Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?

A novel, swine-origin influenza H1N1 virus (H1N1pdm) caused the first pandemic of the 21st century. This pandemic, although efficient in transmission, is mild in virulence. This atypical mild pandemic season has raised concerns regarding the potential of this virus to acquire additional virulence ma...

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Autores principales:	Jianqiang Ye, Erin M Sorrell, Yibin Cai, Hongxia Shao, Kemin Xu, Lindomar Pena, Danielle Hickman, Haichen Song, Matthew Angel, Rafael A Medina, Balaji Manicassamy, Adolfo Garcia-Sastre, Daniel R Perez
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ca63743c14db434a86907c256bb755ab
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spelling	oai:doaj.org-article:ca63743c14db434a86907c256bb755ab2021-11-18T06:03:50ZVariations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?1553-73661553-737410.1371/journal.ppat.1001145https://doaj.org/article/ca63743c14db434a86907c256bb755ab2010-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20976194/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374A novel, swine-origin influenza H1N1 virus (H1N1pdm) caused the first pandemic of the 21st century. This pandemic, although efficient in transmission, is mild in virulence. This atypical mild pandemic season has raised concerns regarding the potential of this virus to acquire additional virulence markers either through further adaptation or possibly by immune pressure in the human host. Using the mouse model we generated, within a single round of infection with A/California/04/09/H1N1 (Ca/04), a virus lethal in mice--herein referred to as mouse-adapted Ca/04 (ma-Ca/04). Five amino acid substitutions were found in the genome of ma-Ca/04: 3 in HA (D131E, S186P and A198E), 1 in PA (E298K) and 1 in NP (D101G). Reverse genetics analyses of these mutations indicate that all five mutations from ma-Ca/04 contributed to the lethal phenotype; however, the D131E and S186P mutations--which are also found in the 1918 and seasonal H1N1 viruses-in HA alone were sufficient to confer virulence of Ca/04 in mice. HI assays against H1N1pdm demonstrate that the D131E and S186P mutations caused minor antigenic changes and, likely, affected receptor binding. The rapid selection of ma-Ca/04 in mice suggests that a virus containing this constellation of amino acids might have already been present in Ca/04, likely as minor quasispecies.Jianqiang YeErin M SorrellYibin CaiHongxia ShaoKemin XuLindomar PenaDanielle HickmanHaichen SongMatthew AngelRafael A MedinaBalaji ManicassamyAdolfo Garcia-SastreDaniel R PerezPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 10, p e1001145 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Jianqiang Ye Erin M Sorrell Yibin Cai Hongxia Shao Kemin Xu Lindomar Pena Danielle Hickman Haichen Song Matthew Angel Rafael A Medina Balaji Manicassamy Adolfo Garcia-Sastre Daniel R Perez Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?
description	A novel, swine-origin influenza H1N1 virus (H1N1pdm) caused the first pandemic of the 21st century. This pandemic, although efficient in transmission, is mild in virulence. This atypical mild pandemic season has raised concerns regarding the potential of this virus to acquire additional virulence markers either through further adaptation or possibly by immune pressure in the human host. Using the mouse model we generated, within a single round of infection with A/California/04/09/H1N1 (Ca/04), a virus lethal in mice--herein referred to as mouse-adapted Ca/04 (ma-Ca/04). Five amino acid substitutions were found in the genome of ma-Ca/04: 3 in HA (D131E, S186P and A198E), 1 in PA (E298K) and 1 in NP (D101G). Reverse genetics analyses of these mutations indicate that all five mutations from ma-Ca/04 contributed to the lethal phenotype; however, the D131E and S186P mutations--which are also found in the 1918 and seasonal H1N1 viruses-in HA alone were sufficient to confer virulence of Ca/04 in mice. HI assays against H1N1pdm demonstrate that the D131E and S186P mutations caused minor antigenic changes and, likely, affected receptor binding. The rapid selection of ma-Ca/04 in mice suggests that a virus containing this constellation of amino acids might have already been present in Ca/04, likely as minor quasispecies.
format	article
author	Jianqiang Ye Erin M Sorrell Yibin Cai Hongxia Shao Kemin Xu Lindomar Pena Danielle Hickman Haichen Song Matthew Angel Rafael A Medina Balaji Manicassamy Adolfo Garcia-Sastre Daniel R Perez
author_facet	Jianqiang Ye Erin M Sorrell Yibin Cai Hongxia Shao Kemin Xu Lindomar Pena Danielle Hickman Haichen Song Matthew Angel Rafael A Medina Balaji Manicassamy Adolfo Garcia-Sastre Daniel R Perez
author_sort	Jianqiang Ye
title	Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?
title_short	Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?
title_full	Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?
title_fullStr	Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?
title_full_unstemmed	Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?
title_sort	variations in the hemagglutinin of the 2009 h1n1 pandemic virus: potential for strains with altered virulence phenotype?
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/ca63743c14db434a86907c256bb755ab
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Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype?

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