Epstein-Barr virus: 40 years on

Key Points Epstein–Barr virus (EBV) infection is implicated in the aetiology of several different lymphoid and epithelial malignancies. EBV-encoded latent genes induce B-cell transformation in vitro by altering cellular gene transcription and constitutively activating key cell-signalling pathways. EBV exploits the physiology of normal B-cell differentiation to persist within the memory-B-cell pool of the immunocompetent host. Immunosuppressed transplant patients are at risk of developing fatal EBV-transformed B-cell proliferations, presenting as 'post-transplant lymphomas'. Other EBV-associated tumours show more restricted forms of latent gene expression, reflecting a more complex pathogenesis that involves additional cofactors. Pharmacological and immunotherapeutic approaches are being developed to treat or prevent EBV-associated tumours. Epstein–Barr virus (EBV) was discovered 40 years ago from examining electron micrographs of cells cultured from Burkitt's lymphoma, a childhood tumour that is common in sub-Saharan Africa, where its unusual geographical distribution — which matches that of holoendemic malaria —indicated a viral aetiology. However, far from showing a restricted distribution, EBV — a γ-herpesvirus — was found to be widespread in all human populations and to persist in the vast majority of individuals as a lifelong, asymptomatic infection of the B-lymphocyte pool. Despite such ubiquity, the link between EBV and 'endemic' Burkitt's lymphoma proved consistent and became the first of an unexpectedly wide range of associations discovered between this virus and tumours.