Hepatitis A infection in Tim1−/− Ifnar1−/− (n = 4), Tim4−/− Ifnar1−/− (n = 2), and Ifnar1−/− (n = 4) mice inoculated intravenously (i.v.) with ∼108 genome equivalents (GE) of fifth mouse-passage HM175 virus (mp5 unfractionated liver homogenate). (A) Fecal shedding of HAV by Tim1−/− Ifnar1−/−and Tim4−/− Ifnar1−/−double-knockout mice was similar to single Ifnar1−/− knockouts, but significantly elevated in Tim1−/− Ifnar1−/− versus Ifnar1−/− mice on day 7 postinfection (P < 0.01). (B) Intrahepatic HAV RNA abundance at day 14 (d14) postinfection. (C) Serum ALT on days 7 and 14 postinfection. Bar = mean. (D) H&E-stained liver sections from mock-infected Tim1−/− Ifnar1−/− mice, mp5 HM175 virus-infected Tim1−/− Ifnar1−/− mice, and Ifnar1−/− mice. Virus-infected Tim1−/− Ifnar1−/− and Ifnar1−/− livers show diffuse small inflammatory cell infiltrates with apoptotic hepatocytes (white arrows) scattered throughout the parenchyma. Only minimal numbers of periportal lymphocytes are evident in mock-infected liver tissue. Bar, 100 µm.