Research ArticleANTIVIRAL IMMUNITY

IFN-κ suppresses the replication of influenza A viruses through the IFNAR-MAPK-Fos-CHD6 axis

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Science Signaling  07 Apr 2020:
Vol. 13, Issue 626, eaaz3381
DOI: 10.1126/scisignal.aaz3381

IFN-κ protects against influenza A

Virus-infected cells produce type I interferons (IFNs), which protect neighboring cells from infection by stimulating innate defenses. He et al. found that IFN-κ was produced in the lungs of mice early after infection with various influenza A viruses (IAVs). In cultured human lung epithelial cells, IFN-κ inhibited IAV replication by stimulating the IFN receptors IFNAR1 and IFNAR2, and chromodomain helicase DNA binding protein 6 (CHD6) was a key effector of IFN-κ antiviral activity. IFN-κ–mediated induction of CHD6 expression required the kinase p38 MAPK and the transcription factor c-Fos. Pretreating mice with IFN-κ protected them from subsequent lethal influenza challenge, suggesting that IFN-κ therapy may be useful for preventing or treating IAV infection in humans.

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