Figure 2: Tumor DNA viruses modify metabolism of the transformed cells. (a) Glucose is metabolized to pyruvate; the latter undergoes Crebb’s cycle in mitochondria. (b) “Aerobic” glycolysis takes place, resulting in lactate production. HIF1A-ARNT and MYC-MAX heterodimers induce expression of a set of genes that are involved in glycolysis. (c) E4ORF1 encoded by adenoviruses induces MYC that lead to activation of glycolysis upon infection. (d) HPV-encoded E6 prevents ubiquitination of HIF1A by VHL protein; EBV-encoded EBNA-3 and EBNA-5 bind to PHD2 and PHD2, correspondingly, leading to inhibition of HIF1A hydroxylation; upon infection with KSHV a cluster of miRNAs is activated, resulting in inactivation of PHDs. This leads to stabilization of the HIF1A protein and, hence, to activation of “aerobic” glycolysis.