Epstein-Barr Virus Involvement in T-Cell Malignancy: Significance in Adult T-Cell Leukemia

Abstract

Epstein-Barr virus (EBV) was first reported as the causative virus of Burkitt's lymphoma in 1964. Since then, EBV has also been associated with infectious mononucleosis, AIDS and transplant-related B cell lymphomas, and nasopharyngeal cancer. The virus has further been linked with T cell lymphomas, Hodgkin disease, and NK leukemia or LGL leukemia, establishing a concept of a wide spectrum of EBV associated malignant disorders. EBV DNA encodes several proteins such as EBNA1–6, LMP 1, 2 and others. Recent studies have demonstrated that EBNA2, EBNAS, EBNA3A, EBNA 3C are essential for transformation, and that any gene product is not sufficient to transform cells by itself. Further there are different mechanisms of virus-associated transformation or carcinogenesis among EBV-associated malignant disorders. On the other hand, human T lymphotropic virus type I (HTLV-I) is known as a causative virus of adult T cell leukemia (ATL). However, precise molecular mechanisms of Ieukemogenesis in ATL still remains unclear. Some additional factors to HTLV-I infection are supposed to be involved in complete leukemogenesis. We demonstrated that HTLV-I infected T cells and primary ATL cells express EBV receptor/CD21 on the cell surface. Therefore, it is possible that EBV infection is one of the factors. We further investigated this possibility in 6 HTLV-I infected T cell lines and primary ATL cells from 18 patients with ATL. However, no EBV genome was detected in both T cell lines and primary ATL cells. EBV involved T-cell lymphoma has unique clinical manifestations as compared to non-EBV involved T-cell lymphoma. Therefore, it is still possible that a small group of ATL patients with unique clinical manifestations is associated with EBV.