FIG 1.

Localized impact of IAV infection in lung tissue and serum. n = 16 infected mice and n = 10 uninfected mice. (A) 3D model of lung tissue showing sampling positions. (B) Median viral burden distribution of IAV (expressed as relative luminescence units, RLU). Lower infection levels were observed in the trachea (Dunn’s test, FDR-corrected, P < 0.05 for comparisons between trachea and all positions except left lung middle [position 3]). (C) Magnitude of metabolic perturbation compared to uninfected (PERMANOVA R²). (D) Principal coordinate analysis (PCoA) plot showing differences in overall metabolome by sample type (PERMANOVA P value, <0.001). Green enlarged circles represent trachea samples. Faded circles represent uninfected samples. (E) Impact of infection on overall lung tissue metabolome (PERMANOVA P value, <0.001). (F) No significant impact of infection on the overall serum metabolome by PCoA. (G to I) Unique and common metabolites perturbed by infection. (G) Most metabolites perturbed by infection in serum samples are found in both infected and uninfected samples, albeit at different levels. Four of eight metabolites were increased by infection and four of eight were decreased by infection, while only one of the statistically significant metabolites was uniquely observed only in uninfected serum samples. (H) Overlap of metabolites perturbed by infection in serum (orange) or lung tissue all positions combined (green). (I) Most metabolites perturbed by infection in lung samples are found in both infected and uninfected samples, albeit at different levels (181/382 metabolites increased by infection and 181/362 decreased by infection, with 11 of the statistically significant metabolites uniquely detected in uninfected lung tissue). Panels C to I were generated from the full-feature table, generated, filtered, and processed as described in Materials and Methods, including both annotated and unannotated metabolite features.