Although Isg20−/− mice were not more susceptible to infection with wild-type (WT) pathogenic strains of CHIKV or VEEV, an IFIT1-sensitive mutant of VEEV was more virulent in Isg20−/− mice and replicated to higher levels in some, but not all, Isg20−/− primary cells than in the WT counterparts. This evidence concerns the gene IFIT1 and infection.