THE EPSTEIN-BARR-VIRUS TRANSFORMING PROTEIN LMP1 ENGAGES SIGNALING PROTEINS FOR THE TUMOR-NECROSIS-FACTOR RECEPTOR FAMILY

The cytoplasmic C-terminus of Epstein-Barr virus (EBV) latent infectio n membrane protein 1 (LMP1) is essential for B lymphocyte growth trans formation and is now shown to interact with a novel human protein (LMP 1-associated protein 1 [LAP1]). LAP1 is homologous to a murine protein , tumor necrosis factor receptor-associated factor 2 (TRAF2), implicat ed in growth signaling from the p80 TNFR. A second novel protein (EBI6 ), induced by EBV infection, is the human homolog of a second murine T NFR-associated protein (TRAF1). LMP1 expression causes LAP1 and EBI6 t o localize to LMP1 clusters in lymphoblast plasma membranes, and LMP1 coimmunoprecipitates with these proteins. LAP1 binds to the p80 TNFR, CD40, and the lymphotoxin-p receptor, while EBI6 associates with the p an TNFR. The interaction of LMP1 with these TNFR family-associated pro teins is further evidence for their role in signaling and links LMP1-m ediated transformation to signal transduction from the TNFR family.