[Molecular mechanisms of Epstein-Barr virus-induced lymphoid neoplasms]

Epstein-Barr virus (EBV) infects human beings and latently persists in B-cells throughout life. EBV infection renders B cells immortal. In immunocompetent individuals, the expansion of EBV-infected B-cells is suppressed by cytotoxic T lymphocytes (CTL). However, once immunosuppression-induced CTL dysfunction or accelerated proliferation of infected cells due to gene mutation accumulation occurs, the infected cells proliferate leading to B-cell neoplasms. The products of the viral genome, i.e. LMP1, EBNA2, EBNA3A, and EBNA3C, are indispensable for transformation of infected B-cells. These viral proteins suppress apoptosis of the infected cells and contribute to the expansion of genetic mutation-bearing clones. It was recently reported that EBV also infects T or NK cells, suppresses their apoptosis, and promotes their survival by inducing CD40 and CD137 expressions. These results indicate that EBV may contribute to the development EBV-positive T- or NK-cell neoplasms. EBV-positive lymphoid neoplasms are generally resistant to chemotherapy and patient outcomes have thus been poor. Clarification of the molecular mechanisms underlying disease development is anticipated to lead to the establishment of novel treatment strategies.