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Epistatic interactions between neuraminidase mutations facilitated the emergence of the oseltamivir-resistant H1N1 influenza viruses

Oseltamivir-resistant H1N1 influenza viruses carrying the H275Y neuraminidase mutation predominated worldwide during the 2007–2009 seasons. While several neuraminidase substitutions were found to be necessary to counteract the adverse effects of H275Y, the order and impact of evolutionary events inv...

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Autores principales: Duan, Susu, Govorkova, Elena A., Bahl, Justin, Zaraket, Hassan, Baranovich, Tatiana, Seiler, Patrick, Prevost, Kristi, Webster, Robert G., Webby, Richard J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197134/
https://www.ncbi.nlm.nih.gov/pubmed/25297528
http://dx.doi.org/10.1038/ncomms6029
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author Duan, Susu
Govorkova, Elena A.
Bahl, Justin
Zaraket, Hassan
Baranovich, Tatiana
Seiler, Patrick
Prevost, Kristi
Webster, Robert G.
Webby, Richard J.
author_facet Duan, Susu
Govorkova, Elena A.
Bahl, Justin
Zaraket, Hassan
Baranovich, Tatiana
Seiler, Patrick
Prevost, Kristi
Webster, Robert G.
Webby, Richard J.
author_sort Duan, Susu
collection PubMed
description Oseltamivir-resistant H1N1 influenza viruses carrying the H275Y neuraminidase mutation predominated worldwide during the 2007–2009 seasons. While several neuraminidase substitutions were found to be necessary to counteract the adverse effects of H275Y, the order and impact of evolutionary events involved remain elusive. Here, we reconstruct H1N1 neuraminidase phylogeny during 1999–2009, estimate the timing and order of crucial amino acid changes, and evaluate their impact on the biological outcome of the H275Y mutation. Of the twelve neuraminidase substitutions that occurred during 1999–2009, five (chronologically, V234M, R222Q, K329E, D344N, H275Y, and D354G) are necessary for maintaining full neuraminidase function in the presence of the H275Y mutation by altering protein accumulation or enzyme affinity/activity. The sequential emergence and cumulative effects of these mutations clearly illustrate a role for epistasis in shaping the emergence and subsequent evolution of a drug-resistant virus population, which can be useful in understanding emergence of novel viral phenotypes of influenza.
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spelling pubmed-41971342015-04-09 Epistatic interactions between neuraminidase mutations facilitated the emergence of the oseltamivir-resistant H1N1 influenza viruses Duan, Susu Govorkova, Elena A. Bahl, Justin Zaraket, Hassan Baranovich, Tatiana Seiler, Patrick Prevost, Kristi Webster, Robert G. Webby, Richard J. Nat Commun Article Oseltamivir-resistant H1N1 influenza viruses carrying the H275Y neuraminidase mutation predominated worldwide during the 2007–2009 seasons. While several neuraminidase substitutions were found to be necessary to counteract the adverse effects of H275Y, the order and impact of evolutionary events involved remain elusive. Here, we reconstruct H1N1 neuraminidase phylogeny during 1999–2009, estimate the timing and order of crucial amino acid changes, and evaluate their impact on the biological outcome of the H275Y mutation. Of the twelve neuraminidase substitutions that occurred during 1999–2009, five (chronologically, V234M, R222Q, K329E, D344N, H275Y, and D354G) are necessary for maintaining full neuraminidase function in the presence of the H275Y mutation by altering protein accumulation or enzyme affinity/activity. The sequential emergence and cumulative effects of these mutations clearly illustrate a role for epistasis in shaping the emergence and subsequent evolution of a drug-resistant virus population, which can be useful in understanding emergence of novel viral phenotypes of influenza. 2014-10-09 /pmc/articles/PMC4197134/ /pubmed/25297528 http://dx.doi.org/10.1038/ncomms6029 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Duan, Susu
Govorkova, Elena A.
Bahl, Justin
Zaraket, Hassan
Baranovich, Tatiana
Seiler, Patrick
Prevost, Kristi
Webster, Robert G.
Webby, Richard J.
Epistatic interactions between neuraminidase mutations facilitated the emergence of the oseltamivir-resistant H1N1 influenza viruses
title Epistatic interactions between neuraminidase mutations facilitated the emergence of the oseltamivir-resistant H1N1 influenza viruses
title_full Epistatic interactions between neuraminidase mutations facilitated the emergence of the oseltamivir-resistant H1N1 influenza viruses
title_fullStr Epistatic interactions between neuraminidase mutations facilitated the emergence of the oseltamivir-resistant H1N1 influenza viruses
title_full_unstemmed Epistatic interactions between neuraminidase mutations facilitated the emergence of the oseltamivir-resistant H1N1 influenza viruses
title_short Epistatic interactions between neuraminidase mutations facilitated the emergence of the oseltamivir-resistant H1N1 influenza viruses
title_sort epistatic interactions between neuraminidase mutations facilitated the emergence of the oseltamivir-resistant h1n1 influenza viruses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197134/
https://www.ncbi.nlm.nih.gov/pubmed/25297528
http://dx.doi.org/10.1038/ncomms6029
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