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

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

doi:10.15252/emmm.201707726

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

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

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	1314-1325
Number of pages	12
Journal	EMBO Journal
Volume	9
Issue number	9
DOIs	https://doi.org/10.15252/emmm.201707726
Publication status	Published - 17 Jul 2017

Keywords

glycan array
hemagglutinin
influenza A virus
sialic acid
X-ray crystallography

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de Vries, R. P., Tzarum, N., Peng, W., Thompson, A. J., Ambepitiya Wickramasinghe, I. N., de la Pena, A. T. T., van Breemen, M. J., Bouwman, K. M., Zhu, X., McBride, R., Yu, W., Sanders, R. W., Verheije, M. H., Wilson, I. A., & Paulson, J. C. (2017). A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors. EMBO Journal, 9(9), 1314-1325. https://doi.org/10.15252/emmm.201707726

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title = "A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors",

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.",

keywords = "glycan array, hemagglutinin, influenza A virus, sialic acid, X-ray crystallography",

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

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de Vries, RP, Tzarum, N, Peng, W, Thompson, AJ, Ambepitiya Wickramasinghe, IN, de la Pena, ATT, van Breemen, MJ, Bouwman, KM, Zhu, X, McBride, R, Yu, W, Sanders, RW, Verheije, MH, Wilson, IA & Paulson, JC 2017, 'A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors', EMBO Journal, vol. 9, no. 9, pp. 1314-1325. https://doi.org/10.15252/emmm.201707726

TY - JOUR

T1 - A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors

AU - de Vries, Robert P

AU - Tzarum, Netanel

AU - Peng, Wenjie

AU - Thompson, Andrew J

AU - Ambepitiya Wickramasinghe, Iresha N

AU - de la Pena, Alba T Torrents

AU - van Breemen, Marielle J

AU - Bouwman, Kim M

AU - Zhu, Xueyong

AU - McBride, Ryan

AU - Yu, Wenli

AU - Sanders, Rogier W

AU - Verheije, Monique H

AU - Wilson, Ian A

AU - Paulson, James C

PY - 2017/7/17

Y1 - 2017/7/17

N2 - 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.

AB - 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.

KW - glycan array

KW - hemagglutinin

KW - influenza A virus

KW - sialic acid

KW - X-ray crystallography

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DO - 10.15252/emmm.201707726

M3 - Article

C2 - 28694323

SN - 0261-4189

VL - 9

SP - 1314

EP - 1325

JO - EMBO Journal

JF - EMBO Journal

IS - 9

ER -

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

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Keywords

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