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Title: Three mutations switch H7N9 influenza to human-type receptor specificity

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.

Authors:
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Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIHOTHER
OSTI Identifier:
1400283
Resource Type:
Journal Article
Resource Relation:
Journal Name: PLoS Pathogens; Journal Volume: 13; Journal Issue: 6
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats

de Vries, Robert P., Peng, Wenjie, Grant, Oliver C., Thompson, Andrew J., Zhu, Xueyong, Bouwman, Kim M., de la Pena, Alba T. Torrents, van Breemen, Marielle J., Ambepitiya Wickramasinghe, Iresha N., de Haan, Cornelis A. M., Yu, Wenli, McBride, Ryan, Sanders, Rogier W., Woods, Robert J., Verheije, Monique H., Wilson, Ian A., Paulson, James C., and Fernandez-Sesma, Ana. Three mutations switch H7N9 influenza to human-type receptor specificity. United States: N. p., 2017. Web. doi:10.1371/journal.ppat.1006390.
de Vries, Robert P., Peng, Wenjie, Grant, Oliver C., Thompson, Andrew J., Zhu, Xueyong, Bouwman, Kim M., de la Pena, Alba T. Torrents, van Breemen, Marielle J., Ambepitiya Wickramasinghe, Iresha N., de Haan, Cornelis A. M., Yu, Wenli, McBride, Ryan, Sanders, Rogier W., Woods, Robert J., Verheije, Monique H., Wilson, Ian A., Paulson, James C., & Fernandez-Sesma, Ana. Three mutations switch H7N9 influenza to human-type receptor specificity. United States. doi:10.1371/journal.ppat.1006390.
de Vries, Robert P., Peng, Wenjie, Grant, Oliver C., Thompson, Andrew J., Zhu, Xueyong, Bouwman, Kim M., de la Pena, Alba T. Torrents, van Breemen, Marielle J., Ambepitiya Wickramasinghe, Iresha N., de Haan, Cornelis A. M., Yu, Wenli, McBride, Ryan, Sanders, Rogier W., Woods, Robert J., Verheije, Monique H., Wilson, Ian A., Paulson, James C., and Fernandez-Sesma, Ana. Thu . "Three mutations switch H7N9 influenza to human-type receptor specificity". United States. doi:10.1371/journal.ppat.1006390.
@article{osti_1400283,
title = {Three mutations switch H7N9 influenza to human-type receptor specificity},
author = {de Vries, Robert P. and Peng, Wenjie and Grant, Oliver C. and Thompson, Andrew J. and Zhu, Xueyong and Bouwman, Kim M. and de la Pena, Alba T. Torrents and van Breemen, Marielle J. and Ambepitiya Wickramasinghe, Iresha N. and de Haan, Cornelis A. M. and Yu, Wenli and McBride, Ryan and Sanders, Rogier W. and Woods, Robert J. and Verheije, Monique H. and Wilson, Ian A. and Paulson, James C. and Fernandez-Sesma, Ana},
abstractNote = {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.},
doi = {10.1371/journal.ppat.1006390},
journal = {PLoS Pathogens},
number = 6,
volume = 13,
place = {United States},
year = {Thu Jun 15 00:00:00 EDT 2017},
month = {Thu Jun 15 00:00:00 EDT 2017}
}