Monocarboxylate transporter antagonism reveals metabolic vulnerabilities of viral-driven lymphomas

Significance Epstein–Barr virus (EBV) infects virtually every human by adulthood with limited symptoms. However, in the context of immune suppression, EBV can cause lymphomas. EBV-associated lymphomas have poor prognoses and limited treatment options, highlighting a need to better understand EBV-mediated tumorigenesis. One common feature of viral replication and cancer is dysregulation of metabolism. Indeed, EBV dramatically reprograms host cell metabolism, up-regulating both oxidative phosphorylation and glycolysis. In this report, we identify metabolic vulnerabilities of EBV-infected primary human B cells, EBV-positive lymphomas, and lymphomas caused by the related oncogenic herpesvirus, KSHV. Pharmacological inhibition of lactate export suppressed these lymphomas and rendered them hypersensitive to metformin and phenformin. These findings together with our mechanistic studies outline a therapeutic strategy for viral lymphomas.