All mice used were of C57BL/6 background and of both sexes; Ifit2 2/2 mice were custom-generated by Taconic Farms, Inc. by flanking exons 2 and 3 of Ifit2, encompassing the complete protein-encoding region, with frt sites in C57BL/6 embryonic stem (ES) cells, and deleting the flanked region by transfection of Flp recombinase. ES cell clones were injected into BL/6 blastocysts, and heterozygous offspring mice were crossed to homozygosity. Ifit1 2/2 mice were generated from C57BL/6 ES cells lacking the whole coding region of Ifit1 (20); ES cells were obtained from the NIH Knockout mouse project (KOMP, allele Ifit1 tm1(KOMP)Vlcg ). The same ES cell line was independently used to generate mice in another study [18] . IFNAR 2/2 mice (lacking Ifnar1) were a gift of Murali-Krishna Kaja (Emory University, Atlanta, GA). Congenic wild-type mice were obtained from Taconic Farms.