title: Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus.
abstract: Mutations in the receptor-binding site of the hemagglutinin of pandemic influenza A(H1N1) 2009 viruses have been detected sporadically. An Asp222Gly (D222G) substitution has been associated with severe or fatal disease. Here we show that 222G variants infected a higher proportion of ciliated cells in cultures of human airway epithelium than did viruses with 222D or 222E, which targeted mainly nonciliated cells. Carbohydrate microarray analyses showed that 222G variants bind a broader range of α2-3-linked sialyl receptor sequences of a type expressed on ciliated bronchial epithelial cells and on epithelia within the lung. These features of 222G mutants may contribute to exacerbation of disease.
authors.affiliation: The Glycosciences Laboratory, Department of Medicine, Imperial College London, UK.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Childs
authors.forename: Tatyana
authors.initials: T
authors.lastname: Matrosovich
authors.forename: Stephen
authors.initials: S
authors.lastname: Wharton
authors.forename: Angelina S
authors.initials: AS
authors.lastname: Palma
authors.forename: Wengang
authors.initials: W
authors.lastname: Chai
authors.forename: Rodney
authors.initials: R
authors.lastname: Daniels
authors.forename: Victoria
authors.initials: V
authors.lastname: Gregory
authors.forename: Jennifer
authors.initials: J
authors.lastname: Uhlendorff
authors.forename: Makoto
authors.initials: M
authors.lastname: Kiso
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Klenk
authors.forename: Alan
authors.initials: A
authors.lastname: Hay
authors.forename: Ten
authors.initials: T
authors.lastname: Feizi
authors.forename: Mikhail
authors.initials: M
authors.lastname: Matrosovich
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D004285:Dogs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D007251:Influenza, Human / Q000453:epidemiology / Q000378:metabolism / Q000821:virology*; D020125:Mutation, Missense; D058873:Pandemics; D011485:Protein Binding; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D056189:Viral Tropism
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus
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