The type of virus, the IFN-ab-producing target cell, and the activation mechanism determines whether positive feedback signaling is involved in the induction of the IFN-ab response or not [13, 20] . Here, we studied the possible involvement of IFN feedback signaling in the IFN-ab and IL-6 response to Ad3 by using wt and IFN-abR-deficient mice. The absence of the IFN-ab receptor resulted in dramatically decreased levels of IFN-a and IFN-b protein in the plasma as well as of IFN-a and IFN-b mRNAs in the spleen (Fig. 5A , B) 4 and 8 h after Ad infection. The difference between the protein or mRNA levels of IFN-a and IFN-b in wt versus mutant animals was approximately 100 and 20fold, respectively. Furthermore, in contrast to wt mice, the characteristic rise in IFN-ab levels between 4 and 8 h after infection was absent in IFN-abR 2/2 mice. Thus, in Ad-infected mice, production of both IFN-a and IFN-b is strictly dependent on positive IFN-ab feedback. The determination of IL-6 protein and mRNA levels in the same plasma and splenic tissue samples revealed that the induction of IL-6 is also positively regulated by IFN-ab signaling (Fig. 5C ), which is in agreement with a previous study [10] .