Enhanced rotavirus replication and IEC damage in mice lacking functional IFN-λ receptors. (A–E) Suckling wild-type (n = 12), IL28Rα0/0 (n = 14), IFNAR10/0 (n = 14), and IFNAR10/0IL28Rα0/0 (dKO, n = 12) mice were orally infected with murine rotavirus strain EDIM (5 μL of 1:100 diluted stock). Animals were killed 4 d later. (A) Immunostaining for rotavirus antigen (red) in thin sections of paraffin-embedded intestinal tissue. Counterstaining was performed with wheat germ agglutinin (WGA, green) and DAPI (blue). (Scale bars, 50 μm.) (B) Epithelial rotavirus antigen staining intensity was measured to obtain the relative fluorescence intensity (RFI) of villus/crypt epithelium. (C) Viral antigen levels in colon homogenates were determined by ELISA. Combined results of three independent experiments are shown. To facilitate comparison, OD450nm readings were normalized to the mean values obtained from wild-type mice of each experiment. (D) Histological score of virus-induced small intestinal tissue alterations and (E) H&E stainings of rotavirus-infected tissue. [Scale bars, 50 μm (Top and Middle), 10 μm (Bottom).] (F) Virus shedding in feces of adult wild-type, IL28Rα0/0, IFNAR10/0, and IFNAR10/0IL28Rα0/0 (dKO) mice (n = 8 for each group) after oral infection with murine rotavirus strain EDIM. Each line represents the OD450nm values of one individual mouse during the observed time period.