Epstein-Barr virus signal transduction and B-lymphocyte growth transformation

Latent EBV growth transformation of resting B-cells into indefinitely proliferating cell lines is a successful viral strategy for survival in its host and the basis of several human malignancies. EBV transforms cell growth through viral proteins that modify cell gene expression at the level of transcription or by appropriating signaling pathways. Analyses of the EBV-transforming protein LMP1 have begun to reveal that this receptor transduces critical signals by appropriating the TNF receptor signal transduction pathway to activate NF-kappaB and MAPK. While this has brought an important aspect into clearer focus, future progress in delineating the underlying mechanism of transformation, which will be essential to devising effective therapies to treat EBV-associated malignancies, will depend on resolving the intricacies of TRAF signal transduction. Since expression of cytokines, receptors, and anti-apoptotic proteins are regulated by TRAF signaling, another critical issue is delineating the genes that are specifically targeted by LMP1 in order to transform B-lymphocyte growth.