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dc.contributor.authorThiele, Swantje
dc.contributor.authorStanelle-Bertram, Stephanie
dc.contributor.authorBeck, Sebastian
dc.contributor.authorKouassi, Nancy Mounogou
dc.contributor.authorZickler, Martin
dc.contributor.authorMüller, Martin
dc.contributor.authorTuku, Berfin
dc.contributor.authorResa-Infante, Patricia
dc.contributor.authorvan Riel, Debby
dc.contributor.authorAlawi, Malik
dc.contributor.authorGünther, Thomas
dc.contributor.authorRother, Franziska
dc.contributor.authorHügel, Stefanie
dc.contributor.authorReimering, Susanne
dc.contributor.authorMcHardy, Alice
dc.contributor.authorGrundhoff, Adam
dc.contributor.authorBrune, Wolfram
dc.contributor.authorOsterhaus, Albert
dc.contributor.authorBader, Michael
dc.contributor.authorHartmann, Enno
dc.contributor.authorGabriel, Gülsah
dc.date.accessioned2020-05-12T10:19:46Z
dc.date.available2020-05-12T10:19:46Z
dc.identifier.citationCell Rep. 2020 Apr 21;31(3):107549. doi: 10.1016/j.celrep.2020.107549.en_US
dc.identifier.pmid32320654
dc.identifier.doi10.1016/j.celrep.2020.107549
dc.identifier.urihttp://hdl.handle.net/10033/622259
dc.description.abstractImportin-α adaptor proteins orchestrate dynamic nuclear transport processes involved in cellular homeostasis. Here, we show that importin-α3, one of the main NF-κB transporters, is the most abundantly expressed classical nuclear transport factor in the mammalian respiratory tract. Importin-α3 promoter activity is regulated by TNF-α-induced NF-κB in a concentration-dependent manner. High-level TNF-α-inducing highly pathogenic avian influenza A viruses (HPAIVs) isolated from fatal human cases harboring human-type polymerase signatures (PB2 627K, 701N) significantly downregulate importin-α3 mRNA expression in primary lung cells. Importin-α3 depletion is restored upon back-mutating the HPAIV polymerase into an avian-type signature (PB2 627E, 701D) that can no longer induce high TNF-α levels. Importin-α3-deficient mice show reduced NF-κB-activated antiviral gene expression and increased influenza lethality. Thus, importin-α3 plays a key role in antiviral immunity against influenza. Lifting the bottleneck in importin-α3 availability in the lung might provide a new strategy to combat respiratory virus infections.en_US
dc.language.isoenen_US
dc.publisherElsevier(Cell Press)en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectcytokine stormen_US
dc.subjectimmune sensoren_US
dc.subjectinfluenzaen_US
dc.subjectlungen_US
dc.subjectpneumoniaen_US
dc.titleCellular Importin-α3 Expression Dynamics in the Lung Regulate Antiviral Response Pathways against Influenza A Virus Infection.en_US
dc.typeArticleen_US
dc.identifier.eissn2211-1247
dc.contributor.departmentBRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.en_US
dc.identifier.journalCell reportsen_US
dc.source.volume31
dc.source.issue3
dc.source.beginpage107549
dc.source.endpage
refterms.dateFOA2020-05-12T10:19:46Z
dc.source.journaltitleCell reports
dc.source.countryUnited States


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Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International