(A) Groups of non-BMT (n = 5), BMT (n = 5), or IDO^–/– BMT (n = 5) mice were infected for 7 days with γHV-68. Lungs were collagenase digested and expression of TDO2 was analyzed by qRT-PCR. (B and C) Groups of non-BMT or BMT mice were infected with γHV-68 and treated with the TDO2-specific inhibitor 680C91 (10 μg per mouse every 2 days) for 7–14 days by i.p. injection. At 7 dpi, concentration of kyn was assessed from whole-lung homogenate via ELISA (B shown as mean ± SEM, non-BMT and BMT groups n = 3, BMT + 680C91 n = 5 mice per group). At 21 dpi, lungs were harvested, and lung collagen content was assessed by hydroxyproline assay (C shown as mean ± SEM, non-BMT n = 5, BMT n = 11, BMT + 680C91 n = 9). (D–F) Flow cytometry analysis of lung leukocytes harvested at 7 dpi and analyzed for the indicated lymphocyte population (shown as mean ± SEM, non-BMT n = 4, BMT n = 5, CH223191 [AHR antagonist] n = 5, 680C91 [TDO2-specific inhibitor] n = 5, both given at doses of 10 μg per mouse every other day). (G) Representative micrographs of lung sections taken from BMT mice infected with γHV-68 for 21 days. (H) Collagen fibers of micrographs from trichrome-stained lung sections were quantified in ImageJ (NIH; shown as mean ± SEM, n = 5 random fields per image). (I–K) Fibroblasts were isolated via “crawl-out” method from minced lung. Fourteen days after isolation, cells were infected with γHV-68 (MOI = 1.0) or mock infected for 24 hours, after which expression of the indicated transcript was analyzed by qRT-PCR (shown as mean ± SEM, n = 6 samples per group in I and J, n = 3 samples per group in K). Statistical significance was determined by ANOVA in panels A–F and Student’s t test in panels H–K, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.