The transcription factors IRF-3 and IRF-7 have distinct and important roles in IFN-ab production induced by viruses or other pathogens and their involvement can be characteristic for the induction mechanisms involved [13] . Specifically, IRF-3 has been shown to be critically involved in cytoplasmic DNA sensing and in the Ad-induced IFN-ab production in BMMs in vitro [63] . We show here that IRF-3 is critical for the induction of IFN-ab by isolated adenoviral DNA, but not by infection with whole virions in BMDCs (Fig. 7A ). In order to analyze the individual contribution of IRF-3 and IRF-7 to the Ad-induced IFN-ab response in vivo, we infected mice deficient for these transcription factors with Ad3. We also compared these responses to those triggered by poly I:C, a known activator of the cytosolic IFN-ab producing pathway in vivo. As shown in Fig. 7B , the lack of IRF-3 did not significantly influence the plasma levels of IFNab 4 or 8 h after infection in response to Ad. In contrast, Ad-infected IRF-7deficient mice did not exhibit detectable amounts of IFN-ab in the plasma. Very similar data were obtained with Ad5GFP (Fig. S9) . Thus, IRF-7, but not IRF-3, is essential for the induction of the IFN-ab response during Ad infection. Compared to wt mice, poly I:C injected IRF-7 deficient mice produced significantly less, but still well detectable amounts of IFN-ab.