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Recent Avian H5N1 Viruses Exhibit Increased Propensity for Acquiring Human Receptor Specificity [ScienceDirect]
doi:10.1016/j.jmb.2008.04.016
Copyright ? 2008 Elsevier Ltd All rights reserved.
Recent Avian H5N1 Viruses Exhibit Increased Propensity for Acquiring Human Receptor Specificity
James Stevens1, Ola Blixt1, 2, 1, Li-Mei Chen3, Ruben O. Donis3, James C. Paulson1, 2 and Ian A. Wilson1, 4
1Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
2Department of Chemical Physiology and Glycan Array Synthesis Core of the Consortium for Functional Glycomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
3Influenza Division, Molecular Virology Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA
4Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Received 24 February 2008; revised 4 April 2008; accepted 7 April 2008.
Edited by J. Karn.
Available online 11 April 2008.
Abstract
Adaptation of avian influenza viruses for replication and transmission in the human host is believed to require mutations in the hemagglutinin glycoprotein (HA) which enable binding to human α2-6 sialosides and concomitant reduction in affinity for avian α2-3 linked sialosides.
Here, we show by glycan microarray analyses that the two mutations responsible for such specificity changes in 1957 H2N2 and 1968 H3N2 pandemic viruses, when inserted into recombinant HAs or intact viruses of some recent avian H5N1 isolates (clade 2.2), impart such attributes.
This propensity to adapt to human receptors is primarily dependent on arginine at position 193 within the receptor-binding site, as well as loss of a vicinal glycosylation site.
Widespread occurrence of these susceptible H5N1 clade 2.2 influenza strains has already occurred in Europe, the Middle East, and Africa.
Thus, these avian strains should be considered high-risk, because of their significantly lower threshold for acquiring human receptor specificity and, therefore, warrant increased surveillance and further study.
Keywords: influenza; glycan array; hemagglutinin; receptor specificity; H5N1Abbreviations: HA, hemagglutinin; rHA, recombinant HA
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<cite cite="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WK7-4S85DTV-3&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view =c&_version=1&_urlVersion=0&_userid=10&md5=7b4dea0 57afc07d0f2103783e9e35c82">ScienceDirect - Journal of Molecular Biology : Recent Avian H5N1 Viruses Exhibit Increased Propensity for Acquiring Human Receptor Specificity</cite>
Copyright ? 2008 Elsevier Ltd All rights reserved.
Recent Avian H5N1 Viruses Exhibit Increased Propensity for Acquiring Human Receptor Specificity
James Stevens1, Ola Blixt1, 2, 1, Li-Mei Chen3, Ruben O. Donis3, James C. Paulson1, 2 and Ian A. Wilson1, 4
1Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
2Department of Chemical Physiology and Glycan Array Synthesis Core of the Consortium for Functional Glycomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
3Influenza Division, Molecular Virology Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA
4Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Received 24 February 2008; revised 4 April 2008; accepted 7 April 2008.
Edited by J. Karn.
Available online 11 April 2008.
Abstract
Adaptation of avian influenza viruses for replication and transmission in the human host is believed to require mutations in the hemagglutinin glycoprotein (HA) which enable binding to human α2-6 sialosides and concomitant reduction in affinity for avian α2-3 linked sialosides.
Here, we show by glycan microarray analyses that the two mutations responsible for such specificity changes in 1957 H2N2 and 1968 H3N2 pandemic viruses, when inserted into recombinant HAs or intact viruses of some recent avian H5N1 isolates (clade 2.2), impart such attributes.
This propensity to adapt to human receptors is primarily dependent on arginine at position 193 within the receptor-binding site, as well as loss of a vicinal glycosylation site.
Widespread occurrence of these susceptible H5N1 clade 2.2 influenza strains has already occurred in Europe, the Middle East, and Africa.
Thus, these avian strains should be considered high-risk, because of their significantly lower threshold for acquiring human receptor specificity and, therefore, warrant increased surveillance and further study.
Keywords: influenza; glycan array; hemagglutinin; receptor specificity; H5N1Abbreviations: HA, hemagglutinin; rHA, recombinant HA
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