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

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 hum...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582370/
https://www.ncbi.nlm.nih.gov/pubmed/28694323
http://dx.doi.org/10.15252/emmm.201707726
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author 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
author_facet 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
author_sort de Vries, Robert P
collection PubMed
description 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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spelling pubmed-55823702017-09-06 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 EMBO Mol Med Research Articles 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. John Wiley and Sons Inc. 2017-07-10 2017-09 /pmc/articles/PMC5582370/ /pubmed/28694323 http://dx.doi.org/10.15252/emmm.201707726 Text en © 2017 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
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
A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human‐type receptors
title A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human‐type receptors
title_full A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human‐type receptors
title_fullStr A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human‐type receptors
title_full_unstemmed A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human‐type receptors
title_short A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human‐type receptors
title_sort single mutation in taiwanese h6n1 influenza hemagglutinin switches binding to human‐type receptors
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582370/
https://www.ncbi.nlm.nih.gov/pubmed/28694323
http://dx.doi.org/10.15252/emmm.201707726
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