Development of EBV-positive T-cell lymphoma following infection of peripheral blood T cells with EBV

Chronic active Epstein-Barr virus (EBV) infection is manifested clinically by the persistence of infectious mononucleosis-like symptoms or its complic ations for a prolonged period ranging from one to several years. This syndr ome may include severe disease manifestations and can be fatal. The role of EBV in the pathogenesis of chronic active EBV infection has been unclear. We investigated two Japanese patients with severe chronic active EBV infect ion who subsequently developed EBV-positive T-cell lymphoma. We found that the patients had evidence of EBV infection in the peripheral blood CD4(+) T -cells 19 and 3 months, respectively, before the T-cell lymphoma was diagno sed. The lymphomas were infected with monoclonal EBV and expressed the EBV latency genes EBNA-1, LMP-1, and LMP-2A, a virus latency pattern referred t o as latency LI. Genetic studies showed that the virus detected in the T-ce ll lymphoma was indistinguishable from the virus in the peripheral blood CD 4(+) T-cells. These studies support an important pathogenetic role of T-cel l infection with EBV in chronic active EBV infection and in the EBV-positiv e T-cell lymphoma that followed.