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Virology. Enhanced human receptor binding by H5 haemagglutinins

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  • Virology. Enhanced human receptor binding by H5 haemagglutinins

    [Source: Science Direct, full page: (LINK). Abstract, edited.]


    Virology, Volumes 456?457, May 2014, Pages 179?187

    Enhanced human receptor binding by H5 haemagglutinins

    Xiaoli Xiong, Haixia Xiao<SUP>1</SUP>, Stephen R. Martin, Peter J. Coombs, Junfeng Liu, Patrick J. Collins, Sebastien G. Vachieri, Philip A. Walker, Yi Pu Lin, John W. McCauley, Steven J. Gamblin, John J. Skehel

    1)MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK

    Received 13 January 2014, Revised 10 February 2014, Accepted 7 March 2014, Available online 12 April 2014 / Open Access funded by Medical Research Council - License: http://creativecommons.org/licenses/by/3.0/ / http://dx.doi.org/10.1016/j.virol.2014.03.008


    Highlights
    • H5N1 influenza virus binding.
    • Haemagglutinin receptor specificity using biolayer interferometry.
    • Haemagglutinin receptor complex crystal structure determination.


    Abstract

    Mutant H5N1 influenza viruses have been isolated from humans that have increased human receptor avidity. We have compared the receptor binding properties of these mutants with those of wild-type viruses, and determined the structures of their haemagglutinins in complex with receptor analogues. Mutants from Vietnam bind tighter to human receptor by acquiring basic residues near the receptor binding site. They bind more weakly to avian receptor because they lack specific interactions between Asn-186 and Gln-226. In contrast, a double mutant, Δ133/Ile155Thr, isolated in Egypt has greater avidity for human receptor while retaining wild-type avidity for avian receptor. Despite these increases in human receptor binding, none of the mutants prefers human receptor, unlike aerosol transmissible H5N1 viruses. Nevertheless, mutants with high avidity for both human and avian receptors may be intermediates in the evolution of H5N1 viruses that could infect both humans and poultry.

    Keywords: Avian influenza virus; H5N1 influenza virus; Haemagglutinin; Receptor specificity; Receptor binding; Biolayer interferometry; Haemagglutinin crystal structure


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