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Cellular Importin-α3 Expression Dynamics in the Lung Regulate Antiviral Response Pathways against Influenza A Virus Infection

Cell Rep . 2020-04; 
Thiele S, Stanelle-Bertram S, Beck S, Kouassi NM, 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, Gabriel G
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Peptide Synthesis Counterstaining was performed with hematoxylin. Since the importin-α7 antibody, cross-reacts with importin-α5, lung tissues of mice with a deletion of either the importin-α5 or the -α7 gene were additionally used as controls (data not shown). To exclude false-positive staining due to cross-reactivity of the antibodies, FFPE thin sections were additionally stained using importin-α isoform-specific blocking peptides for importin-α1 (aa518-529, QVQDGAPGTFNF, GenScript), importin-α3 (aa509-521, NSSANVPTEGFQF, Abcam, #ab23144), importin-α5 (aa3-16, TPGKENFRLKSYKN, GenScript) and importin-α7 (aa3-12, MASPGKDNYR; aa526-536, PEAPMEGFQL, GenScript) in different concentrations (0.2 μg/ml, 2 μg/ml, and 20 μg/ml) (Table S5).  Get A Quote

摘要

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 polyme... More

关键词

cytokine storm; immune sensor; influenza; lung; pneumonia