MHV-3 was kindly provided by Prof. Q. Ning (Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Wuhan, China). The virus was plaque-purified and then expanded in murine L2 cells. Virus-containing supernatants were collected and stored at -80uC until use. Mice were intraperitoneally (i.p.) injected with 10 PFU/mouse in a total volume of 200 ml. In some experiments, PD-1-deficient mice were infected with MHV-3 (10 PFU) and simultaneously treated with a infection was analyzed by immunohistochemistry. Blue color indicates nuclear DAPI staining. Scale bar = 20 mm. Magnification 6200. NS: not significant different. *p,0.05, ** p,0.01. doi:10.1371/journal.ppat.1001347.g004 combination injection of anti-IFN-c (200 mg/mouse per day, clone: R4-6A2, eBioscience, San Diego, CA, USA) and anti-TNF-a (200 mg/mouse per day, clone: MP6-XT22, eBioscience) mAbs, tissues were isolated for hematoxylin and eosin (H&E) staining to detect damage, and for fgl2 mRNA transcription measured by qPCR (see below). Serum ALT and AST levels were measured by an AU5400 automatic biochemistryanalyzer (OLYMPUS, Japan). In order to monitor the mortality, anti-IFN-c and anti-TNF-a blocking mAbs or rat IgG1 control mAbs were injected everyday for a total of 6 days.