Interferon regulatory factors

Protein family

Interferon regulatory factors (IRF) are proteins which regulate transcription of interferons (see regulation of gene expression). Interferon regulatory factors contain a conserved N terminal region of about 120 amino acids, which folds into a structure that binds specifically to the IRF element (IRF E) motifs, which is located upstream of the interferon genes. Some viruses have evolved defense mechanisms that regulate and interfere with IRF functions to escape the host immune system. For instance, the remaining parts of the interferon regulatory factor sequence vary depending on the precise function of the protein. is a cancer virus that encodes four different IRF like genes; including vIRF1, which is a transforming oncoprotein that inhibits type 1 interferon activity. In addition, the expression of IRF genes is under epigenetic regulation by promoter DNA methylation.

IRFs primarily regulate type I IFNs in the host after pathogen invasion and are considered the crucial mediators of an antiviral response. Following a viral infection, pathogens are detected by Pattern Recognition Receptors (PRRs), including various types of Toll like Receptors (TLR) and cytosolic PRRs, in the host cell. Phosphorylated IRFs are translocated to the nucleus where they bind to IRF E motifs and activate the transcription of Type I IFNs. In addition to IFNs, IRF1 and IRF5 has been found to induce transcription of pro inflammatory cytokines. Some IFNs like IRF2 and IRF4 regulate the activation of IFNs and pro inflammatory cytokines through inhibition. IRF2 contains a repressor region that downregulates expression of type I IFNs. IRF4 competes with IRF5, and inhibits its sustained activity. Accumulating evidence also indicates that IRFs play a major role in the regulation of cellular responses linked to oncogenesis. In addition to autoimmune diseases and cancers, IRFs are also found to be involved in the pathogenesis of metabolic, cardiovascular, and neurological diseases, such as hepatic steatosis, diabetes, cardiac hypertrophy, atherosclerosis, and stroke.