The PD-1 signaling is best known for its ability to inhibit or dampen the immune response. Most of the evidence for this function, however, comes from models of tolerance or chronic infections [11, 12, 13, 14 15] . Although some studies have indicated that this signal might also participate in regulating acute infections [23, 24, 25, 26] , its functions in this disease condition are much less clear. Here, we used a mouse FH model mediated by MHV-3 infection to describe the effects of PD-1 in this disease process. Firstly, PD-1 was found to be significantly up-regulated on T cells, macrophages and NK cells within the thymus, spleen, lymph nodes and liver in response to MHV-3 infection. To determine the exact role of PD-1 in the pathogenesis of FH, PD-1deficient mice were used to establish an infection model. Interestingly, MHV-3-induced liver damage in PD-1-deficient mice occurred rapidly and the lesion area was much larger than in their WT littermates. We then extended our investigation to the thymus, spleen and lymph nodes, where increased PD-1-positive cells were observed post-infection. Surprisingly, severe tissue necrosis and substantial apoptosis was observed in these organs of PD-1-deficient mice at 72 h after MHV-3 infection. In contrast, these organs from WT mice exhibited relatively normal histology, a finding in agreement with previously reported results [27] . Taken together, these results suggested that PD-1 deficiency promoted expansion of the pathological damage from the liver to the lymph organs, including the spleen, lymph node and thymus in this FH model, thereafter, the absence of PD-1 was associated with higher mortality rates in response to MHV-3 infection.