FIG 4 .

Infection in Ifnar1^−/− and Tim1^−/− Ifnar1^−/− mice (four mice in each group) initiated by gradient-isolated quasi-enveloped and naked, nonenveloped fifth mouse-passage virus. (A) HAV RNA in fractions of an isopycnic iodixanol gradient loaded with a lysate of infected Mavs^−/− mouse liver (2). Fractions 10 (eHAV) and 18 (HAV) were used to inoculate mice with comparable amounts of virus based on RNA quantitation (∼10⁸ genome equivalents). (B) Fecal HAV shedding in mice infected by i.v. inoculation of HAV or eHAV (fractionated as described for panel A). Fecal shedding was significantly greater in HAV-infected than eHAV-infected animals at 7 and 10 days postinfection, regardless of the presence or absence of TIM1 (P < 0.001 by two-way ANOVA). Ifnar1^−/− and Tim1^−/− Ifnar1^−/− mice differed in fecal shedding only at day 10 in HAV-infected, not eHAV-infected animals (P < 0.05). There were four mice in each group. (C) Intrahepatic HAV RNA at day 14 postinfection. Less viral RNA was present in Tim1^−/− Ifnar1^−/− mice than in Ifnar1^−/− mice infected with either inoculum (P < 0.05 by two-way ANOVA). (D) Serum ALT on days 7 and 14 postinfection. ALT elevations were consistently lower in Tim1^−/− Ifnar1^−/− mice compared to Ifnar1^−/− mice, but this difference achieved statistical significance only at day 14. Error bars = SEM. *, P < 0.05; ***, P < 0.001.