Interferon regulatory factor-3 (IRF-3) is a transcription factor primarily responsible for inducing interferon (IFN) genes following viral infection. This induction is a central part of the innate immune response. A novel role for IRF-3 following viral infection has recently been discovered; IRF-3 mediates apoptosis following Sendai virus infection in an IFN-independent manner. The precise mechanism by which IRF-3 participates in IFN-independent apoptosis is unknown. The goal of this proposal is to determine the role of IRF-3 in the induction of apoptosis following viral infection. One candidate IRF-3 target gene is TRAIL (TNF-related apoptosis inducing ligand), a molecule that binds to death receptors and leads to apoptosis. I will characterize the mechanisms of IRF-3 TRAIL promoter regulation, as I have the evidence that IRF-3 upregulates TRAIL mRNA following viral infection. In addition, using a proteomic approach, I will identify proteins that interact with IRF-3 both prior to and following Sendai Virus infection. I will also elucidate the specific components of the caspase pathway activated during IRF-3 mediated virally induced apoptosis. These studies will increase our understanding of mechanisms of the innate immune response and will define new targets and pathways governed by IRF-3. ? ?
