Journal
SCIENCE SIGNALING
Volume 13, Issue 626, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.aaz3381
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Funding
- National Science Foundation of China [81430030, 81771704]
- Shanghai Outstanding Academic Leaders Plan [2016-035]
- Shanghai Pujiang Program [19PJ1409100]
- National 13th Five-Year Grand Program on Key Infectious Disease Control and Prevention [2017ZX10304402-002-007, 2018ZX10301403-003]
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Type I interferons (IFNs) are the first line of defense against viral infection. Using a mouse model of influenza A virus infection, we found that IFN-kappa was one of the earliest responding type I IFNs after infection with H9N2, a low-pathogenic avian influenza A virus, whereas this early induction did not occur upon infection with the epidemic-causing H7N9 virus. IFN-kappa efficiently suppressed the replication of various influenza viruses in cultured human lung cells, and chromodomain helicase DNA binding protein 6 (CHD6) was the major effector for the antiviral activity of IFN-kappa, but not for that of IFN-alpha or IFN-beta. The induction of CHD6 required both of the type I IFN receptor subunits IFNAR1 and IFNAR2, the mitogen-activated protein kinase (MAPK) p38, and the transcription factor c-Fos but was independent of signal transducer and activator of transcription 1 (STAT1) activity. In addition, we showed that pretreatment with IFN-kappa protected mice from lethal influenza viral challenge. Together, our findings identify an IFN-kappa-specific pathway that constrains influenza A virus and provide evidence that IFN-kappa may have potential as a preventative and therapeutic agent against influenza A virus.
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