Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus

Yan Liu, Robert A. Childs, Tatyana Matrosovich, Stephen Wharton, Angelina S. Palma, Wengang Chai, Rodney Daniels, Victoria Gregory, Jennifer Uhlendorff, Makoto Kiso, Hans Dieter Klenk, Alan Hay, Ten Feizi, Mikhail Matrosovich

Research output: Contribution to journalArticle

157 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)12069-12074
Number of pages6
JournalJournal of Virology
Volume84
Issue number22
DOIs
Publication statusPublished - 1 Nov 2010

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