Viral infection activates cellular IRFs, including IRF1, 3, 5, and 7 to initiate IFN transcription. Binding of cellular IRFs by vIRF1 or vIRF3 results in a blockade of IFNα, β, and γ transcription. vIRF1 inhibits type I IFN transcription by binding the CBP/p300 transcriptional coactivator and inhibiting its activity. Viral infection also induces NF-κB transcription that is decreased by vIRF3. vIRF1, 3, and 4 inhibit p53 transcription and impede p53-mediated cell death. Other cell death processes affected by vIRFs include vIRF1 binding to GRIM19, vIRF3 interaction with 14-3-3 and FOXO3a, vIRF1 and 2 blockade of CD95L production, and vIRF1-mediated nuclear localization of Bim. In addition to deregulating immune responses and cell death, vIRFs have other roles such as vIRF3 increasing Myc and HIF-1α transcription and blocking expression of MHC II. vIRF1 blocks TGF-β signaling through binding to Smad3 and Smad4 and vIRF4 binding to the Notch transcription factor, CSL/CBF1 to inhibit activation of Notch target genes.
Front. Immunol., 17 June 2011 | doi: 10.3389/fimmu.2011.00019