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Changes in the hemagglutinin of H5N1 viruses during human infection--influence on receptor binding.
Virology. 2013 Dec; 447(1-2):326-37.V

Abstract

As avian influenza A(H5N1) viruses continue to circulate in Asia and Africa, global concerns of an imminent pandemic persist. Recent experimental studies suggest that efficient transmission between humans of current H5N1 viruses only requires a few genetic changes. An essential step is alteration of the virus hemagglutinin from preferential binding to avian receptors for the recognition of human receptors present in the upper airway. We have identified receptor-binding changes which emerged during H5N1 infection of humans, due to single amino acid substitutions, Ala134Val and Ile151Phe, in the hemagglutinin. Detailed biological, receptor-binding, and structural analyses revealed reduced binding of the mutated viruses to avian-like receptors, but without commensurate increased binding to the human-like receptors investigated, possibly reflecting a receptor-binding phenotype intermediate in adaptation to more human-like characteristics. These observations emphasize that evolution in nature of avian H5N1 viruses to efficient binding of human receptors is a complex multistep process.

Authors+Show Affiliations

Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.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 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 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, N.I.H., Intramural

Language

eng

PubMed ID

24050651

Citation

Crusat, Martin, et al. "Changes in the Hemagglutinin of H5N1 Viruses During Human Infection--influence On Receptor Binding." Virology, vol. 447, no. 1-2, 2013, pp. 326-37.
Crusat M, Liu J, Palma AS, et al. Changes in the hemagglutinin of H5N1 viruses during human infection--influence on receptor binding. Virology. 2013;447(1-2):326-37.
Crusat, M., Liu, J., Palma, A. S., Childs, R. A., Liu, Y., Wharton, S. A., Lin, Y. P., Coombs, P. J., Martin, S. R., Matrosovich, M., Chen, Z., Stevens, D. J., Hien, V. M., Thanh, T. T., Nhu, l. e. . N. T., Nguyet, L. A., Ha, d. o. . Q., van Doorn, H. R., Hien, T. T., ... Feizi, T. (2013). Changes in the hemagglutinin of H5N1 viruses during human infection--influence on receptor binding. Virology, 447(1-2), 326-37. https://doi.org/10.1016/j.virol.2013.08.010
Crusat M, et al. Changes in the Hemagglutinin of H5N1 Viruses During Human Infection--influence On Receptor Binding. Virology. 2013;447(1-2):326-37. PubMed PMID: 24050651.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in the hemagglutinin of H5N1 viruses during human infection--influence on receptor binding. AU - Crusat,Martin, AU - Liu,Junfeng, AU - Palma,Angelina S, AU - Childs,Robert A, AU - Liu,Yan, AU - Wharton,Stephen A, AU - Lin,Yi Pu, AU - Coombs,Peter J, AU - Martin,Stephen R, AU - Matrosovich,Mikhail, AU - Chen,Zi, AU - Stevens,David J, AU - Hien,Vo Minh, AU - Thanh,Tran Tan, AU - Nhu,Le Nguyen Truc, AU - Nguyet,Lam Anh, AU - Ha,Do Quang, AU - van Doorn,H Rogier, AU - Hien,Tran Tinh, AU - Conradt,Harald S, AU - Kiso,Makoto, AU - Gamblin,Steve J, AU - Chai,Wengang, AU - Skehel,John J, AU - Hay,Alan J, AU - Farrar,Jeremy, AU - de Jong,Menno D, AU - Feizi,Ten, Y1 - 2013/09/17/ PY - 2013/06/21/received PY - 2013/08/06/revised PY - 2013/08/12/accepted PY - 2013/9/21/entrez PY - 2013/9/21/pubmed PY - 2014/1/3/medline KW - Biolayer interferometry KW - Carbohydrate microarray KW - H5N1 influenza infection KW - Hemagglutination assays KW - Hemagglutinin KW - Hemagglutinin X-ray crystal structure KW - Pyrosequencing KW - Receptor binding KW - Receptor specificity KW - Synthetic sialylglycopolymers SP - 326 EP - 37 JF - Virology JO - Virology VL - 447 IS - 1-2 N2 - As avian influenza A(H5N1) viruses continue to circulate in Asia and Africa, global concerns of an imminent pandemic persist. Recent experimental studies suggest that efficient transmission between humans of current H5N1 viruses only requires a few genetic changes. An essential step is alteration of the virus hemagglutinin from preferential binding to avian receptors for the recognition of human receptors present in the upper airway. We have identified receptor-binding changes which emerged during H5N1 infection of humans, due to single amino acid substitutions, Ala134Val and Ile151Phe, in the hemagglutinin. Detailed biological, receptor-binding, and structural analyses revealed reduced binding of the mutated viruses to avian-like receptors, but without commensurate increased binding to the human-like receptors investigated, possibly reflecting a receptor-binding phenotype intermediate in adaptation to more human-like characteristics. These observations emphasize that evolution in nature of avian H5N1 viruses to efficient binding of human receptors is a complex multistep process. SN - 1096-0341 UR - https://www.unboundmedicine.com/medline/citation/24050651/Changes_in_the_hemagglutinin_of_H5N1_viruses_during_human_infection__influence_on_receptor_binding_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(13)00481-9 DB - PRIME DP - Unbound Medicine ER -