Cellular Importin-α3 Expression Dynamics in the Lung Regulate Antiviral Response Pathways against Influenza A Virus Infection.
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Authors
Thiele, SwantjeStanelle-Bertram, Stephanie
Beck, Sebastian
Kouassi, Nancy Mounogou
Zickler, Martin
Müller, Martin
Tuku, Berfin
Resa-Infante, Patricia
van Riel, Debby
Alawi, Malik
Günther, Thomas
Rother, Franziska
Hügel, Stefanie
Reimering, Susanne
McHardy, Alice
Grundhoff, Adam
Brune, Wolfram
Osterhaus, Albert
Bader, Michael
Hartmann, Enno
Gabriel, Gülsah
Metadata
Show full item recordAbstract
Importin-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.Citation
Cell Rep. 2020 Apr 21;31(3):107549. doi: 10.1016/j.celrep.2020.107549.Affiliation
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.Publisher
Elsevier(Cell Press)Journal
Cell reportsPubMed ID
32320654Type
ArticleLanguage
enEISSN
2211-1247ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2020.107549
Scopus Count
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