Fig. 1. Perforin-deficient mice have chronic brain pathology after TMEV infection. Brains from PFP−/− (A,D, G), Gld(B, E, H) and resistant H-2b (C, F,I) controls infected for 21 d (A–C), 45 d (D–F), and 180 d (G–I) were analyzed. The cerebellum (Crb), brainstem (Bst), cerebral cortex (Cor), hippocampus (Hip), striatum (Stm), corpus callosum (Cco), and meninges (Men) were graded independently on a four-point scale for the presence of inflammation, demyelination, and necrosis as described in Materials and Methods. Severe inflammation and tissue destruction were observed in 21 d infected PFP−/− (A), Gld(B), and resistant H-2b(C) mice. By 45 d, inflammation with parenchymal disease was observed in brains from some of the PFP−/− mice (D), and to a lesser extent in in brains from gld (E), and resistant H-2b mice (F). By 180 d, evidence of chronic tissue destruction was readily apparent in PFP−/− (G) mice and to a lesser extent ingld (H) mice, but had completely resolved in resistant H-2b mice (I).