IRF-3 can inhibit cell growth and plays a critical role in controlling the expression of genes in the innate immune response. In unstimulated cells, IRF-3 is present in the cytoplasm. Viral infection results in phosphorylation of IRF-3 and leads to its translocation to the nucleus where it activates promoters containing IRF-3-binding sites. Phosphorylation of IRF-3 occurs at a cluster of C-terminal Ser and Thr residues (between 385 and 405), leading to its association with the p300/CBP coactivator protein that promotes DNA binding and transcriptional activity. During infection, IRF-3 is likely activated through a pathway that includes activation of Toll-like receptors and a kinase complex that includes IKK? and TBK1. IRF-3 is phosphorylated at Ser396 following viral infection, expression of viral nucleocapsid, and double-stranded RNA treatment. These events likely play a role in activation of IRF-3.