Identification of picornavirus proteins that inhibit de novo nucleotide synthesis during infection
Fig 5
CVB3 and EMCV elevate levels of purine and pyrimidine metabolites in hiPSC-CMs.
13C6-glucose isotope tracing study in mock-, CVB3-, CVB3-2Am or EMCV infected hiPSC-CMs (MOI 5, calculated from the HeLa R19 titer, three replicates). Cells were infected, lysed at 2.5, 5, 7.5, 10 hpi and measured by LC-MS to identify metabolites and quantify the different isotopologues. A) Heatmaps showing log2 fold changes of the purine and pyrimidine metabolites between CVB3 infected- and mock-infected cells. Log2 fold changes are calculated based on the mean of three replicates. B) Isotopologue distribution of UDP and ADP. For statistical analysis, linear mixed effect models with an interaction of time and treatment and a random effect of replicate were performed. A rank transformation on the data was performed to ensure a normal distribution of the residuals. p-values between specific groups were calculated by performing a contrast analysis, in which the total labeled fraction was compared between groups. *p < 0.05, **p < 0.01, ***p < 0.001.