To further demonstrate that IFN-c and TNF-a were responsible for the observed FGL2 up-regulation in MHV-3 infected PD-1deficient mice, PD-1-deficient mice were infected with MHV-3 and simultaneously treated with a combination injection of anti-IFN-c and anti-TNF-a blocking mAbs. The expression of fgl2 was measured by qPCR and protein detected by immunohistochemistry. The transcription of fgl2 mRNA (Fig. 7A ) and its protein levels (Fig. 7B) were completely inhibited by 48 h after injection of anti-IFN-c and anti-TNF-a mAbs, as compared to the control rat IgG1 isotype antibodies-treated group. Moreover, the tissue necrosis (Fig. 7C ) and liver damage (as indicated by ALT and AST levels) (Fig. 7D ) in PD-1-deficient mice were also significantly reduced, thus the MHV-3-mediated mortality rates were decreased as well (Fig. 7E ).