Three mutations switch H7N9 influenza to human-type receptor specificity

Robert P de Vries; Wenjie Peng; Oliver C Grant; Andrew J Thompson; Xueyong Zhu; Kim M Bouwman; Alba T Torrents de la Pena; Marielle J van Breemen; Iresha N Ambepitiya Wickramasinghe; Cornelis A M de Haan; Wenli Yu; Ryan McBride; Rogier W Sanders; Robert J Woods; Monique H Verheije; Ian A Wilson; James C Paulson

doi:10.1371/journal.ppat.1006390

Three mutations switch H7N9 influenza to human-type receptor specificity

PLoS Pathog. 2017 Jun 15;13(6):e1006390. doi: 10.1371/journal.ppat.1006390. eCollection 2017 Jun.

Authors

Robert P de Vries^{1

2}, Wenjie Peng¹, Oliver C Grant³, Andrew J Thompson¹, Xueyong Zhu⁴, Kim M Bouwman⁵, Alba T Torrents de la Pena⁶, Marielle J van Breemen⁶, Iresha N Ambepitiya Wickramasinghe⁵, Cornelis A M de Haan⁷, Wenli Yu⁴, Ryan McBride¹, Rogier W Sanders^{6

8}, Robert J Woods³, Monique H Verheije⁵, Ian A Wilson^{4

9}, James C Paulson¹

Affiliations

¹ Departments of Molecular Medicine, & Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States of America.
² Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, CG Utrecht, The Netherlands.
³ Complex Carbohydrate Research Center, University of Georgia, Athens, GA, United States of America.
⁴ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, United States of America.
⁵ Pathology Division, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, CL Utrecht, The Netherlands.
⁶ Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, AZ Amsterdam, The Netherlands.
⁷ Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1,CL Utrecht, The Netherlands.
⁸ Department of Microbiology and Immunology, Weil Medical College of Cornell University, New York, NY, United States of America.
⁹ Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, United States of America.

Abstract

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.

MeSH terms

Amino Acid Sequence
Animals
Hemagglutinin Glycoproteins, Influenza Virus / chemistry
Hemagglutinin Glycoproteins, Influenza Virus / genetics*
Hemagglutinin Glycoproteins, Influenza Virus / metabolism
Host Specificity
Humans
Influenza A Virus, H3N2 Subtype / chemistry
Influenza A Virus, H3N2 Subtype / genetics
Influenza A Virus, H3N2 Subtype / metabolism
Influenza A Virus, H7N9 Subtype / chemistry
Influenza A Virus, H7N9 Subtype / genetics*
Influenza A Virus, H7N9 Subtype / metabolism
Influenza in Birds / genetics
Influenza in Birds / metabolism
Influenza in Birds / virology*
Influenza, Human / genetics
Influenza, Human / metabolism
Influenza, Human / virology*
Molecular Sequence Data
Mutation
Poultry
Poultry Diseases / genetics
Poultry Diseases / metabolism
Poultry Diseases / virology*
Protein Binding
Receptors, Virus / genetics
Receptors, Virus / metabolism
Sequence Alignment

Substances

Hemagglutinin Glycoproteins, Influenza Virus
Receptors, Virus
hemagglutinin, avian influenza A virus

Abstract

MeSH terms

Substances

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