In the above context, we have been investigating the biochemical and biological functions of the members of the Ifit family of ISGs, which are very strongly induced by IFN. There are three members of this family of genes in mice: Ifit1/ISG56, Ifit2/ ISG54 and Ifit3/ISG49; all of the encoded proteins contain multiple tetratricopeptide repeats (TPR), which mediate proteinprotein and protein-RNA interactions [15] . In vitro, P56 and P54, the products of Ifit1 and Ifit2, respectively, bind to the translation initiation factor eIF3 and inhibit protein synthesis [16] . The third member, P49, the product of Ifit3, does not share this property [17] . Recently, it has been reported that Ifit proteins form a multiprotein complex that can bind to the triphosphorylated 59 end of RNAs, an RNA-species produced during the replication of some, but not all, viruses [18] . In vivo, these genes are strongly induced in brains of mice infected with West Nile virus (WNV) or Lymphocytic choriomeningitis virus (LCMV); surprisingly, different Ifit genes are differentially induced in different regions of the brain, suggesting non-redundant functions [19] . To further explore the antiviral properties of the Ifit proteins, we generated Ifit1 knockout (Ifit1 2/2 ) mice and challenged them with different viruses. We observed that Ifit1 2/2 mice were particularly susceptible to a WNV mutant that is defective in its mRNA cap 29-O methylation; the mutant virus killed Ifit1 2/2 mice but not the wild-type (wt) mice [20] .