A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human‐type receptors

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

doi:10.15252/emmm.201707726

A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human‐type receptors

Journal Article · Mon Jul 10 00:00:00 EDT 2017 · EMBO Molecular Medicine

DOI:https://doi.org/10.15252/emmm.201707726· OSTI ID:1547082

de Vries, Robert P. ^[1]; Tzarum, Netanel ^[2]; Peng, Wenjie ^[3]; Thompson, Andrew J. ^[3]; Ambepitiya Wickramasinghe, Iresha N. ^[4]; de la Pena, Alba T. Torrents ^[5]; van Breemen, Marielle J. ^[5]; Bouwman, Kim M. ^[4]; Zhu, Xueyong ^[2]; McBride, Ryan ^[3]; Yu, Wenli ^[2]; Sanders, Rogier W. ^[6]; Verheije, Monique H. ^[4]; ^[7]; ^[3]

Departments of Molecular Medicine &, Immunology and Microbiology The Scripps Research Institute La Jolla CA USA, Department of Chemical Biology and Drug Discovery Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands
Department of Integrative Structural and Computational Biology The Scripps Research Institute The Scripps Research Institute La Jolla CA USA
Departments of Molecular Medicine &, Immunology and Microbiology The Scripps Research Institute La Jolla CA USA
Pathology Division Department of Pathobiology Faculty of Veterinary Medicine Utrecht University Utrecht The Netherlands
Department of Medical Microbiology Academic Medical Center University of Amsterdam Amsterdam The Netherlands
Department of Medical Microbiology Academic Medical Center University of Amsterdam Amsterdam The Netherlands, Department of Microbiology and Immunology Weil Medical College of Cornell University New York NY USA
Department of Integrative Structural and Computational Biology The Scripps Research Institute The Scripps Research Institute La Jolla CA USA, Skaggs Institute for Chemical Biology The Scripps Research Institute La Jolla CA USA

Abstract

In June 2013, the first case of human infection with an avian H6N1 virus was reported in a Taiwanese woman. Although this was a single non‐fatal case, the virus continues to circulate in Taiwanese poultry. As with any emerging avian virus that infects humans, there is concern that acquisition of human‐type receptor specificity could enable transmission in the human population. Despite mutations in the receptor‐binding pocket of the human H6N1 isolate, it has retained avian‐type (NeuAcα2‐3Gal) receptor specificity. However, we show here that a single nucleotide substitution, resulting in a change from Gly to Asp at position 225 (G225D), completely switches specificity to human‐type (NeuAcα2‐6Gal) receptors. Significantly, G225D H6 loses binding to chicken trachea epithelium and is now able to bind to human tracheal tissue. Structural analysis reveals that Asp225 directly interacts with the penultimate Gal of the human‐type receptor, stabilizing human receptor binding.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: NONE; AC02-06CH11357

OSTI ID:: 1547082

Alternate ID(s):: OSTI ID: 1547083
OSTI ID: 1397296

Journal Information:: EMBO Molecular Medicine, Journal Name: EMBO Molecular Medicine Journal Issue: 9 Vol. 9; ISSN 1757-4676

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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