The PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase

ABSTRACT The swine-origin H1N1 influenza A virus emerged in early 2009 and caused the first influenza pandemic in 41 years. The virus has spread efficiently to both the Northern and the Southern Hemispheres and has been associated with over 16,000 deaths. Given the virus’s recent zoonotic origin, th...

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Autores principales:	Brett W. Jagger, Matthew J. Memoli, Zong-Mei Sheng, Li Qi, Rachel J. Hrabal, Genevieve L. Allen, Vivien G. Dugan, Ruixue Wang, Paul Digard, John C. Kash, Jeffery K. Taubenberger
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2010
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/939ae4de849e49a7959a16c0be65dc35
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spelling	oai:doaj.org-article:939ae4de849e49a7959a16c0be65dc352021-11-15T15:38:13ZThe PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase10.1128/mBio.00067-102150-7511https://doaj.org/article/939ae4de849e49a7959a16c0be65dc352010-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00067-10https://doaj.org/toc/2150-7511ABSTRACT The swine-origin H1N1 influenza A virus emerged in early 2009 and caused the first influenza pandemic in 41 years. The virus has spread efficiently to both the Northern and the Southern Hemispheres and has been associated with over 16,000 deaths. Given the virus’s recent zoonotic origin, there is concern that the virus could acquire signature mutations associated with the enhanced pathogenicity of previous pandemic viruses or H5N1 viruses with pandemic potential. We tested the hypothesis that mutations in the polymerase PB2 gene at residues 627 and 701 would enhance virulence but found that influenza viruses containing these mutations in the context of the pandemic virus polymerase complex are attenuated in cell culture and mice. IMPORTANCE Influenza A virus (IAV) evolution is characterized by host-specific lineages, and IAVs derived in whole or in part from animal reservoirs have caused pandemics in humans. Because IAVs are known to acquire host-adaptive genome mutations, and since the PB2 gene of the 2009 H1N1 virus is of recent avian derivation, there exists concern that the pathogenicity of the 2009 H1N1 influenza A pandemic virus could be potentiated by acquisition of the host-adaptive PB2-E627K or -D701N mutations, which have been shown to enhance the virulence of other influenza viruses. We present data from a mouse model of influenza infection showing that such mutations do not increase the virulence of viruses containing the 2009 H1N1 viral polymerase.Brett W. JaggerMatthew J. MemoliZong-Mei ShengLi QiRachel J. HrabalGenevieve L. AllenVivien G. DuganRuixue WangPaul DigardJohn C. KashJeffery K. TaubenbergerAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 1, Iss 1 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Brett W. Jagger Matthew J. Memoli Zong-Mei Sheng Li Qi Rachel J. Hrabal Genevieve L. Allen Vivien G. Dugan Ruixue Wang Paul Digard John C. Kash Jeffery K. Taubenberger The PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase
description	ABSTRACT The swine-origin H1N1 influenza A virus emerged in early 2009 and caused the first influenza pandemic in 41 years. The virus has spread efficiently to both the Northern and the Southern Hemispheres and has been associated with over 16,000 deaths. Given the virus’s recent zoonotic origin, there is concern that the virus could acquire signature mutations associated with the enhanced pathogenicity of previous pandemic viruses or H5N1 viruses with pandemic potential. We tested the hypothesis that mutations in the polymerase PB2 gene at residues 627 and 701 would enhance virulence but found that influenza viruses containing these mutations in the context of the pandemic virus polymerase complex are attenuated in cell culture and mice. IMPORTANCE Influenza A virus (IAV) evolution is characterized by host-specific lineages, and IAVs derived in whole or in part from animal reservoirs have caused pandemics in humans. Because IAVs are known to acquire host-adaptive genome mutations, and since the PB2 gene of the 2009 H1N1 virus is of recent avian derivation, there exists concern that the pathogenicity of the 2009 H1N1 influenza A pandemic virus could be potentiated by acquisition of the host-adaptive PB2-E627K or -D701N mutations, which have been shown to enhance the virulence of other influenza viruses. We present data from a mouse model of influenza infection showing that such mutations do not increase the virulence of viruses containing the 2009 H1N1 viral polymerase.
format	article
author	Brett W. Jagger Matthew J. Memoli Zong-Mei Sheng Li Qi Rachel J. Hrabal Genevieve L. Allen Vivien G. Dugan Ruixue Wang Paul Digard John C. Kash Jeffery K. Taubenberger
author_facet	Brett W. Jagger Matthew J. Memoli Zong-Mei Sheng Li Qi Rachel J. Hrabal Genevieve L. Allen Vivien G. Dugan Ruixue Wang Paul Digard John C. Kash Jeffery K. Taubenberger
author_sort	Brett W. Jagger
title	The PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase
title_short	The PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase
title_full	The PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase
title_fullStr	The PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase
title_full_unstemmed	The PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase
title_sort	pb2-e627k mutation attenuates viruses containing the 2009 h1n1 influenza pandemic polymerase
publisher	American Society for Microbiology
publishDate	2010
url	https://doaj.org/article/939ae4de849e49a7959a16c0be65dc35
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The PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase

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