Depletion of CD8+ T cells during RSV infection prevents weight loss and associated gut microbiota changes, but this is not due to decreased IFN-γ production. CD8+ T cells were depleted during RSV infection by using mouse anti-CD8 monoclonal antibody. Mice were i.p. injected with 500 μg/ml antibody or isotype control before (day −1) and after (D2 and D5) RSV infection. Fecal samples were taken at D0 and D7. Weight loss (A) and food consumption (B) were measured after infection. (C) RSV L gene lung viral load was measured after infection at day 7. (D) Gut microbiota diversity measured at D0 and D7. (E) Relative abundances of Bacteroidetes and Firmicutes after infection (F). Family-level analysis of response after infection. IFN-γ was blocked by injecting mice i.p. with 500 μg/ml anti-mouse IFN-γ antibody or isotype control before (−4 h) and after (D2, D4, and D6) RSV infection. Effect of IFN-γ depletion on weight loss (G) and food consumption (H) during RSV infection. (I) Fold change in lung cytokine levels following CD8 depletion at day 7 compared to that in isotype control group. Significance for weight loss and phyla/family abundance tested using two-way RM ANOVA with Dunnet’s and Sidak’s multiple-comparison tests, respectively. Beta diversity was visualized using principal-coordinate analysis (PCoA) on a Brays-Curtis dissimilarity matrix, as there were insufficient data to perform NMDS. n = 4 to 5 mice per group. Results are from a single experiment.