Virulent PB1-F2 residues: effects on fitness of H1N1 influenza A virus in mice and changes during evolution of human influenza A viruses

Abstract Specific residues of influenza A virus (IAV) PB1-F2 proteins may enhance inflammation or cytotoxicity. In a series of studies, we evaluated the function of these virulence-associated residues in the context of different IAV subtypes in mice. Here, we demonstrate that, as with the previously...

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Autores principales:	Irina V. Alymova, Jonathan A. McCullers, Ram P. Kamal, Peter Vogel, Amanda M. Green, Shane Gansebom, Ian A. York
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6a2f72fbdaf049d9848583d8069f3f83
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spelling	oai:doaj.org-article:6a2f72fbdaf049d9848583d8069f3f832021-12-02T16:07:50ZVirulent PB1-F2 residues: effects on fitness of H1N1 influenza A virus in mice and changes during evolution of human influenza A viruses10.1038/s41598-018-25707-y2045-2322https://doaj.org/article/6a2f72fbdaf049d9848583d8069f3f832018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25707-yhttps://doaj.org/toc/2045-2322Abstract Specific residues of influenza A virus (IAV) PB1-F2 proteins may enhance inflammation or cytotoxicity. In a series of studies, we evaluated the function of these virulence-associated residues in the context of different IAV subtypes in mice. Here, we demonstrate that, as with the previously assessed pandemic 1968 (H3N2) IAV, PB1-F2 inflammatory residues increase the virulence of H1N1 IAV, suggesting that this effect might be a universal feature. Combining both inflammatory and cytotoxic residues in PB1-F2 enhanced virulence further, compared to either motif alone. Residues from these virulent motifs have been present in natural isolates from human seasonal IAV of all subtypes, but there has been a trend toward a gradual reduction in the number of virulent residues over time. However, human IAV of swine and avian origin tend to have more virulent residues than do the human-adapted seasonal strains, raising the possibility that donation of PB1 segments from these zoonotic viruses may increase the severity of some seasonal human strains. Our data suggest the value of surveillance of virulent residues in both human and animal IAV to predict the severity of influenza season.Irina V. AlymovaJonathan A. McCullersRam P. KamalPeter VogelAmanda M. GreenShane GansebomIan A. YorkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Irina V. Alymova Jonathan A. McCullers Ram P. Kamal Peter Vogel Amanda M. Green Shane Gansebom Ian A. York Virulent PB1-F2 residues: effects on fitness of H1N1 influenza A virus in mice and changes during evolution of human influenza A viruses
description	Abstract Specific residues of influenza A virus (IAV) PB1-F2 proteins may enhance inflammation or cytotoxicity. In a series of studies, we evaluated the function of these virulence-associated residues in the context of different IAV subtypes in mice. Here, we demonstrate that, as with the previously assessed pandemic 1968 (H3N2) IAV, PB1-F2 inflammatory residues increase the virulence of H1N1 IAV, suggesting that this effect might be a universal feature. Combining both inflammatory and cytotoxic residues in PB1-F2 enhanced virulence further, compared to either motif alone. Residues from these virulent motifs have been present in natural isolates from human seasonal IAV of all subtypes, but there has been a trend toward a gradual reduction in the number of virulent residues over time. However, human IAV of swine and avian origin tend to have more virulent residues than do the human-adapted seasonal strains, raising the possibility that donation of PB1 segments from these zoonotic viruses may increase the severity of some seasonal human strains. Our data suggest the value of surveillance of virulent residues in both human and animal IAV to predict the severity of influenza season.
format	article
author	Irina V. Alymova Jonathan A. McCullers Ram P. Kamal Peter Vogel Amanda M. Green Shane Gansebom Ian A. York
author_facet	Irina V. Alymova Jonathan A. McCullers Ram P. Kamal Peter Vogel Amanda M. Green Shane Gansebom Ian A. York
author_sort	Irina V. Alymova
title	Virulent PB1-F2 residues: effects on fitness of H1N1 influenza A virus in mice and changes during evolution of human influenza A viruses
title_short	Virulent PB1-F2 residues: effects on fitness of H1N1 influenza A virus in mice and changes during evolution of human influenza A viruses
title_full	Virulent PB1-F2 residues: effects on fitness of H1N1 influenza A virus in mice and changes during evolution of human influenza A viruses
title_fullStr	Virulent PB1-F2 residues: effects on fitness of H1N1 influenza A virus in mice and changes during evolution of human influenza A viruses
title_full_unstemmed	Virulent PB1-F2 residues: effects on fitness of H1N1 influenza A virus in mice and changes during evolution of human influenza A viruses
title_sort	virulent pb1-f2 residues: effects on fitness of h1n1 influenza a virus in mice and changes during evolution of human influenza a viruses
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/6a2f72fbdaf049d9848583d8069f3f83
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Virulent PB1-F2 residues: effects on fitness of H1N1 influenza A virus in mice and changes during evolution of human influenza A viruses

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