IFN-α and IFN-β protect against CHIKV-induced clinical disease. Shown are data for swelling of the ipsilateral feet of mice inoculated with 103 PFU of CHIKV. Foot swelling was measured daily for wild-type, IFN-β-KO, or IRF7-KO mice (A) or for wild-type mice treated with anti-mouse IFN-α (TIF-3C5), anti-mouse IFN-β (HDβ-4A7), or isotype control antibody 1 day before and 1 day after infection (B), as described in Materials and Methods. Data are reported as percent increases in foot area (vertical × horizontal [square millimeters]) over baseline. Data are pooled from at least two experiments with 18 to 22 mice per group (A) or 10 mice per group (B) and expressed as means ± standard errors of the means (SEM) (*, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 [by two-way ANOVA with Dunnett’s posttest]).