Interestingly, however, viral gene expression did not inhibit the production of IL-6 in either Ad3-or Ad R700-infected mice ( Fig. 1C and Fig. S2D ). Further experiments revealed that, in contrast to the UV-inactivated Ad, heat-inactivated Ad did not elicit IFN-ab in mice (data not shown). Since heat inactivation prevents the entry of Ad into cells ( [44] and Fig. S2E ), we conclude that signal transduction leading to IFN-ab production is activated during Ad entry.