Apoptosis is promoted by the dsRNA-activated factor (DRAF1) during viral infection independent of the action of interferon or p53

An apoptotic cellular defense mechanism is triggered in response to viral d sRNA generated during the course of infection by many DNA and RNA viruses. We demonstrate that apoptosis induced by dsRNA or a paramyxovirus is indepe ndent of the action of interferon as it can proceed in a variety of cell li nes and primary cells deficient in an interferon response. Initiation of ap optosis appears to be triggered by activation of a cellular transcription f actor, the dsRNA-activated factor (DRAF1), DRAF1 is composed of interferon regulatory factor 3 (IRF-3) and the transcriptional coactivators CREB bindi ng protein (CBP) or p300. We find that activation of IRF-3 in the absence o f viral infection stimulates apoptosis, In addition, a negative interfering mutant blocks both target gene induction and apoptosis, demonstrating a re quirement for gene expression by IRF-3/DRAF1 to promote apoptosis. IRF-3/DR AF1 target gene expression is also induced in response to a distinct apopto tic stimulus, the DNA damaging agent: etoposide, The activity of the p53 tu mor suppressor does not appear to be required for IRF-3/DRAF1-mediated apop tosis.