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Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility

Without baseline human immunity to the emergent avian influenza A(H7N9) virus, neuraminidase inhibitors are vital for controlling viral replication in severe infections. An amino acid change in the viral neuraminidase associated with drug resistance, NA-R292K (N2 numbering), has been found in some H...

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Autores principales: Hai, Rong, Schmolke, Mirco, Leyva-Grado, Victor H., Thangavel, Rajagowthamee R., Margine, Irina, Jaffe, Eric L., Krammer, Florian, Solórzano, Alicia, García-Sastre, Adolfo, Palese, Peter, Bouvier, Nicole M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863970/
https://www.ncbi.nlm.nih.gov/pubmed/24326875
http://dx.doi.org/10.1038/ncomms3854
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author Hai, Rong
Schmolke, Mirco
Leyva-Grado, Victor H.
Thangavel, Rajagowthamee R.
Margine, Irina
Jaffe, Eric L.
Krammer, Florian
Solórzano, Alicia
García-Sastre, Adolfo
Palese, Peter
Bouvier, Nicole M.
author_facet Hai, Rong
Schmolke, Mirco
Leyva-Grado, Victor H.
Thangavel, Rajagowthamee R.
Margine, Irina
Jaffe, Eric L.
Krammer, Florian
Solórzano, Alicia
García-Sastre, Adolfo
Palese, Peter
Bouvier, Nicole M.
author_sort Hai, Rong
collection PubMed
description Without baseline human immunity to the emergent avian influenza A(H7N9) virus, neuraminidase inhibitors are vital for controlling viral replication in severe infections. An amino acid change in the viral neuraminidase associated with drug resistance, NA-R292K (N2 numbering), has been found in some H7N9 clinical isolates. Here we assess the impact of the NA-R292K substitution on antiviral sensitivity and viral replication, pathogenicity and transmissibility of H7N9 viruses. Our data indicate that an H7N9 isolate encoding the NA-R292K substitution is highly resistant to oseltamivir and peramivir and partially resistant to zanamivir. Furthermore, H7N9 reassortants with and without the resistance mutation demonstrate comparable viral replication in primary human respiratory cells, virulence in mice and transmissibility in guinea pigs. Thus, in stark contrast to oseltamivir-resistant seasonal influenza A(H3N2) viruses, H7N9 virus replication and pathogenicity in these models are not substantially altered by the acquisition of high-level oseltamivir resistance due to the NA-R292K mutation.
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spelling pubmed-38639702013-12-20 Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility Hai, Rong Schmolke, Mirco Leyva-Grado, Victor H. Thangavel, Rajagowthamee R. Margine, Irina Jaffe, Eric L. Krammer, Florian Solórzano, Alicia García-Sastre, Adolfo Palese, Peter Bouvier, Nicole M. Nat Commun Article Without baseline human immunity to the emergent avian influenza A(H7N9) virus, neuraminidase inhibitors are vital for controlling viral replication in severe infections. An amino acid change in the viral neuraminidase associated with drug resistance, NA-R292K (N2 numbering), has been found in some H7N9 clinical isolates. Here we assess the impact of the NA-R292K substitution on antiviral sensitivity and viral replication, pathogenicity and transmissibility of H7N9 viruses. Our data indicate that an H7N9 isolate encoding the NA-R292K substitution is highly resistant to oseltamivir and peramivir and partially resistant to zanamivir. Furthermore, H7N9 reassortants with and without the resistance mutation demonstrate comparable viral replication in primary human respiratory cells, virulence in mice and transmissibility in guinea pigs. Thus, in stark contrast to oseltamivir-resistant seasonal influenza A(H3N2) viruses, H7N9 virus replication and pathogenicity in these models are not substantially altered by the acquisition of high-level oseltamivir resistance due to the NA-R292K mutation. Nature Pub. Group 2013-12-10 /pmc/articles/PMC3863970/ /pubmed/24326875 http://dx.doi.org/10.1038/ncomms3854 Text en Copyright © 2013, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Article
Hai, Rong
Schmolke, Mirco
Leyva-Grado, Victor H.
Thangavel, Rajagowthamee R.
Margine, Irina
Jaffe, Eric L.
Krammer, Florian
Solórzano, Alicia
García-Sastre, Adolfo
Palese, Peter
Bouvier, Nicole M.
Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility
title Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility
title_full Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility
title_fullStr Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility
title_full_unstemmed Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility
title_short Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility
title_sort influenza a(h7n9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863970/
https://www.ncbi.nlm.nih.gov/pubmed/24326875
http://dx.doi.org/10.1038/ncomms3854
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