[SIZE=-1]http://jvi.asm.org/cgi/content/abstract/81/20/11170
Journal of Virology, October 2007, p. 11170-11178, Vol. 81, No. 20
0022-538X/07/$08.00+0 doi:10.1128/JVI.01217-07
Copyright ? 2007, American Society for Microbiology. All Rights Reserved.[/SIZE]
Alterations in Receptor Binding Properties of Recent Human Influenza H3N2 Viruses Are Associated with Reduced Natural Killer Cell Lysis of Infected Cells<sup>
</sup>
Rachel E. Owen,<sup>1</sup><sup>,
</sup><sup>,
</sup> Eriko Yamada,<sup>1</sup><sup>,
</sup><sup>,
</sup> Catherine I. Thompson,<sup>2</sup><sup>,
</sup> Louisa J. Phillipson,<sup>2</sup><sup>,3</sup> Clare Thompson,<sup>1</sup> Elizabeth Taylor,<sup>1</sup> Maria Zambon,<sup>5</sup> Helen M. I. Osborn,<sup>3</sup><sup>,4</sup> Wendy S. Barclay,<sup>2</sup><sup>*</sup> and Persephone Borrow<sup>1</sup> The Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom,<sup>1</sup> School of Biological Sciences, The University of Reading, Whiteknights, Reading RG6 6AJ, United Kingdom,<sup>2</sup> School of Chemistry,<sup>3</sup> School of Pharmacy, The University of Reading, Whiteknights, Reading RG6 6AD, United Kingdom,<sup>4</sup> Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5HT, United Kingdom<sup>5</sup>
Received 4 June 2007/ Accepted 20 July 2007
<!-- ABS --> Natural killer (NK) cell recognition of influenza virus-infected<sup> </sup>cells involves hemagglutinin (HA) binding to sialic acid (SA)<sup> </sup>on activating NK receptors. SA also acts as a receptor for the<sup> </sup>binding of influenza virus to its target host cells. The SA<sup> </sup>binding properties of H3N2 influenza viruses have been observed<sup> </sup>to change during circulation in humans: recent isolates are<sup> </sup>unable to agglutinate chicken red blood cells and show reduced<sup> </sup>affinity for synthetic glycopolymers representing SA-
-2,3-lactose<sup> </sup>(3'SL-PAA) and SA-
-2,6-N-acetyl lactosamine (6'SLN-PAA) carbohydrates.<sup> </sup>Here, NK lysis of cells infected with human H3N2 influenza viruses<sup> </sup>isolated between 1969 and 2003 was analyzed. Cells infected<sup> </sup>with recent isolates (1999 to 2003) were found to be lysed less<sup> </sup>effectively than cells infected with older isolates (1969 to<sup> </sup>1996). This change occurred concurrently with the acquisition<sup> </sup>of two new potential glycosylation site motifs in HA. Deletion<sup> </sup>of the potential glycosylation site motif at 133 to 135 in HA1<sup> </sup>from a recent isolate partially restored the agglutination phenotype<sup> </sup>to a recombinant virus, indicating that the HA-SA interaction<sup> </sup>is inhibited by the glycosylation modification. Deletion of<sup> </sup>either of the recently acquired potential glycosylation sites<sup> </sup>from HA led to increased NK lysis of cells infected with recombinant<sup> </sup>viruses carrying modified HA. These results indicate that alterations<sup> </sup>in HA glycosylation may affect NK cell recognition of influenza<sup> </sup>virus-infected cells in addition to virus binding to host cells.
Journal of Virology, October 2007, p. 11170-11178, Vol. 81, No. 20
0022-538X/07/$08.00+0 doi:10.1128/JVI.01217-07
Copyright ? 2007, American Society for Microbiology. All Rights Reserved.[/SIZE]
Alterations in Receptor Binding Properties of Recent Human Influenza H3N2 Viruses Are Associated with Reduced Natural Killer Cell Lysis of Infected Cells<sup>
Rachel E. Owen,<sup>1</sup><sup>,
Received 4 June 2007/ Accepted 20 July 2007
<!-- ABS --> Natural killer (NK) cell recognition of influenza virus-infected<sup> </sup>cells involves hemagglutinin (HA) binding to sialic acid (SA)<sup> </sup>on activating NK receptors. SA also acts as a receptor for the<sup> </sup>binding of influenza virus to its target host cells. The SA<sup> </sup>binding properties of H3N2 influenza viruses have been observed<sup> </sup>to change during circulation in humans: recent isolates are<sup> </sup>unable to agglutinate chicken red blood cells and show reduced<sup> </sup>affinity for synthetic glycopolymers representing SA-