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J Virol. Altered receptor specificity and cell tropism of D222G haemagglutinin mutants from fatal cases of pandemic A(H1N1) 2009 influenza
Altered receptor specificity and cell tropism of D222G haemagglutinin mutants from fatal cases of pandemic A(H1N1) 2009 influenza (Abstract, edited)
[Source: Imperial College London, full PDF Document (LINK). Abstract, edited.]
Altered receptor specificity and cell tropism of D222G haemagglutinin mutants from fatal cases of pandemic A(H1N1) 2009 influenza
Yan Liu 1*, Robert A. Childs 1*, Tatyana Matrosovich 2*, Stephen Wharton 3,4 , Angelina S. Palma 4, Wengang Chai 1, Rodney Daniels 3, Victoria Gregory 3, Jennifer Uhlendorff 2,5 , Makoto Kiso 5, Hans-Dieter Klenk 2, Alan Hay 3, Ten Feizi 1** and Mikhail Matrosovich 2** 6
1 The Glycosciences Laboratory, Department of Medicine, Imperial College London, Northwick Park and St. Mark?s Campus, Harrow, Middlesex HA1 3UJ, UK; 2 Institute of Virology, Philipps University, Hans-Meerwein-Str.2, 35043, Marburg, Germany; 3 Division of Virology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK; 4 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; 5 Department of Applied Bioorganic Chemistry, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu, Japan.
* These authors contributed equally to this work.
** Corresponding authors? mailing addresses:
M.M. Institute of Virology, Philipps University, Hans-Meerwein-Str.2, 35043, Marburg, 27 Germany. Phone: 49 6421 286 5166. Fax: 49 6421 286 8962. E-mail: Mikhail.Matrosovich@staff.uni-marburg.de, T.F The Glycosciences Laboratory, Department of Medicine, Imperial College London, Northwick Park and St. Mark?s Campus, Harrow, Middlesex HA1 3UJ, UK. Phone: 44 208 869 3460. Fax: 44 208 8693455. E-mail: t.feizi@imperial.ac.uk.
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.
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[Source: Imperial College London, full PDF Document (LINK). Abstract, edited.]
Altered receptor specificity and cell tropism of D222G haemagglutinin mutants from fatal cases of pandemic A(H1N1) 2009 influenza
Yan Liu 1*, Robert A. Childs 1*, Tatyana Matrosovich 2*, Stephen Wharton 3,4 , Angelina S. Palma 4, Wengang Chai 1, Rodney Daniels 3, Victoria Gregory 3, Jennifer Uhlendorff 2,5 , Makoto Kiso 5, Hans-Dieter Klenk 2, Alan Hay 3, Ten Feizi 1** and Mikhail Matrosovich 2** 6
1 The Glycosciences Laboratory, Department of Medicine, Imperial College London, Northwick Park and St. Mark?s Campus, Harrow, Middlesex HA1 3UJ, UK; 2 Institute of Virology, Philipps University, Hans-Meerwein-Str.2, 35043, Marburg, Germany; 3 Division of Virology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK; 4 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; 5 Department of Applied Bioorganic Chemistry, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu, Japan.
* These authors contributed equally to this work.
** Corresponding authors? mailing addresses:
M.M. Institute of Virology, Philipps University, Hans-Meerwein-Str.2, 35043, Marburg, 27 Germany. Phone: 49 6421 286 5166. Fax: 49 6421 286 8962. E-mail: Mikhail.Matrosovich@staff.uni-marburg.de, T.F The Glycosciences Laboratory, Department of Medicine, Imperial College London, Northwick Park and St. Mark?s Campus, Harrow, Middlesex HA1 3UJ, UK. Phone: 44 208 869 3460. Fax: 44 208 8693455. E-mail: t.feizi@imperial.ac.uk.
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.
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