Ringing the interferon alarm: differential regulation of gene expression at the interface between innate and adaptive immunity

The genes for type I IFNs (IFN-α and IFN-β) are rapidly induced in response to viral infection. IFN regulatory factor (IRF) proteins are key to the regulation of IFN gene expression; the early response to virus results in secretion of a subset of IFN genes through the action of IRF3 in conjunction with additional transcription factors, such as NF-κB and AP-1 (c-jun–ATF2). This early IFN acts in an autocrine manner to stimulate the production of IRF7, a transcription factor capable of activating the many additional members of the IFN-α gene family. The dependence of IRF7 on virus-induced phosphorylation for its activity ensures that IFN production is limited to virus-infected cells. Additional members of the IRF family may provide additional levels of control, in both a cell-type and virus-specific manner, particularly in dendritic cells that serve as major producers of IFN and a key interface between innate and adaptive immunity.