Fig. 4: HDV infection inhibits the TCA cycle activity and respiration.

A Isotope tracing. Scheme: distribution of 13C carbons from tracers (13C6 glucose, red; 13C5 glutamine, violet) in TCA cycle metabolites. Graphs: relative isotopologue fractions measured in mock and HDV-infected HepaRGNTCP cells treated with glucose-13C6 or glutamine-13C5 for the last 10 h or 3 h of infection, respectively. Isotopologues used for the measurement from glucose/glutamine: citrate M + 2/M + 4; αKG M + 2/M + 4; succinate M + 2/M + 4; malate M + 2/M + 4. Mean +/− SD, normalized to mock cells, n = 4. B Oxygen consumption rates (OCR) were measured in mock and HDV-infected HepaRGNTCP cells. A representative experiment (left panel, mean +/− SEM) and relative OCR (right panel, mean +/− SD, normalized to basal OCR in mock cells, n = 5) are shown. C OCR was measured in mock and HDV-infected HepaRGNTCP cells treated or not with 1 μM rux for the last 4 days of infection, normalized to basal OCR in mock cells, n = 2. Statistical analysis: for A, (B, right panel) and C data are shown as mean +/− SD. For (B, left panel) data are shown as mean +/−SEM. For (A) Mann-Whitney or t-test were used. For (B, right panel and C) one-way ANOVA with Dunn’s multiple comparison test was used. ****p < 0.0001; ***p < 0.001; **p < 0.01; *p < 0.05.