A Syndrome of Peripheral Blood T-Cell Infection With Epstein-Barr Virus (EBV) Followed by EBV–Positive T-Cell Lymphoma

Abstract The role of Epstein-Barr virus (EBV) in the pathogenesis of severe, chronic active EBV infection and its complications is unclear. We investigated two Japanese patients diagnosed with severe, chronic active EBV infection who subsequently developed EBV–positive T-cell lymphoma. The patients displayed abnormally high antibody titers to EBV antigens, and had evidence of peripheral blood CD4+T-cell infection with EBV, 19 months and 3 months, respectively, before the diagnosis of EBV–positive T-cell lymphoma. The lymphomas were infected with monoclonal EBV and expressed the EBV latency genes EBNA-1, LMP-1, and LMP-2. Genetic studies showed that the virus detected in the T-cell lymphoma was indistinguishable, with respect to type and previously defined LMP-1 and EBNA-1 gene variations, from virus detected in the peripheral blood T cells 19 months earlier. These studies support an important pathogenetic role of T-cell infection with EBV in chronic active EBV infection and in the EBV–positive T-cell lymphoma that followed.