Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic?

ABSTRACT Epidemiologic observations that have been made in the context of the current pandemic influenza virus include a stable virulence phenotype and a lack of propensity to reassort with seasonal strains. In an attempt to determine whether either of these observations could change in the future,...

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Autores principales:	Natalia A. Ilyushina, Mariette F. Ducatez, Jerold E. Rehg, Bindumadhav M. Marathe, Henju Marjuki, Nicolai V. Bovin, Robert G. Webster, Richard J. Webby
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2010
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0986f42f07af412ca8b59429f751480c
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spelling	oai:doaj.org-article:0986f42f07af412ca8b59429f751480c2021-11-15T15:38:17ZDoes Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic?10.1128/mBio.00249-102150-7511https://doaj.org/article/0986f42f07af412ca8b59429f751480c2010-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00249-10https://doaj.org/toc/2150-7511ABSTRACT Epidemiologic observations that have been made in the context of the current pandemic influenza virus include a stable virulence phenotype and a lack of propensity to reassort with seasonal strains. In an attempt to determine whether either of these observations could change in the future, we coinfected differentiated human airway cells with seasonal oseltamivir-resistant A/New Jersey/15/07 and pandemic A/Tennessee/1-560/09 (H1N1) viruses in three ratios (10:90, 50:50, and 90:10) and examined the resulting progeny viruses after 10 sequential passages. When the pandemic virus was initially present at multiplicities of infection equal to or greater than those for the seasonal virus, only pandemic virus genotypes were detected. These adapted pandemic strains did, however, contain two nonsynonymous mutations (hemagglutinin K154Q and polymerase acidic protein L295P) that conferred a more virulent phenotype, both in cell cultures and in ferrets, than their parental strains. The polymerase acidic protein mutation increased polymerase activity at 37°C, and the hemagglutinin change affected binding of the virus to α2,6-sialyl receptors. When the seasonal A/H1N1 virus was initially present in excess, the dominant progeny virus was a reassortant containing the hemagglutinin gene from the seasonal strain and the remaining genes from the pandemic virus. Our study demonstrates that the emergence of an A/H1N1 pandemic strain of higher virulence is possible and that, despite their lack of detection thus far in humans, viable seasonal/pandemic virus reassortants can be generated. IMPORTANCE This report supplies a key piece of information for investigating future evolution scenarios of pandemic A/H1N1 influenza in the human population. We report that the emergence of an A/H1N1 pandemic strain of higher virulence is possible and that, despite their lack of detection thus far in humans, viable seasonal/pandemic virus reassortants can be generated.Natalia A. IlyushinaMariette F. DucatezJerold E. RehgBindumadhav M. MaratheHenju MarjukiNicolai V. BovinRobert G. WebsterRichard J. WebbyAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 1, Iss 5 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Natalia A. Ilyushina Mariette F. Ducatez Jerold E. Rehg Bindumadhav M. Marathe Henju Marjuki Nicolai V. Bovin Robert G. Webster Richard J. Webby Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic?
description	ABSTRACT Epidemiologic observations that have been made in the context of the current pandemic influenza virus include a stable virulence phenotype and a lack of propensity to reassort with seasonal strains. In an attempt to determine whether either of these observations could change in the future, we coinfected differentiated human airway cells with seasonal oseltamivir-resistant A/New Jersey/15/07 and pandemic A/Tennessee/1-560/09 (H1N1) viruses in three ratios (10:90, 50:50, and 90:10) and examined the resulting progeny viruses after 10 sequential passages. When the pandemic virus was initially present at multiplicities of infection equal to or greater than those for the seasonal virus, only pandemic virus genotypes were detected. These adapted pandemic strains did, however, contain two nonsynonymous mutations (hemagglutinin K154Q and polymerase acidic protein L295P) that conferred a more virulent phenotype, both in cell cultures and in ferrets, than their parental strains. The polymerase acidic protein mutation increased polymerase activity at 37°C, and the hemagglutinin change affected binding of the virus to α2,6-sialyl receptors. When the seasonal A/H1N1 virus was initially present in excess, the dominant progeny virus was a reassortant containing the hemagglutinin gene from the seasonal strain and the remaining genes from the pandemic virus. Our study demonstrates that the emergence of an A/H1N1 pandemic strain of higher virulence is possible and that, despite their lack of detection thus far in humans, viable seasonal/pandemic virus reassortants can be generated. IMPORTANCE This report supplies a key piece of information for investigating future evolution scenarios of pandemic A/H1N1 influenza in the human population. We report that the emergence of an A/H1N1 pandemic strain of higher virulence is possible and that, despite their lack of detection thus far in humans, viable seasonal/pandemic virus reassortants can be generated.
format	article
author	Natalia A. Ilyushina Mariette F. Ducatez Jerold E. Rehg Bindumadhav M. Marathe Henju Marjuki Nicolai V. Bovin Robert G. Webster Richard J. Webby
author_facet	Natalia A. Ilyushina Mariette F. Ducatez Jerold E. Rehg Bindumadhav M. Marathe Henju Marjuki Nicolai V. Bovin Robert G. Webster Richard J. Webby
author_sort	Natalia A. Ilyushina
title	Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic?
title_short	Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic?
title_full	Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic?
title_fullStr	Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic?
title_full_unstemmed	Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic?
title_sort	does pandemic a/h1n1 virus have the potential to become more pathogenic?
publisher	American Society for Microbiology
publishDate	2010
url	https://doaj.org/article/0986f42f07af412ca8b59429f751480c
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Does Pandemic A/H1N1 Virus Have the Potential To Become More Pathogenic?

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