The role of Epstein-Barr virus in neoplastic transformation

In this review, we focus on new data from basic, translational and clinical research relating to the Epstein-Barr virus (EBV). Beside its well-known t ropism for B lymphocytes and epithelial cells, EBV also infects T lymphocyt es, monocytes and granulocytes. After primary infection, EBV persists throu ghout the life span in resting memory B cells, from where it is reactivated upon breakdown of cellular immunity. In the process of neoplastic transfor mation, the EBV-encoded latent membrane protein 1 (LMP1) oncogene represent s the major driving force. LMP1 acts like a constitutively activated recept or of the tumor necrosis factor receptor family and allows the amplificatio n or bypassing of physiological regulatory signals through direct and indir ect interactions with proteins of the tumor necrosis factor receptor-associ ated factor (TRAF) family. TRAF2-mediated NF-kappaB activation, AP-1 induct ion and JAK3/STAT activation may result in sustained proliferation leading to lymphoma. The ability of LMP1 to suppress germinal center formation and its capacity to mediate its own transcriptional activation shed new light o n the pathogenesis of EBV-associated latency type lymphoproliferations like Hodgkin's disease and angioimmunoblastic lymphadenopathy. The carboxy term inus of LMP1 is also a reliable marker for individual EBV strain identifica tion and thus offers new possibilities in tracing the molecular events lead ing to posttransplant lymphoproliferative disorders (PTLDs). Cytotoxic T ly mphocytes directed against well-characterized epitopes of EBV latency genes represent an already successful and promising therapeutic approach to EBV- associated lymphomas, in particular PTLDs. Copyright (C) 2001 S. Karger AG, Basel.