<p>Viral infections induce the expression of type I interferons (IFN-alpha andIFN-beta) genes. The induction is due to the transcriptional activation of theIFN genes. Interferon regulatory factor I (IRF-1) is one of the transcriptionfactors responsible for that activation. IRF-1 binds to an upstream regulatorycis element, known as the interferon consensus sequence (ICS), which is foundin the promoters of type I IFN and IFN-inducible MHC class I genes. Interferonregulatory factor 2 (IRF-2) is a protein that also interacts with the ICS, butthat does not function as an activator; rather, it suppresses the function ofIRF-1 under certain circumstances [<cite idref="PUB00003185"/>].</p><p>These proteins share a highly conserved N-terminal domain of about 100 aminoacid residues which is involved in DNA-binding and which contain fiveconserved tryptophans. This domain is known as a 'tryptophan pentad repeat' ora 'tryptophan cluster' and is also present in:</p><ul> <li>Interferon consensus sequence binding protein (ICSBP) [<cite idref="PUB00004709"/>], a transcription factor expressed predominantly in lymphoid tissues and induced by IFN-gamma that also binds to the ICS.</li><li>Transcriptional regulator ISGF3 gamma subunit [<cite idref="PUB00003680"/>]. ISGF3 is responsible for the initial stimulation of interferon-alpha-responsive genes. It recognises and binds to the interferon-stimulated response element (ISRE) within the regulatory sequences of target genes.</li><li>Interferon regulatory factor 3 (IRF-3).</li><li>Interferon regulatory factor 4 (IRF-4) which binds to the interferon- stimulated response element (ISRE) of the MHC class I promoter.</li><li>Interferon regulatory factor 5 (IRF-5).</li><li>Interferon regulatory factor 6 (IRF-6).</li><li>Interferon regulatory factor 7 (IRF-7).</li><li>Gamma Herpesviruses vIRF-1, -2 and -3, proteins with homology to the cellular transcription factors of the IRF family [<cite idref="PUB00055524"/>]. Neither vIRF-1 nor vIRF-2 bind to DNA with the same specificity as cellular IRFs, indicating that if vIRFs are DNA-binding proteins, their binding has a pattern distinct from that of the cellular IRFs. Whether vIRF-3 can bind DNA with the same specificity as cellular IRFs is not known.</li> </ul><p>The IRF tryptophan pentad repeat DNA-binding domain has an alpha/betaarchitecture comprising a cluster of three alpha-helices (alpha1-alpha3)flanked on one side by a mixed four-stranded beta-sheet (beta1-beta4). It forms a helix-turn-helix motif that binds to ISRE consensussequences found in target promoters. Three of the tryptophan residues contactDNA by recognising a GAAA sequence [<cite idref="PUB00004269"/>].</p><p>This entry represents the IRF tryptophan pentad repeat DNA-bindingdomain.</p>