As mentioned above, the production of IFN-ab in Ad-infected mice is strongly dependent on IFN-ab feedback signaling. Inhibition of positive IFN-ab feedback is a likely explanation for the negative regulation of the IFN-ab response, observed, in mice infected with intact Ads (expressing early genes) in this study. Likely candidates for negative regulators of the IFN-ab production are the E1A proteins. Previously, they were shown to inhibit Stat1 signal transduction [86] , which plays a role in positive feedback signaling by means of the IFN-ab receptor.