Infection of primary CD4+ and CD8+ T lymphocytes by Epstein-Barr virus enhances human immunodeficiency virus expression.

CD4+ and CD8+ T lymphocytes purified from normal adult donors by flow cytometry could be infected with Epstein-Barr virus (EBV) as measured by the accumulation of components of the EBV replicative cycle, viral DNA and viral transcripts encoding EBER1 and BRLF1. EBV infection resulted in enhanced replication of human immunodeficiency virus type 1 (HIV-1) IIIB in CD4+ lymphocytes as measured by accumulation of reverse transcriptase and formation of syncytia. Furthermore, a small percentage of CD8+ T cells became permissive after infection with EBV. Inactivation of transforming functions by irradiation with UV light greatly reduced the ability of EBV to enhance HIV-1 replication in T4+ T cell, suggesting that live virus is needed for enhancement. These results demonstrate a direct synergy between EBV and HIV-1 during coinfection of T cells in vitro and may explain the beneficial effect of acyclovir in combination with antiretroviral chemotherapy as well as the increased incidence of T-cell lymphomas associated with EBV in patients with AIDS.