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Science. Preferential Recognition of Avian-Like Receptors in Human Influenza A H7N9 Viruses
[Source: Science, full page: (LINK). Abstract, edited.]
<CITE><ABBR>Science</ABBR> 6 December 2013: Vol. 342 no. 6163 pp. 1230-1235 / DOI: 10.1126/science.1243761 </CITE>
<CITE></CITE>
<CITE></CITE>Report
Preferential Recognition of Avian-Like Receptors in Human Influenza A H7N9 Viruses
Rui Xu<SUP>1</SUP>, Robert P. de Vries<SUP>2</SUP>, Xueyong Zhu<SUP>1</SUP>, Corwin M. Nycholat<SUP>2</SUP>, Ryan McBride<SUP>2</SUP>, Wenli Yu<SUP>1</SUP>, James C. Paulson<SUP>2</SUP>,*, Ian A. Wilson<SUP>1</SUP>,<SUP>3</SUP>,*
Author Affiliations: <SUP>1</SUP>Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. <SUP>2</SUP>Department of Cell and Molecular Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. <SUP>3</SUP>Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
*Corresponding author. E-mail: wilson@scripps.edu (I.A.W.); jpaulson@scripps.edu (J.C.P.)
Abstract
The 2013 outbreak of avian-origin H7N9 influenza in eastern China has raised concerns about its ability to transmit in the human population. The hemagglutinin glycoprotein of most human H7N9 viruses carries Leu<SUP>226</SUP>, a residue linked to adaptation of H2N2 and H3N2 pandemic viruses to human receptors. However, glycan array analysis of the H7 hemagglutinin reveals negligible binding to humanlike α2-6?linked receptors and strong preference for a subset of avian-like α2-3?linked glycans recognized by all avian H7 viruses. Crystal structures of H7N9 hemagglutinin and six hemagglutinin-glycan complexes have elucidated the structural basis for preferential recognition of avian-like receptors. These findings suggest that the current human H7N9 viruses are poorly adapted for efficient human-to-human transmission.
Avian Affinity for H7N9
Structural analyses of the binding of avian origin H7N9 influenza viruses have revealed how the receptor-binding characteristics differentiate between birds and mammals, and studies involving the use of whole viruses have suggested that the virus is acquiring human-type receptor specificity. In contrast, Xu et al. (p. 1230) show that the H7 hemagglutinin strongly retains its specificity for avian-type receptors by using cocrystal structures with receptor analogs and glycan binding analysis with recombinant hemagglutinin against a library of receptor analogs. Thus, current human H7N9 viruses appear to remain poorly adapted to human receptors, and additional mutations will be required to achieve specificity for human-type receptors equivalent to those of human pandemic viruses.
Received for publication 25 July 2013. Accepted for publication 28 October 2013.
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<CITE><ABBR>Science</ABBR> 6 December 2013: Vol. 342 no. 6163 pp. 1230-1235 / DOI: 10.1126/science.1243761 </CITE>
<CITE></CITE>
<CITE></CITE>Report
Preferential Recognition of Avian-Like Receptors in Human Influenza A H7N9 Viruses
Rui Xu<SUP>1</SUP>, Robert P. de Vries<SUP>2</SUP>, Xueyong Zhu<SUP>1</SUP>, Corwin M. Nycholat<SUP>2</SUP>, Ryan McBride<SUP>2</SUP>, Wenli Yu<SUP>1</SUP>, James C. Paulson<SUP>2</SUP>,*, Ian A. Wilson<SUP>1</SUP>,<SUP>3</SUP>,*
Author Affiliations: <SUP>1</SUP>Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. <SUP>2</SUP>Department of Cell and Molecular Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. <SUP>3</SUP>Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
*Corresponding author. E-mail: wilson@scripps.edu (I.A.W.); jpaulson@scripps.edu (J.C.P.)
Abstract
The 2013 outbreak of avian-origin H7N9 influenza in eastern China has raised concerns about its ability to transmit in the human population. The hemagglutinin glycoprotein of most human H7N9 viruses carries Leu<SUP>226</SUP>, a residue linked to adaptation of H2N2 and H3N2 pandemic viruses to human receptors. However, glycan array analysis of the H7 hemagglutinin reveals negligible binding to humanlike α2-6?linked receptors and strong preference for a subset of avian-like α2-3?linked glycans recognized by all avian H7 viruses. Crystal structures of H7N9 hemagglutinin and six hemagglutinin-glycan complexes have elucidated the structural basis for preferential recognition of avian-like receptors. These findings suggest that the current human H7N9 viruses are poorly adapted for efficient human-to-human transmission.
Avian Affinity for H7N9
Structural analyses of the binding of avian origin H7N9 influenza viruses have revealed how the receptor-binding characteristics differentiate between birds and mammals, and studies involving the use of whole viruses have suggested that the virus is acquiring human-type receptor specificity. In contrast, Xu et al. (p. 1230) show that the H7 hemagglutinin strongly retains its specificity for avian-type receptors by using cocrystal structures with receptor analogs and glycan binding analysis with recombinant hemagglutinin against a library of receptor analogs. Thus, current human H7N9 viruses appear to remain poorly adapted to human receptors, and additional mutations will be required to achieve specificity for human-type receptors equivalent to those of human pandemic viruses.
Received for publication 25 July 2013. Accepted for publication 28 October 2013.
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