EBV lytic infection enhances transformation of B-lymphocytes infected with EBV in the presence of T-lymphocytes.

Epstein-Barr virus (EBV) establishes lifelong latency in B-lymphocytes following infection. Although in immune-competent individuals EBV remains in a quiescent state, in immunodeficient individuals, such as those with AIDS or transplant recipients, B-lymphocytes infected with EBV proliferate to give rise to lymphoproliferative diseases. Similarly, in vitro, EBV transforms human B-lymphocytes into indefinitely growing lymphoblastoid cell lines (LCLs) in the absence of cytotoxic T-lymphocytes. Although LCLs harbor the entire EBV genome as an episome, in most cells the virus remains in a latent state expressing a fraction of EBV genes, and lytic infection occurs spontaneously but only in a small percentage of cells. Here, we report that lytic infection contributes to EBV-induced lymphoproliferation by a paracrine mechanism. An EBV immediate-early protein, BZLF1, induces IL-13, thus facilitating the proliferation of EBV-transformed B-lymphocytes in the presence of T-lymphocytes. These data suggest that lytic gene products could contribute to virus-induced oncogenesis by a paracrine mechanism.