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In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses

Newly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population. Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial imp...

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Autores principales: Schmier, Sonja, Mostafa, Ahmed, Haarmann, Thomas, Bannert, Norbert, Ziebuhr, John, Veljkovic, Veljko, Dietrich, Ursula, Pleschka, Stephan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4473683/
https://www.ncbi.nlm.nih.gov/pubmed/26091504
http://dx.doi.org/10.1038/srep11434
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author Schmier, Sonja
Mostafa, Ahmed
Haarmann, Thomas
Bannert, Norbert
Ziebuhr, John
Veljkovic, Veljko
Dietrich, Ursula
Pleschka, Stephan
author_facet Schmier, Sonja
Mostafa, Ahmed
Haarmann, Thomas
Bannert, Norbert
Ziebuhr, John
Veljkovic, Veljko
Dietrich, Ursula
Pleschka, Stephan
author_sort Schmier, Sonja
collection PubMed
description Newly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population. Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial importance for restricting virus transmission and developing appropriate therapeutic and prophylactic strategies including effective vaccines. Often, the pandemic potential of newly emerging IAV is only fully recognized once the virus starts to spread efficiently causing serious disease in humans. Here, we used a novel phylogenetic algorithm based on the informational spectrum method (ISM) to identify potential CPIV by predicting mutations in the viral hemagglutinin (HA) gene that are likely to (differentially) affect critical interactions between the HA protein and target cells from bird and human origin, respectively. Predictions were subsequently validated by generating pseudotyped retrovirus particles and genetically engineered IAV containing these mutations and characterizing potential effects on virus entry and replication in cells expressing human and avian IAV receptors, respectively. Our data suggest that the ISM-based algorithm is suitable to identify CPIV among IAV strains that are circulating in animal hosts and thus may be a new tool for assessing pandemic risks associated with specific strains.
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spelling pubmed-44736832015-07-13 In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses Schmier, Sonja Mostafa, Ahmed Haarmann, Thomas Bannert, Norbert Ziebuhr, John Veljkovic, Veljko Dietrich, Ursula Pleschka, Stephan Sci Rep Article Newly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population. Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial importance for restricting virus transmission and developing appropriate therapeutic and prophylactic strategies including effective vaccines. Often, the pandemic potential of newly emerging IAV is only fully recognized once the virus starts to spread efficiently causing serious disease in humans. Here, we used a novel phylogenetic algorithm based on the informational spectrum method (ISM) to identify potential CPIV by predicting mutations in the viral hemagglutinin (HA) gene that are likely to (differentially) affect critical interactions between the HA protein and target cells from bird and human origin, respectively. Predictions were subsequently validated by generating pseudotyped retrovirus particles and genetically engineered IAV containing these mutations and characterizing potential effects on virus entry and replication in cells expressing human and avian IAV receptors, respectively. Our data suggest that the ISM-based algorithm is suitable to identify CPIV among IAV strains that are circulating in animal hosts and thus may be a new tool for assessing pandemic risks associated with specific strains. Nature Publishing Group 2015-06-19 /pmc/articles/PMC4473683/ /pubmed/26091504 http://dx.doi.org/10.1038/srep11434 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Schmier, Sonja
Mostafa, Ahmed
Haarmann, Thomas
Bannert, Norbert
Ziebuhr, John
Veljkovic, Veljko
Dietrich, Ursula
Pleschka, Stephan
In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses
title In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses
title_full In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses
title_fullStr In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses
title_full_unstemmed In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses
title_short In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses
title_sort in silico prediction and experimental confirmation of ha residues conferring enhanced human receptor specificity of h5n1 influenza a viruses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4473683/
https://www.ncbi.nlm.nih.gov/pubmed/26091504
http://dx.doi.org/10.1038/srep11434
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