| Autor: |
Thiele, Swantje, Stanelle-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 |
| Zdroj: |
Cell Reports; April 2020, Vol. 31 Issue: 3 |
| Abstrakt: |
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. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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