Fig 1.
EBV latency oncoprotein–driven B cell metabolism remodeling.
Schematic diagram demonstrating changes in key metabolic pathways during EBV-driven B cell transformation into LCLs. Relative cell size and pathway activation states are depicted. EBV factors associated with each phase of transformation are noted. Metabolic programs and EBV oncogenic factors that regulate them are displayed below. EBNA, Epstein–Barr nuclear antigen; EBV, Epstein–Barr virus; LCL, lymphoblastoid cell line; LMP, latent membrane protein; ncRNA, noncoding RNA; OXPHOS, oxidative phosphorylation.
Fig 2.
EBV-driven 1C pathway drives nucleotide and glutathione synthesis.
EBNA2 and MYC induce the 1C, glycolysis, and de novo serine synthesis pathways in B cells. They also up-regulate plasma membrane abundance of the GLUT1 and ASCT1/2 transporters to increase glucose and serine import, respectively. Serine pools are further expanded by the de novo serine synthesis pathway, which metabolizes the glycolysis product 3-PG into serine and generate NADH and αKG byproducts. EBV also supports mitochondrial 1C metabolism via up-regulation of the SLC25A32 serine and SFXN1 folate transporters. Mitochondrial 1C metabolism converts serine into glycine, NADPH, and a serine-derived carbon unit (red ball), which is shuttled into the cytosol for use in purine and thymidylate biosynthesis. The carbon-loaded 1C folate carriers 5-10-meTHF and 10-CHO-THF are shown. 1C, one-carbon; 3-PG, 3-phosphoglycerate; 3-PHP, 3-phosphohydroxypyruvate; P-ser, 3-phosphoserine; 5-10-meTHF, 5-10-methylenetetrahydrofolate; 10-CHO-THF, 10-formyl THF; EBNA2, Epstein–Barr nuclear antigen 2; EBV, Epstein–Barr virus.