On the whole, our findings do not support the participation of any known nucleic acid-mediated mechanisms in the elicitation of IFN-ab responses to human Ads. In this context it is interesting that, as shown here, mouse embryonal fibroblasts do not produce IFN-ab upon Ad infection, although they posses efficient cytosolic induction pathways for dsRNA or dsDNA [13, 36, 37] , the latter shown also in this study. Rather, our data support the possibility that the IFN-ab response to Ads occurs via a novel, not yet characterized cytosolic DNA or protein recognition pathway. Further studies are required to identify the viral components and the host receptors involved. We also emphasize that the known extra-and intra-cytosolic induction pathways may contribute to the IFN-ab response in a host in which Ads replicate and free viral dsRNA and dsDNA are generated.