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| Item Type: | Article |
|---|---|
| Title: | Cellular importin-α3 expression dynamics in the lung regulate antiviral response pathways against influenza a virus infection |
| Creators Name: | Thiele, S., Stanelle-Bertram, S., Beck, S., Kouassi, N., Zickler, M., Müller, M., Tuku, B., Resa-Infante, P., van Riel, D., Alawi, M., Günther, T., Rother, F., Hügel, S., Reimering, S., McHardy, A., Grundhoff, A., Brune, W., Osterhaus, A., Bader, M., Hartmann, E. and Gabriel, G. |
| Abstract: | 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. |
| Keywords: | Lung, Influenza, Pneumonia, Immune Sensor, Cytokine Storm, Animals, Mice |
| Source: | Cell Reports |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 31 |
| Number: | 3 |
| Page Range: | 107549 |
| Date: | 21 April 2020 |
| Additional Information: | Erratum in: Cell Rep 43(4):114023 |
| Official Publication: | https://doi.org/10.1016/j.celrep.2020.107549 |
| PubMed: | View item in PubMed |
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