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PMID: 19211766 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

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

Journal of virology ·Vol. 83 ·No. 8 ·2009-04-00 ·Pages 3754-61

Qi L, Kash JC, Dugan VG, Wang R, Jin G, Cunningham RE, Taubenberger JK

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.

MeSH Terms
Animals Female Hemagglutinin Glycoproteins, Influenza Virus/genetics,metabolism Influenza A Virus, H1N1 Subtype/growth & development,pathogenicity,physiology Mice Mice, Inbred BALB C Molecular Sequence Data N-Acetylneuraminic Acid/metabolism Orthomyxoviridae Infections/virology Protein Binding Sequence Analysis, DNA Survival Analysis Virulence Virus Attachment
Chemicals
Hemagglutinin Glycoproteins, Influenza Virus hemagglutinin, human influenza A virus N-Acetylneuraminic Acid
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Qi Li
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 208921, USA.
Kash John C
Dugan Vivien G
Wang Ruixue
Jin Guozhong
Cunningham Robert E
Taubenberger Jeffery K
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
1098-5514
DOI
10.1128/JVI.02596-08
Published
2009-04-00
Epub
2009-00-11
Pages
3754-61
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC2663248
Subset
IM
Grants
Intramural NIH HHS · United States
Databases
GENBANK
FJ770051, FJ770052, FJ770053, FJ770054, FJ770055, FJ770056, FJ770057, FJ770058
External Links
PubMed source DOI: 10.1128/JVI.02596-08 PMC Full Text View journal details
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