To understand the mechanisms of PD-1 deficiency-mediated tissue damage and mortality, we performed a comparative genome-wide microarray analysis (NimbleGen) of genes expressed in liver tissues of PD-1-deficient and WT mice after 72 h of MHV-3 infection. The most notable finding was pronounced upregulation (3.75-fold) in the liver of PD-1-deficient mice of the fgl2 transcripts (Fig. 4A) , the protein product of which has been demonstrated to induce lethality of MHV-3-induced FH [5] . In addition, the enhanced fgl2 expression was confirmed by quantitative (q)PCR, results revealed a 2.84-fold and 5.72-fold higher level was present in liver from WT and PD-1-deficient mice, respectively, after 72 h of MHV-3 infection, as compared to their uninfected controls. Moreover, its level in PD-1-deficient liver was 2.01-fold higher than that in the WT group at this time point (Fig. 4B) . Immunohistochemistry was used to show that FGL2-positive cells were present in necrotic liver tissues in PD-1deficient mice at 24 h after MHV-3 injection. The protein expression was found to be enhanced rapidly upon infection, and the highest level occurred at 72 h post-infection. However, occasional FGL2-positive cells were detected in the livers of WT mice at 24 h post-MHV-3 infection and these cells were also present, and slightly enhanced in number, at both the 48 h and 72 h time point (Fig. 4C ). Western-blot was used to verify the higher FGL2 protein level in the livers of PD-1-deficient mice, as compared to WT littermates after 72 h of infection (Fig. 4D ).