Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. May activate transcription by complex formation with other transcriptional factors, possibly members of the STAT family. Binds specifically to the IFN-stimulated response element (ISRE) but not to the IRF-1 binding site PRD-I. Shuttles between cytoplasmic and nuclear compartments, with export being the prevailing effect. When activated, IRF3 interaction with CREBBP prevents its export to the cytoplasm. Widely expressed with higher expression in lung, spleen and intestine. Up-regulated by poly I:C. Belongs to the IRF family.