Research ArticleImmunology

STING is an essential mediator of the Ku70-mediated production of IFN-λ1 in response to exogenous DNA

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Sci. Signal.  18 Jul 2017:
Vol. 10, Issue 488, eaah5054
DOI: 10.1126/scisignal.aah5054

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STINGing viruses with IFN-λ1

When cells sense cytosolic DNA, such as occurs during viral infection, they produce type I interferons (IFNs) as part of the antiviral response. Various cytosolic DNA sensors and their downstream effectors stimulate activation of the transcription factor IFN regulatory factor 3 (IRF3) to induce expression of genes encoding type I IFNs. Sui et al. investigated the mechanism by which the DNA protein kinase (DNA-PK) component Ku70, a DNA repair protein, induced production of the type III IFN IFN-λ1 in human cells exposed to cytosolic DNA or infected with the DNA virus HSV-2. Ku70 translocated from the nucleus to the cytosol to interact with the adaptor protein STING, a well-characterized mediator of type I IFN production. However, in the Ku70 pathway, IRF1 and IRF7 were required in addition to IRF3, and type III IFN production was slower than that of type I IFN. Together, these data suggest a role for STING in the late phase of the antiviral IFN response to DNA viruses.