Three mutations switch H7N9 influenza to human-type receptor specificity

PLoS Pathogens

Andrew J. Thompson¹  Ian A. Wilson¹  Wenjie Peng²  Kim M. Bouwman³  Ryan McBride³  Marielle J. van Breemen⁴  Robert J. Woods⁴  Iresha N. Ambepitiya Wickramasinghe⁴  Monique H. Verheije⁵  Robert P. de Vries⁶  Rogier W. Sanders⁶  Oliver C. Grant⁶  Xueyong Zhu⁶  James C. Paulson⁷  Alba T. Torrents de la Pena⁷  Cornelis A. M. de Haan⁷  Wenli Yu⁸ 

[1] Complex Carbohydrate Research Center, University of Georgia, Athens, GA, United States of America;Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, CG Utrecht, The Netherlands;Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, United States of America;Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, AZ Amsterdam, The Netherlands;Department of Microbiology and Immunology, Weil Medical College of Cornell University, New York, NY, United States of America;Departments of Molecular Medicine, & Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States of America;Pathology Division, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, CL Utrecht, The Netherlands;Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1,CL Utrecht, The Netherlands

关键词: Receptor binding assays;    H7N9;    Microbial mutation;    Trachea;    Chickens;    H1N1;    H5N1;    Influenza A virus;   

DOI  :  10.1371/journal.ppat.1006390

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The avian H7N9 influenza outbreak in 2013 resulted from an unprecedented incidence of influenza transmission to humans from infected poultry. The majority of human H7N9 isolates contained a hemagglutinin (HA) mutation (Q226L) that has previously been associated with a switch in receptor specificity from avian-type (NeuAcα2-3Gal) to human-type (NeuAcα2-6Gal), as documented for the avian progenitors of the 1957 (H2N2) and 1968 (H3N2) human influenza pandemic viruses. While this raised concern that the H7N9 virus was adapting to humans, the mutation was not sufficient to switch the receptor specificity of H7N9, and has not resulted in sustained transmission in humans. To determine if the H7 HA was capable of acquiring human-type receptor specificity, we conducted mutation analyses. Remarkably, three amino acid mutations conferred a switch in specificity for human-type receptors that resembled the specificity of the 2009 human H1 pandemic virus, and promoted binding to human trachea epithelial cells.

【 授权许可】

CC BY