The IFN response to MHV-3 is blunted in USP18−/− mice. Animals infected with MHV-3 were sacrificed on days 0 through 4, with an additional measurement at day 7 for USP18−/− mice (USP18+/+ mice succumbed to disease by day 4 p.i.). (A) mRNA expression of both type I and type II IFN is inhibited in USP18−/− mice. mRNA was harvested from livers of USP18+/+ or USP18−/− mice infected with 50 PFU of MHV-3 and sacrificed at day 3 p.i. (B to D) Serum levels of IFNs were measured by ELISA, as indicated. IFN-α, IFN-β, and IFN-γ levels in the plasma were absent in the USP18−/− mice, whereas USP18+/+ mice were able to induce type I and type II IFN responses. Data are represented as means ± SD (A, n 2; B, n ≥ 2; C, n ≥ 3; D, n ≥ 3). ***, P < 0.001; **, P < 0.01; *, P < 0.05.