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Receptor binding by a ferret-transmissible H5 avian influenza virus.
Nature. 2013 May 16; 497(7449):392-6.Nat

Abstract

Cell-surface-receptor binding by influenza viruses is a key determinant of their transmissibility, both from avian and animal species to humans as well as from human to human. Highly pathogenic avian H5N1 viruses that are a threat to public health have been observed to acquire affinity for human receptors, and transmissible-mutant-selection experiments have identified a virus that is transmissible in ferrets, the generally accepted experimental model for influenza in humans. Here, our quantitative biophysical measurements of the receptor-binding properties of haemagglutinin (HA) from the transmissible mutant indicate a small increase in affinity for human receptor and a marked decrease in affinity for avian receptor. From analysis of virus and HA binding data we have derived an algorithm that predicts virus avidity from the affinity of individual HA-receptor interactions. It reveals that the transmissible-mutant virus has a 200-fold preference for binding human over avian receptors. The crystal structure of the transmissible-mutant HA in complex with receptor analogues shows that it has acquired the ability to bind human receptor in the same folded-back conformation as seen for HA from the 1918, 1957 (ref. 4), 1968 (ref. 5) and 2009 (ref. 6) pandemic viruses. This binding mode is substantially different from that by which non-transmissible wild-type H5 virus HA binds human receptor. The structure of the complex also explains how the change in preference from avian to human receptors arises from the Gln226Leu substitution, which facilitates binding to human receptor but restricts binding to avian receptor. Both features probably contribute to the acquisition of transmissibility by this mutant virus.

Authors+Show Affiliations

MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23615615

Citation

Xiong, Xiaoli, et al. "Receptor Binding By a Ferret-transmissible H5 Avian Influenza Virus." Nature, vol. 497, no. 7449, 2013, pp. 392-6.
Xiong X, Coombs PJ, Martin SR, et al. Receptor binding by a ferret-transmissible H5 avian influenza virus. Nature. 2013;497(7449):392-6.
Xiong, X., Coombs, P. J., Martin, S. R., Liu, J., Xiao, H., McCauley, J. W., Locher, K., Walker, P. A., Collins, P. J., Kawaoka, Y., Skehel, J. J., & Gamblin, S. J. (2013). Receptor binding by a ferret-transmissible H5 avian influenza virus. Nature, 497(7449), 392-6. https://doi.org/10.1038/nature12144
Xiong X, et al. Receptor Binding By a Ferret-transmissible H5 Avian Influenza Virus. Nature. 2013 May 16;497(7449):392-6. PubMed PMID: 23615615.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Receptor binding by a ferret-transmissible H5 avian influenza virus. AU - Xiong,Xiaoli, AU - Coombs,Peter J, AU - Martin,Stephen R, AU - Liu,Junfeng, AU - Xiao,Haixia, AU - McCauley,John W, AU - Locher,Kathrin, AU - Walker,Philip A, AU - Collins,Patrick J, AU - Kawaoka,Yoshihiro, AU - Skehel,John J, AU - Gamblin,Steven J, Y1 - 2013/04/24/ PY - 2012/12/07/received PY - 2013/04/05/accepted PY - 2013/4/26/entrez PY - 2013/4/26/pubmed PY - 2013/6/5/medline SP - 392 EP - 6 JF - Nature JO - Nature VL - 497 IS - 7449 N2 - Cell-surface-receptor binding by influenza viruses is a key determinant of their transmissibility, both from avian and animal species to humans as well as from human to human. Highly pathogenic avian H5N1 viruses that are a threat to public health have been observed to acquire affinity for human receptors, and transmissible-mutant-selection experiments have identified a virus that is transmissible in ferrets, the generally accepted experimental model for influenza in humans. Here, our quantitative biophysical measurements of the receptor-binding properties of haemagglutinin (HA) from the transmissible mutant indicate a small increase in affinity for human receptor and a marked decrease in affinity for avian receptor. From analysis of virus and HA binding data we have derived an algorithm that predicts virus avidity from the affinity of individual HA-receptor interactions. It reveals that the transmissible-mutant virus has a 200-fold preference for binding human over avian receptors. The crystal structure of the transmissible-mutant HA in complex with receptor analogues shows that it has acquired the ability to bind human receptor in the same folded-back conformation as seen for HA from the 1918, 1957 (ref. 4), 1968 (ref. 5) and 2009 (ref. 6) pandemic viruses. This binding mode is substantially different from that by which non-transmissible wild-type H5 virus HA binds human receptor. The structure of the complex also explains how the change in preference from avian to human receptors arises from the Gln226Leu substitution, which facilitates binding to human receptor but restricts binding to avian receptor. Both features probably contribute to the acquisition of transmissibility by this mutant virus. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/23615615/Receptor_binding_by_a_ferret_transmissible_H5_avian_influenza_virus_ L2 - https://doi.org/10.1038/nature12144 DB - PRIME DP - Unbound Medicine ER -