Barrier-to-Autointegration Factor 1 Protects against a Basal cGAS-STING Response
Hongming Ma, Wei Qian, Monika Bambousková, Patrick L. Collins, Sofia I. Porter, Andrea K. Byrum, Rong Zhang, Maxim N. Artyomov, Eugene M. Oltz, Nima Mosammaparast, Jonathan J. Miner, Michael Diamond
Abstract
Although the interferon (IFN) signaling pathway is a key host mechanism to restrict infection of a diverse range of viral pathogens, its unrestrained activity either at baseline or in the context of an immune response can result in host cell damage and injury. Here, we used a genome-wide CRISPR-Cas9 screen and identified the DNA binding protein Barrier-to-autointegration factor 1 (Banf1) as a modulator of basal cell-intrinsic immunity. A loss of Banf1 expression resulted in higher level of cytosolic double-stranded DNA at baseline, which triggered IFN-stimulated gene expression via a cGAS-STING-IRF3 axis that did not require type I IFN or STAT1 signaling. Our experiments define a regulatory network in which Banf1 limits basal inflammation by preventing self DNA accumulation in the cytosol.