Epstein-Barr virus (EBV) is associated with several human malignancies including a non-Hodgkin's lymphoma of AIDS patients and transplant recipients, Hodgkin's lymphoma, and Burkitt's lymphoma. In the malignant cells, EBV expresses nine proteins including latent infection membrane protein 1 (LMP1). LMP1 is required for EBV to transform primary B-lymphocytes into indefinitely proliferating cell lines and therefore is likely to be important in the pathogenesis of these lymphomas. The central hypothesis of our investigation is that LMP1 is constitutively activated receptor that drives B-cell proliferation by transducing signals that alter expression of specific cell genes. LMP1 transduces signals through tumor necrosis factor (TNF) receptor associated factors (TRAF), TNF receptor associated death domain protein (TRADD), and TNF receptor interacting protein (RIP) that activate NF-κB and mitogen activated protein kinases (MAPK). Our goal is to delineate the role of these signals in driving B-cell proliferation and to identify the specific cell genes whose expression is altered by LMP1 signals to transform B-cell growth. It is expected that the knowledge gained from such analyses will reveal targets for treating or preventing EBV-associated malignancies. Such results will be of additional significance because of what is also learned about the signaling pathways and cell genes that regulate B-cell growth.