The Ifit genes are clustered at a single locus in both human and mouse. In the latter species, two alleles of Ifit3 genes are flanked on two sides by one allele of Ifit2 and one allele of Ifit1 [15] . To identify their physiological functions, we have separately deleted the entire coding regions of Ifit1 or Ifit2 genes. The Ifit1 2/2 mice exhibited an interesting phenotype in allowing the replication of and resultant pathogenesis by a WNV mutant, which failed to replicate in wt mice [20] . Because this mutant is defective in 29-O methylation of the cap structure of viral mRNAs, its rescue in the Ifit1 2/2 mouse indicates that this antiviral protein recognizes the 59 ends of mRNAs, a conclusion that is consistent with the observation that, in vitro, it can bind to RNAs having specific structures at the 59 ends [18] . It remains to be seen whether the proposed property of Ifit proteins to recognize 59 ends of RNA is connected in any way to their ability to inhibit the functions of eIF3 [16] , which participates in several steps of translation initiation taking place at or near the 59 ends of mRNAs.