The transcription factor MAFB antagonizes anti-viral responses by blockade of coactivator recruitment to IRF3

Viral infections induce Type I interferons (IFN-α and -β) that recruit unexposed cells in a self-amplifying response. We report that the transcription factor MAFB thwarts auto-amplification by a metastable switch behavior. MAFB acts as a weak positive basal regulator of transcription at the IFN-β promoter through activity at AP-1-like sites. Interferon elicitors recruit the transcription factor IRF3 to the promoter, whereupon MAFB acts as a transcriptional antagonist, impairing the interaction of CREB-binding protein (CBP) with IRF3. Mathematical modeling supports the view that prepositioning of MAFB on the promoter allows the system to respond rapidly to fluctuations in IRF3 activity. Elevated expression of MAFB in human pancreatic islet β-cells might increase cellular vulnerability to viral infections associated with the etiology of type I diabetes.