Transcriptome profiling and protease inhibition experiments identify proteases that activate H3N2 influenza A and influenza B viruses in murine airways
نویسندگان
چکیده
Cleavage of influenza virus hemagglutinin (HA) by host proteases is essential for infectivity. HA most A and B (IAV/IBV) viruses cleaved at a monobasic motif trypsin-like proteases. Previous studies have reported that transmembrane serine protease 2 (TMPRSS2) activation H7N9 H1N1pdm IAV in mice but H3N2 IBV independent TMPRSS2 carried out as-yet-undetermined protease(s). Here, to identify additional H3 IAV- IBV-activating proteases, we used RNA-Seq investigate the repertoire murine lower airway tissues, primary type II alveolar epithelial cells (AECIIs), mouse lung cell line MLE-15. Among 13 candidates identified, TMPRSS4, TMPRSS13, hepsin, prostasin activated vitro. replication was reduced AECIIs from Tmprss2/Tmprss4-deficient compared with WT or Tmprss2-deficient mice, indicating TMPRSS4 involved activation. Multicycle varied sensitivity inhibitors, different, overlapping, sets facilitate cleavages. Interestingly, human hepsin orthologs did not activate H3, they Our results indicate an suggest cleave mice. They further show might contribute differences observed TMPRSS2-independent airways.
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ژورنال
عنوان ژورنال: The FASEB Journal
سال: 2021
ISSN: ['0892-6638', '1530-6860']
DOI: https://doi.org/10.1096/fasebj.2021.35.s1.02714