Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses

Abstract It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry. We identified this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c...

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Autores principales:	Sehee Park, Jin Il Kim, Ilseob Lee, Joon-Yong Bae, Kirim Yoo, Misun Nam, Juwon Kim, Mee Sook Park, Ki-Joon Song, Jin-Won Song, Sun-Ho Kee, Man-Seong Park
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3693a39062d9445bb2927ce0bb4b9fa5
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spelling	oai:doaj.org-article:3693a39062d9445bb2927ce0bb4b9fa52021-12-02T15:05:28ZAdaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses10.1038/s41598-017-11348-02045-2322https://doaj.org/article/3693a39062d9445bb2927ce0bb4b9fa52017-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-11348-0https://doaj.org/toc/2045-2322Abstract It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry. We identified this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c mice. The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region. To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics. Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice. The increased pathogenicity of these NA stalk mutants was also reproduced in ferrets. In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model. Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.Sehee ParkJin Il KimIlseob LeeJoon-Yong BaeKirim YooMisun NamJuwon KimMee Sook ParkKi-Joon SongJin-Won SongSun-Ho KeeMan-Seong ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sehee Park Jin Il Kim Ilseob Lee Joon-Yong Bae Kirim Yoo Misun Nam Juwon Kim Mee Sook Park Ki-Joon Song Jin-Won Song Sun-Ho Kee Man-Seong Park Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses
description	Abstract It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry. We identified this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c mice. The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region. To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics. Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice. The increased pathogenicity of these NA stalk mutants was also reproduced in ferrets. In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model. Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
format	article
author	Sehee Park Jin Il Kim Ilseob Lee Joon-Yong Bae Kirim Yoo Misun Nam Juwon Kim Mee Sook Park Ki-Joon Song Jin-Won Song Sun-Ho Kee Man-Seong Park
author_facet	Sehee Park Jin Il Kim Ilseob Lee Joon-Yong Bae Kirim Yoo Misun Nam Juwon Kim Mee Sook Park Ki-Joon Song Jin-Won Song Sun-Ho Kee Man-Seong Park
author_sort	Sehee Park
title	Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses
title_short	Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses
title_full	Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses
title_fullStr	Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses
title_full_unstemmed	Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses
title_sort	adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza a viruses
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3693a39062d9445bb2927ce0bb4b9fa5
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Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses

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