<i>IL-18</i>^<i>-/-</i> mice are susceptible to MHV-3-mediated hepatitis.

<p><i>IL-18</i>^<i>-/-</i> mice and their C57BL/6 WT littermates were treated with MHV-3 (100PFU). <b>(A)</b> Peritoneal exudative macrophages (PEMs) and liver tissues were isolated from C57BL/6 WT mice, and the transcription of <i>proIL-18</i> mRNA was measured by qPCR. *<i>p</i> < 0.05. <b>(B)</b> Serum IL-18 levels in virus-infected WT mice at the indicated time points were measured by ELISA. **<i>p</i> < 0.001, n = 5~8 <i>per</i> group, NS: no significant difference. <b>(C)</b> RAW264.7 cells and SVE-10 endothelial cells were treated with IFN-γ (50 ng/ml), TNF-α (100 ng/ml) and IL-18 (20 ng/ml) alone or in combination, and <i>fgl2</i> mRNA transcription was detected by qPCR at 24h. *<i>p</i> < 0.05, NS: no significant difference. <b>(D)</b> The expression of FGL2 in MHV-3 infected livers was compared by western-blotting. Three representative samples <i>per</i> group are shown. <b>(E)</b> Liver fibrinogen deposition was analyzed by immunohistochemistry, architecture was detected by H&E staining, and cell apoptosis by TUNEL staining. Scale bar 20 μm, arrows indicates TUNEL-positive cells, blue color indicates nuclear staining with 4',6-diamidino-2-phenylindole (DAPI), n = 5 <i>per</i> group. <b>(F)</b> Liver expression of Bgp1 was detected by western-blot (up) and the virus titers in livers at 72h post-infection were analyzed by plaque assay, and their levels were compared by statistical analysis (down). *<i>p</i><0.05, n = 5 <i>per</i> group. <b>(G)</b> The survival rate of virus-infected mice was monitored for 20 days. One of three experiments with similar results is shown. NS: no significant difference.