, Cunningham RE, Taubenberger JK. - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA; Department of Biophysics, Armed Forces Institute of Pathology, Rockville, MD 20850, USA.
The 1918 influenza pandemic caused over 40 million deaths and likely resulted from 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 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 in mice with similar pathology and cellular tropism.
Changing alpha2-3 to alpha2-6 binding specificity did not increase lethality of an avian adapted hemagglutinin.
Thus, the 1918 hemagglutinin contains murine virulence determinants independent of receptor binding specificity.
PMID: 19211766 [PubMed - as supplied by publisher]
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