To investigate the potential role of PD-1 signaling in regulating FH tissue pathology, organs from MHV-3 infected PD-1-deficient (PD-1 KO) and WT mice were assessed for morphological differences. Small and discrete foci of necrosis with sparse polymorphonuclear leukocyte infiltration were observed in liver tissues from PD-1-deficient mice after 24 h of infection. In contrast, WT mice exhibited normal liver architecture at this time point. Slight liver damage became apparent in WT mice after 48 h of infection, meanwhile, the damaged areas of PD-1-deficient mice had enlarged and confluent necrosis had become evident. By 72 h of infection, the damaged region in PD-1-deficient mice had extended throughout the entire liver, while WT mice suffered much less damage and up to 60% of their liver tissue remained normal at this time point ( Fig. 2A) . Likewise, higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed in serum from PD-1-deficient mice after 72 h of infection (Fig. 2B ). More interestingly, PD-1-deficient thymus, spleen and lymph node tissues infected with MHV-3 for 72 h exhibited severely disrupted architecture, loss of cellularity, and the presence of substantial amounts of karyorrhectic/apoptotic cell bodies. The histology of these organs from infected WT mice at 72 h was relatively normal (Fig. 2C ). In conjunction with the apparent tissue necrosis, higher levels of cell apoptosis were also evidenced in the organs from PD-1-deficient mice by TUNEL staining (Fig. 2D ). The architecture of other organs, including the heart, kidney and lung was relatively normal and only rare apoptosis events were observed in these tissues after infection (Fig.  S2 ). In all, these results demonstrated that PD-1 deficiency led to enhanced pathological damage by MHV-3 in the liver, spleen, lymph node and thymus, where higher levels of PD-1-positive cells were found after infection.