Review: Nuclear/Cytoplasmic Localization of IRFs in Response to Viral Infection or Interferon Stimulation

Abstract

Members of the interferon (IFN) regulatory factor (IRFs) family of transcription factors play diverse roles in immunity and cellular response to viral infections. Their biologic effects result from their ability to regulate either constitutive, inducible, or tissue-specific gene expression. All characterized IRFs contain nuclear localization signals that allow their translocation to the nucleus. However, certain IRFs reside in a latent state in the cytoplasm of the cell and only redistribute to the nucleus following an activating trigger. IRF-3 and IRF-9 are examples of IRFs that are regulated by cellular redistribution. These IRFs use distinct mechanisms that regulate nuclear/cytoplasmic localization, and both depend on strong interaction with non-IRF subunits of multimeric transcription complexes. This review compares the activation of IRF-3 and IRF-9 and their respective physiologic impacts.