Research ArticleImmunology

Unphosphorylated ISGF3 drives constitutive expression of interferon-stimulated genes to protect against viral infections

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Sci. Signal.  25 Apr 2017:
Vol. 10, Issue 476, eaah4248
DOI: 10.1126/scisignal.aah4248

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An interferon-independent antiviral defense

Virally infected cells produce type I interferons (IFNs), which stimulate the phosphorylation and activation of the STAT1 and STAT2 transcription factors. When combined with the transcriptional regulator IRF9, phosphorylated STAT1 and STAT2 form the ISGF3 complex, which drives the expression of IFN-stimulated genes (ISGs) that are important for antiviral immunity. Wang et al. report the formation of an alternative form of ISGF3, U-ISGF3, which drove the expression of ISGs and protected cells from viral infection in the absence of detection of detectable IFN or IFN signaling. In addition to IRF9, U-ISGF3 contained unphosphorylated STAT1 and STAT2. Together, these data suggest that U-ISGF3 drives constitutive expression of ISGs as part of an IFN-independent, antiviral immune response.