Induction of pleckstrin by the Epstein-Barr virus nuclear antigen 3 family

The Epstein-Barr virus (EBV) encoded nuclear antigens, EBNA-3, -4, and -6 (EBNA 3 family) are expressed in latently infected human B-cells and are involved in the transformation of lymphocytes by EBV. Human Burkitt's lymphoma (BL) dG75 cells which stably expressed either the complete EBNA 3 gene family or the vector alone were generated and changes in gene activity in these transfectants were assayed using the differential display of mRNA technique. For the first time, the human gene pleckstrin, which is thought to be involved in signalling and differentiation of hemopoietic cells, was found to be upregulated in the presence of the EBNA 3 protein family, but not in cells expressing the individual EBNA-3, -4, or -6 gene. Pleckstrin was increased up to sevenfold in different cell clones and the bulk culture of EBNA 3 gene family expressing cells as demonstrated by Northern blot. RT-PCR, and immunoblot in contrast to EBV-negative BL cells, pleckstrin RNA and protein were highly expressed in EBV growth transformed lymphoblastoid cell lines which are thought to play an important role in EBV persistence in vivo. These data suggest that induction of pleckstrin might be important for the EBV-controlled activation of cells and offers a unique biological system for analyzing pleckstrin function.