Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes

Interferon regulatory factor (IRF) genes encode DNA-binding proteins that a re involved in the innate immune response to infection. Two of these protei ns, IRF-3 and IRF-7, serve as direct transducers of virus-mediated signalin g and play critical roles in the induction of type I interferon genes. We h ave now shown that another factor, IRF-5, participates in the induction of interferon A (IFNA) and IFNB genes and can replace the requirement for IRF- 7 in the induction of IFNA genes, We demonstrate that, despite the function al similarity, IRF-5 possesses unique characteristics and does not have a r edundant role. Thus, 1) activation of IRF-5 by phosphorylation is virus-spe cific, and its in vivo association with the IFNA promoter can be detected o nly in cells infected with NDV, not Sendai virus, while both viruses activa te IRF-3 and IRF-7, and 2) NDV infection of IFNA8 overexpressing cells pref erentially induced the IFNA8 subtype, while IFNA1 was primarily induced in IRF-7 expressing cells. These data indicate that multiple signaling pathway s induced by infection may be differentially recognized by members of the I RF family and modulate transcription of individual IFNA genes in a virus an d cell type-specific manner.