Metabolic Reprogramming in Epstein-Barr Virus Associated Diseases

Epstein-Barr virus (EBV) is the first human cancer-causing viral pathogen to be discovered; it has been epidemiologically associated with a wide range of diseases, including cancers, autoimmunity, and hyperinflammatory disorders. Its evolutionary success is underpinned by coordinated expression of viral transcription factors (EBV nuclear antigens), signaling proteins (EBV latent membrane proteins), and noncoding RNAs, which orchestrate cell transformation, immune evasion, and dissemination. Each of those activities entails significant metabolic rewiring, which is achieved by viral subversion of key host metabolic regulators such as the mammalian target of rapamycin (mTOR), MYC, and hypoxia-inducible factor (HIF). In this review, we systemically discuss how EBV-encoded factors regulate metabolism to achieve viral persistence and propagation, as well as potential research questions and directions in EBV-driven metabolism.