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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 ?2-3-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.

SUBMITTER: Liu Y 

PROVIDER: S-EPMC2977873 | biostudies-other | 2010 Nov

REPOSITORIES: biostudies-other

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

Liu Yan Y   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  

Journal of virology 20100908 22


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  ...[more]

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