Functional Characterization and Direct Comparison of Influenza A, B, C, and D NS1 Proteins in vitro and in vivo

© 2019 Nogales, Aydillo, Ávila-Pérez, Escalera, Chiem, Cadagan, DeDiego, Li, García-Sastre and Martínez-Sobrido.

Detalhes bibliográficos
Autores: Nogales, Aitor, Aydillo, Teresa, Ávila-Pérez, Ginés, Escalera, Alba, Chiem, Kevin, Cadagan, Richard, DeDiego, Marta L., Li, Feng, García-Sastre, Adolfo, Martínez-Sobrido, Luis
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/240360
Acesso em linha:http://hdl.handle.net/10261/240360
Access Level:acceso abierto
Palavra-chave:Influenza A virus
Influenza B virus (IBV)
Influenza C virus (ICV)
Influenza D virus (IDV)
Non-structural protein 1 (NS1)
Signal transducer and activator of transcription 2 (STAT2)
Innate immunity
Interferon (IFN)
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spelling Functional Characterization and Direct Comparison of Influenza A, B, C, and D NS1 Proteins in vitro and in vivoNogales, AitorAydillo, TeresaÁvila-Pérez, GinésEscalera, AlbaChiem, KevinCadagan, RichardDeDiego, Marta L.Li, FengGarcía-Sastre, AdolfoMartínez-Sobrido, LuisInfluenza A virusInfluenza B virus (IBV)Influenza C virus (ICV)Influenza D virus (IDV)Non-structural protein 1 (NS1)Signal transducer and activator of transcription 2 (STAT2)Innate immunityInterferon (IFN)© 2019 Nogales, Aydillo, Ávila-Pérez, Escalera, Chiem, Cadagan, DeDiego, Li, García-Sastre and Martínez-Sobrido.Influenza viruses are important pathogens that affect multiple animal species, including humans. There are four types of influenza viruses: A, B, C, and D (IAV, IBV, ICV, and IDV, respectively). IAV and IBV are currently circulating in humans and are responsible of seasonal epidemics (IAV and IBV) and occasional pandemics (IAV). ICV is known to cause mild infections in humans and pigs, while the recently identified IDV primarily affect cattle and pigs. Influenza non-structural protein 1 (NS1) is a multifunctional protein encoded by the NS segment in all influenza types. The main function of NS1 is to counteract the host antiviral defense, including the production of interferon (IFN) and IFN-stimulated genes (ISGs), and therefore is considered an important viral pathogenic factor. Despite of homologous functions, the NS1 protein from the diverse influenza types share little amino acid sequence identity, suggesting possible differences in their mechanism(s) of action, interaction(s) with host factors, and contribution to viral replication and/or pathogenesis. In addition, although the NS1 protein of IAV, IBV and, to some extent ICV, have been previously studied, it is unclear if IDV NS1 has similar properties. Using an approach that allow us to express NS1 independently of the nuclear export protein from the viral NS segment, we have generated recombinant IAV expressing IAV, IBV, ICV, and IDV NS1 proteins. Although recombinant viruses expressing heterotypic (IBV, ICV, and IDV) NS1 proteins were able to replicate similarly in canine MDCK cells, their viral fitness was impaired in human A549 cells and they were highly attenuated in vivo. Our data suggest that despite the similarities to effectively counteract innate immune responses in vitro, the NS1 proteins of IBV, ICV, or IDV do not fully complement the functions of IAV NS1, resulting in deficient viral replication and pathogenesis in vivo.This research was partially funded by the New York Influenza Center of Excellence (NYICE), a member of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services, Centers of Excellence for Influenza Research and Surveillance (CEIRS) Contract No. HHSN272201400005C (NYICE); by the Department of Defense (DoD) Peer Reviewed Medical Research Program (PRMRP) grant W81XWH-18-1-0460 to LM-S; by the NIH R01AI141889 to FL; and by the Center for Research in Influenza Pathogenesis (CRIP, CEIRS Contract No. HHSN272201400008C to AG-S).Frontiers MediaCenters of Excellence for Influenza Research and Surveillance (US)National Institute of Allergy and Infectious Diseases (US)National Institutes of Health (US)Centers of Excellence for Influenza Research and Surveillance (US)Department of Defense (US)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120192021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/240360reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3389/fmicb.2019.02862Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2403602026-05-22T06:33:51Z
dc.title.none.fl_str_mv Functional Characterization and Direct Comparison of Influenza A, B, C, and D NS1 Proteins in vitro and in vivo
title Functional Characterization and Direct Comparison of Influenza A, B, C, and D NS1 Proteins in vitro and in vivo
spellingShingle Functional Characterization and Direct Comparison of Influenza A, B, C, and D NS1 Proteins in vitro and in vivo
Nogales, Aitor
Influenza A virus
Influenza B virus (IBV)
Influenza C virus (ICV)
Influenza D virus (IDV)
Non-structural protein 1 (NS1)
Signal transducer and activator of transcription 2 (STAT2)
Innate immunity
Interferon (IFN)
title_short Functional Characterization and Direct Comparison of Influenza A, B, C, and D NS1 Proteins in vitro and in vivo
title_full Functional Characterization and Direct Comparison of Influenza A, B, C, and D NS1 Proteins in vitro and in vivo
title_fullStr Functional Characterization and Direct Comparison of Influenza A, B, C, and D NS1 Proteins in vitro and in vivo
title_full_unstemmed Functional Characterization and Direct Comparison of Influenza A, B, C, and D NS1 Proteins in vitro and in vivo
title_sort Functional Characterization and Direct Comparison of Influenza A, B, C, and D NS1 Proteins in vitro and in vivo
dc.creator.none.fl_str_mv Nogales, Aitor
Aydillo, Teresa
Ávila-Pérez, Ginés
Escalera, Alba
Chiem, Kevin
Cadagan, Richard
DeDiego, Marta L.
Li, Feng
García-Sastre, Adolfo
Martínez-Sobrido, Luis
author Nogales, Aitor
author_facet Nogales, Aitor
Aydillo, Teresa
Ávila-Pérez, Ginés
Escalera, Alba
Chiem, Kevin
Cadagan, Richard
DeDiego, Marta L.
Li, Feng
García-Sastre, Adolfo
Martínez-Sobrido, Luis
author_role author
author2 Aydillo, Teresa
Ávila-Pérez, Ginés
Escalera, Alba
Chiem, Kevin
Cadagan, Richard
DeDiego, Marta L.
Li, Feng
García-Sastre, Adolfo
Martínez-Sobrido, Luis
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centers of Excellence for Influenza Research and Surveillance (US)
National Institute of Allergy and Infectious Diseases (US)
National Institutes of Health (US)
Centers of Excellence for Influenza Research and Surveillance (US)
Department of Defense (US)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Influenza A virus
Influenza B virus (IBV)
Influenza C virus (ICV)
Influenza D virus (IDV)
Non-structural protein 1 (NS1)
Signal transducer and activator of transcription 2 (STAT2)
Innate immunity
Interferon (IFN)
topic Influenza A virus
Influenza B virus (IBV)
Influenza C virus (ICV)
Influenza D virus (IDV)
Non-structural protein 1 (NS1)
Signal transducer and activator of transcription 2 (STAT2)
Innate immunity
Interferon (IFN)
description © 2019 Nogales, Aydillo, Ávila-Pérez, Escalera, Chiem, Cadagan, DeDiego, Li, García-Sastre and Martínez-Sobrido.
publishDate 2019
dc.date.none.fl_str_mv 2019
2021
2021
2021
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/10261/240360
url http://hdl.handle.net/10261/240360
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3389/fmicb.2019.02862
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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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score 15,81155

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