Figure 5.

Mitochondrial 1C-derived NADPH Is an EBV Dependency Factor

(A) Whole-cell NADPH/NADP⁺ ratios in primary B cells at the indicated time points post-EBV infection. Shown are mean ± SEM values from n = 4 replicates. ^∗p < 0.05; ^∗∗p < 0.01 (one-sample t test).

(B) Whole-cell NADH/NAD⁺ ratios in primary B cells at the indicated time points post-EBV infection. Data show the mean ± SEM values from n = 4 replicates. n.s., not significant (one-sample t test).

(C) LC-MS analysis of NADP⁺ and NADPH cofactors in primary B cells at 4 DPI fed [2,3,3-²H]-serine for 4 h in the presence of either DMSO or SHIN1 (10 μM). Data show the mean with SEM, n = 4. Natural isotope correction was not performed.

(D) Left: Growth curves of GM12878 LCLs with stable GFP, TPNOX, or MitoTPNOX expression. Data show the mean ± SEM, n = 3. n.s., not significant; ^∗∗∗p < 0.005 (unpaired two-tailed t test). Right: a representative immunoblot of whole-cell extracts for FLAG-tagged TPNOX or MitoTPNOX and tubulin load-control, n = 3.

(E) Quantitation of overall NADH/NAD⁺ (black) and NADPH/NADP⁺ (red) ratios in Cas9+ GM12878 LCLs expressing the indicated control or MTHFD2-targeting sgRNA as well as the indicated GFP or MTHFD2^R rescue cDNA. Data show the mean + SEM, n = 3. n.s., not significant; ^∗∗∗p < 0.005 (one-sample t test).

See also Figure S7.