Figure 3. Immune response to BRBV in vivo. A) B6 WT (n = 5) mice or animals with a knockout in IFNAR (IFNAR^−/−) (n = 6), IL28R^−/− (n = 6), IFNAR^−/− IL28R^−/− double knockout (n = 6), or STAT1^−/− (n = 7) infected intraperitoneally with BRBV (1000 pfu). Liver, lung, spleen, and kidney were harvested at day 4 and viral titers determined. B) B6 WT animals (n = 4/group) treated with monoclonal antibodies directed against IFNAR-1 (0.5 mg/mouse 24 h before and 24 h after infection) or against IFN-γ (1 mg/mouse 24 h before and 48 h after infection) and infected with BRBV (100 PFU) for 4 d. C, D) B6 WT animals (4 per group) treated as in panel B and weight loss (mean +SEM) and survival monitored. Animals were euthanized if they lost >25% bodyweight or showed severe clinical signs. E) IFNAR^−/− IL28R^−/− mice treated with α-IFNγ antibody (n = 11) or left untreated (n = 7) as described in panels B–D and STAT1^−/− (n = 8) animals infected with BRBV (100 PFU). At day 4, postinfection viral titers were determined. F, G) The mice (E) together with additional B6 WT (n = 9) were monitored for weight loss (mean +SEM) and survival as in panels C and D. In panels A, B, and E, geometric means are displayed and dotted lines indicate detection limits. Statistical analyses were performed on log-transformed values with a 1-way analysis of variance (Tukey multiple comparison test). Statistics are presented in comparison to the respective organs of IFNAR^−/− (A), α-IFNAR (B), or IFNAR^−/− IL28R^−/− (E). BRBV, Bourbon virus; dpi, days postinfection; IFN, interferon; IFNAR, type I interferon receptor; KI, kidney; LI, liver; LU, lung; NS, nonsignificant; SP, spleen; WT, wild-type. ***p<0.001.