Figure 3.

SOD1 Deficiency Leads to Oxidative Stress-Induced Liver Damage upon Viral Infection

(A) Liver sections were stained for 8-oxoguanine (8-oxoG) from uninfected or LCMV infected WT and Sod1^−/− mice. Arrows indicate 8-oxoG positive cells. Numbers of positive nuclei are shown as mean ± SEM (n = 3 mice per group, scale bar represents 200 μm). Representative images are shown.

(B) WT and Sod1^−/− mice were infected with LCMV. Atf3 mRNA levels were determined in liver tissue before and after infection by real-time PCR (n = 3 mice per group). One out of ≥ two similar experiments is shown.

(C) Bone marrow-chimeric mice were generated by reciprocal transfer of Sod1^−/− and WT genotypes. Serum ALT levels of mice infected with LCMV are shown (n = 5-8 mice per group pooled from two experiments). p values are derived from the comparison to the control group of WT→WT mice.

(D) Primary hepatocytes from WT mice were left uninfected or infected with LCMV (MOI 5) +/− treatment with 10 μM CuDIPS before staining with CellROX. Scale bar represents 20 μm. Representative images are shown. Quantification was performed by CellProfiler and numbers represent mean ± SEM. One out of ≥ two similar experiments is shown.

(E and F) WT and Sod1^−/− mice, which received either 10 mg/kg body weight CuDIPS or solvent, were infected with LCMV and (E) serum levels of ALT (n = 12 mice per group, pooled from three independent experiments) and (F) Atf3 mRNA in liver tissue were measured 44 hr after infection (n = 8 mice per time point, pooled from two independent experiments). Statistical significance was calculated by Two-way (A–C, E) or one-way (D and F) ANOVA with Bonferroni correction. Symbols represent the mean ± SEM.