Improved control of MCMV infection and limited virus-induced pathology after CpG pretreatment are due to activities mediated by type I IFNs and improved CD8⁺T-cell responses elicited in the absence of cross-presentation. (A) Viral titers were measured in the organs of BALB/c mice treated with CpG 15 to 18 hours prior to MCMV infection. The indicated organs were harvested at various times PI and viral titers determined by plaque assay. Data are pooled from 4 independent experiments (n = 5-14 mice per time point). Mean ± SEM are plotted. The dashed line represents the limit of detection of the assay. Mice were injected with saline or CpG 18 hours prior to infection with MCMV and (B) gross spleen morphology and (C) spleen histology examined at day 42 PI. For histology, spleens were stained with H&E and images were taken at ×4 magnification. (D) Serum IFN-α levels were measured by ELISA at the indicated times after CpG administration (n = 3-6 mice per group at each time point). (E) Viral titers were measured in the organs of BALB/c (Wt), BALB.IFNAR1^−/−, and BALB.IFNAR2^−/− mice pretreated with CpG 18 hours prior to MCMV infection. Viral titers in spleens and livers at day 4 PI are shown as mean ± SEM (where n = 5-11 mice per group), pooled from 3 independent experiments. The dashed horizontal line represents the limit of detection of the assay. (F) BALB/c mice were injected with saline or CpG 18 hours prior to MCMV infection. Mice were depleted of CD8⁺ T cells at days −2, 0, 2, and 6 with respect to MCMV infection, using an anti-CD8β antibody (53.5.8). Spleens and livers were harvested at the indicated time points and viral titers measured. Data are pooled from 2 independent experiments (where n = 5-10 mice per time point). P values were determined between CpG + MCMV and CpG + MCMV + anti-CD8β (*P < .05, **P < .01, ***P < .001). ELISA, enzyme-linked immunosorbent assay; H&E, hematoxylin and eosin; Wt, wild type.