IFNs are defined by their antiviral activities. They inhibit the replication of many, if not all, viruses mostly by direct inhibition of replication in the infected cells but also by promoting the ability of immune cells to recognize and eliminate the virus-infected cells [25] . The direct effects are mediated by ISGs, which number in the hundreds, and different ISGs are thought to have more potent antiviral activities toward different families of viruses [13] . However, in most cases, it is not known which ISG inhibits the replication of a given virus; the rare exception is the Mx-mediated inhibition of influenza viruses, the underlying effect which allowed for the discovery of IFNs [26] . The task of connecting a specific IFN-induced protein to a specific antiviral action is compounded by the fact that often several IFN-induced proteins act in concert to inhibit the same virus at different stages of its life cycle. Moreover, a specific IFN-induced protein may be more relevant for inhibiting a virus in one specific cell-type than another. Recent systematic investigation of the specific antiviral effects of different ISGs has started providing significant insight into this problem [14] . Such findings are complemented by the analyses of the spectra of the antiviral effects of a specific ISG or a family of ISGs [27] . We have undertaken an investigation of the Ifit family of mouse ISGs. The corresponding human proteins are known to have antiviral activities against human papillomavirus (HPV) and hepatitis C virus (HCV), neither of which replicate in mouse cells. The anti-HPV activity of human IFIT1 ( = P56) has been attributed to its ability to bind HPV E1 protein and to inhibit its helicase activity, which is essential for HPV DNA replication [28, 29] . The antiviral effect on HCV, on the other hand, is manifested at the level of inhibiting viral protein synthesis as a consequence of the ability of IFIT1 to bind the translation initiation factor eIF3 and inhibit its various actions in translation initiation [30] . It has been reported recently that the IFIT1 protein can form a complex and bind to RNAs with triphosphorylated 59 ends, presumably providing another means to inhibit specific viruses that produce such RNAs [18] .