Functional Evolution of the 2009 Pandemic H1N1 Influenza Virus NS1 and PA in Humans

In 2009, a pandemic H1N1 influenza A virus (IAV) (pH1N1) emerged in the human population from swine causing a pandemic. Importantly, this virus is still circulating in humans seasonally. To analyze the evolution of pH1N1 in humans, we sequenced viral genes encoding proteins inhibiting general gene e...

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Authors: Nogales, Aitor, Martínez-Sobrido, Luis, Chiem, Kevin, Topham, David J., DeDiego, Marta L.
Format: article
Status:Published version
Publication Date:2018
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/346060
Online Access:http://hdl.handle.net/10261/346060
Access Level:Open access
Keyword:NS1
PA-X
Gene expression inhibition
Inflammatory responses
Influenza virus
Innate immunity
Interferon responses
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spelling Functional Evolution of the 2009 Pandemic H1N1 Influenza Virus NS1 and PA in HumansNogales, AitorMartínez-Sobrido, LuisChiem, KevinTopham, David J.DeDiego, Marta L.NS1PA-XGene expression inhibitionInflammatory responsesInfluenza virusInnate immunityInterferon responsesIn 2009, a pandemic H1N1 influenza A virus (IAV) (pH1N1) emerged in the human population from swine causing a pandemic. Importantly, this virus is still circulating in humans seasonally. To analyze the evolution of pH1N1 in humans, we sequenced viral genes encoding proteins inhibiting general gene expression (nonstructural protein 1 [NS1] and PA-X) from circulating seasonal viruses and compared them to the viruses isolated at the origin of the pandemic. Recent pH1N1 viruses contain amino acid changes in the NS1 protein (E55K, L90I, I123V, E125D, K131E, and N205S), as previously described (A. M. Clark, A. Nogales, L. Martinez-Sobrido, D. J. Topham, and M. L. DeDiego, J Virol 91:e00721-17, 2017, https://doi.org/10.1128/JVI.00721-17), and amino acid changes in the PA-X protein (V100I, N204S, R221Q, and L229S). These amino acid differences between early and more recent pH1N1 isolates are responsible for increased NS1-mediated inhibition of host gene expression and decreased PA-X-mediated shutoff, including innate immune response genes. In addition, currently circulating pH1N1 viruses have acquired amino acid changes in the PA protein (V100I, P224S, N321K, I330V, and R362K). A recombinant pH1N1 virus containing PA, PA-X, and NS1 genes from currently circulating viruses is fitter in replication in cultured cells and in mice and is slightly more pathogenic than the original ancestor pH1N1 virus. These results demonstrate the need to monitor the evolution of pH1N1 in humans for mutations in the viral genome that could result in enhanced virulence. Importantly, these results further support our previous findings suggesting that inhibition of global gene expression mediated by NS1 and PA-X proteins is subject to a balance which can determine virus pathogenesis and fitness.This project has been funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Centers of Excellence in Influenza Research and Surveillance (CEIRS) contract no. HHSN272201400005C to D.J.T. and L.M.-S.; with funds from a University of Rochester research award to M.L.D. and A.N.; and with funds from the Comunidad de Madrid, Spain, to M.L.D. (reference no. 2017-T1/BMD-5155).Peer reviewedAmerican Society for MicrobiologyNational Institute of Allergy and Infectious Diseases (US)National Institutes of Health (US)Department of Health and Human Services (US)University of RochesterComunidad de MadridConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/346060reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#2017-T1/BMD-5155https://doi.org/10.1128/jvi.01206-18Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3460602026-05-22T06:33:51Z
dc.title.none.fl_str_mv Functional Evolution of the 2009 Pandemic H1N1 Influenza Virus NS1 and PA in Humans
title Functional Evolution of the 2009 Pandemic H1N1 Influenza Virus NS1 and PA in Humans
spellingShingle Functional Evolution of the 2009 Pandemic H1N1 Influenza Virus NS1 and PA in Humans
Nogales, Aitor
NS1
PA-X
Gene expression inhibition
Inflammatory responses
Influenza virus
Innate immunity
Interferon responses
title_short Functional Evolution of the 2009 Pandemic H1N1 Influenza Virus NS1 and PA in Humans
title_full Functional Evolution of the 2009 Pandemic H1N1 Influenza Virus NS1 and PA in Humans
title_fullStr Functional Evolution of the 2009 Pandemic H1N1 Influenza Virus NS1 and PA in Humans
title_full_unstemmed Functional Evolution of the 2009 Pandemic H1N1 Influenza Virus NS1 and PA in Humans
title_sort Functional Evolution of the 2009 Pandemic H1N1 Influenza Virus NS1 and PA in Humans
dc.creator.none.fl_str_mv Nogales, Aitor
Martínez-Sobrido, Luis
Chiem, Kevin
Topham, David J.
DeDiego, Marta L.
author Nogales, Aitor
author_facet Nogales, Aitor
Martínez-Sobrido, Luis
Chiem, Kevin
Topham, David J.
DeDiego, Marta L.
author_role author
author2 Martínez-Sobrido, Luis
Chiem, Kevin
Topham, David J.
DeDiego, Marta L.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv National Institute of Allergy and Infectious Diseases (US)
National Institutes of Health (US)
Department of Health and Human Services (US)
University of Rochester
Comunidad de Madrid
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv NS1
PA-X
Gene expression inhibition
Inflammatory responses
Influenza virus
Innate immunity
Interferon responses
topic NS1
PA-X
Gene expression inhibition
Inflammatory responses
Influenza virus
Innate immunity
Interferon responses
description In 2009, a pandemic H1N1 influenza A virus (IAV) (pH1N1) emerged in the human population from swine causing a pandemic. Importantly, this virus is still circulating in humans seasonally. To analyze the evolution of pH1N1 in humans, we sequenced viral genes encoding proteins inhibiting general gene expression (nonstructural protein 1 [NS1] and PA-X) from circulating seasonal viruses and compared them to the viruses isolated at the origin of the pandemic. Recent pH1N1 viruses contain amino acid changes in the NS1 protein (E55K, L90I, I123V, E125D, K131E, and N205S), as previously described (A. M. Clark, A. Nogales, L. Martinez-Sobrido, D. J. Topham, and M. L. DeDiego, J Virol 91:e00721-17, 2017, https://doi.org/10.1128/JVI.00721-17), and amino acid changes in the PA-X protein (V100I, N204S, R221Q, and L229S). These amino acid differences between early and more recent pH1N1 isolates are responsible for increased NS1-mediated inhibition of host gene expression and decreased PA-X-mediated shutoff, including innate immune response genes. In addition, currently circulating pH1N1 viruses have acquired amino acid changes in the PA protein (V100I, P224S, N321K, I330V, and R362K). A recombinant pH1N1 virus containing PA, PA-X, and NS1 genes from currently circulating viruses is fitter in replication in cultured cells and in mice and is slightly more pathogenic than the original ancestor pH1N1 virus. These results demonstrate the need to monitor the evolution of pH1N1 in humans for mutations in the viral genome that could result in enhanced virulence. Importantly, these results further support our previous findings suggesting that inhibition of global gene expression mediated by NS1 and PA-X proteins is subject to a balance which can determine virus pathogenesis and fitness.
publishDate 2018
dc.date.none.fl_str_mv 2018
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/346060
url http://hdl.handle.net/10261/346060
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
2017-T1/BMD-5155
https://doi.org/10.1128/jvi.01206-18
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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