Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus.
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.
Liu
Yan
Y
The Glycosciences Laboratory, Department of Medicine, Imperial College London, UK.
Childs
Robert A
RA
Matrosovich
Tatyana
T
Wharton
Stephen
S
Palma
Angelina S
AS
Chai
Wengang
W
Daniels
Rodney
R
Gregory
Victoria
V
Uhlendorff
Jennifer
J
Kiso
Makoto
M
Klenk
Hans-Dieter
HD
Hay
Alan
A
Feizi
Ten
T
Matrosovich
Mikhail
M
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
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus
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