Overexpression of wild-type IDH2 is responsible for EBV-LMP1-modulated metabolic changes. A, the patients were divided into two groups based on their serum EBV DNA copy number: 1) low-level group = EBV DNA ≥1 × 103 copies and 2) high-level group = EBV DNA<1 × 103 copies. Serum 2-HG levels were compared between the two groups (left). The correlation between serum 2-HG levels and VCA-IgA levels was analyzed (right). B, serum 2-HG levels were compared among different stages of regional lymph node metastases N stage. The levels of 2-HG (left) and α-KG (right) were measured in C, NPC cells transfected with empty or LMP1 expressing vector, D, in NPC cells transfected with empty or IDH2 expressing vector, in E, NPC cells transfected with scramble or IDH2 shRNAs, and in F, xenograft tissues from mice inoculated with HNE2-LMP1 cells transfected with scramble or IDH2 shRNA-1. Viability was measured by MTS in cells treated with G, DMSO/1 mM octyl-2-HG, and H, cells treated with DMSO/1 mM octyl-α-KG. Data are presented as means ± S.D.; ∗, p < 0.05; ∗∗, p < 0.01; ∗∗∗, p < 0.001.