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J Virol. 2010 Sep 8. [Epub ahead of print]
Altered receptor specificity and cell tropism of D222G haemagglutinin mutants from fatal cases of pandemic A(H1N1) 2009 influenza.
Liu Y, Childs RA, Matrosovich T, Wharton S, Palma AS, Chai W, Daniels R, Gregory V, Uhlendorff J, Kiso M, Klenk HD, Hay A, Feizi T, Matrosovich M.
The Glycosciences Laboratory, Department of Medicine, Imperial College London, Northwick Park and St. Mark's Campus, Harrow, Middlesex HA1 3UJ, UK; Institute of Virology, Philipps University, Hans-Meerwein-Str.2, 35043, Marburg, Germany; Division of Virology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK; REQUIMTE, Centro de Qu?mica Fina e Biotecnologia, Departamento de Qu?mica, Faculdade de Ci?ncias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal; Department of Applied Bioorganic Chemistry, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu, Japan.
Abstract
Mutations in the receptor-binding site of the haemagglutinin 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 viruses with 222D or 222E which targeted mainly non-ciliated 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.
PMID: 20826688 [PubMed - as supplied by publisher]
Altered receptor specificity and cell tropism of D222G haemagglutinin mutants from fatal cases of pandemic A(H1N1) 2009 influenza.
Liu Y, Childs RA, Matrosovich T, Wharton S, Palma AS, Chai W, Daniels R, Gregory V, Uhlendorff J, Kiso M, Klenk HD, Hay A, Feizi T, Matrosovich M.
The Glycosciences Laboratory, Department of Medicine, Imperial College London, Northwick Park and St. Mark's Campus, Harrow, Middlesex HA1 3UJ, UK; Institute of Virology, Philipps University, Hans-Meerwein-Str.2, 35043, Marburg, Germany; Division of Virology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK; REQUIMTE, Centro de Qu?mica Fina e Biotecnologia, Departamento de Qu?mica, Faculdade de Ci?ncias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal; Department of Applied Bioorganic Chemistry, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu, Japan.
Abstract
Mutations in the receptor-binding site of the haemagglutinin 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 viruses with 222D or 222E which targeted mainly non-ciliated 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.
PMID: 20826688 [PubMed - as supplied by publisher]
