You are currently viewing the abstract.
View Full TextLog in to view the full text
AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.
More options
Download and print this article for your personal scholarly, research, and educational use.
Buy a single issue of Science for just $15 USD.
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.
Abstract
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-κ 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-κ 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-κ, but not for that of IFN-α or IFN-β. 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-κ protected mice from lethal influenza viral challenge. Together, our findings identify an IFN-κ–specific pathway that constrains influenza A virus and provide evidence that IFN-κ may have potential as a preventative and therapeutic agent against influenza A virus.
This is an article distributed under the terms of the Science Journals Default License.
