Epstein-Barr Virus Promotes B Cell Lymphomas by Manipulating the Host Epigenetic Machinery

During the past decade, the rapid development of high-throughput next-generation sequencing technologies has significantly reinforced our understanding of the role of epigenetics in health and disease. Altered functions of epigenetic modifiers lead to the disruption of the host epigenome, ultimately inducing carcinogenesis and disease progression. Epstein-Barr virus (EBV) is an endemic herpesvirus that is associated with several malignant tumours, including B-cell related lymphomas. In EBV-infected cells, the epigenomic landscape is extensively reshaped by viral oncoproteins, which directly interact with epigenetic modifiers and modulate their function. This process is fundamental for the EBV life cycle, particularly for the establishment and maintenance of latency in B cells; however, the alteration of the host epigenetic machinery also contributes to the dysregulated expression of several cellular genes, including tumour suppressor genes, which can drive lymphoma development. This review outlines the molecular mechanisms underlying the epigenetic manipulation induced by EBV that lead to transformed B cells, as well as novel therapeutic interventions to target EBV-associated B-cell lymphomas.