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 a nd are involved in the transformation of lymphocytes by EBV. Human Bur kitt's lymphoma (BL) dG75 cells which stably expressed either the comp lete EBNA 3 gene family or the vector alone were generated and changes in gene activity in these transfectants were assayed using the differ ential display of mRNA technique. For the first time, the human gene p leckstrin, which is thought to be involved in signalling and different iation of hemopoietic cells, was found to be upregulated in the presen ce of the EBNA 3 protein family, but not in cells expressing the indiv idual 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 e xpressing cells as demonstrated by Northern blot, RT-PCR, and immunobl ot. In contrast to EBV-negative BL cells, pleckstrin RNA and protein w ere highly expressed in EBV growth transformed lymphoblastoid cell lin es which are thought to play an important role in EBV persistence in v ivo. These data suggest that induction of pleckstrin might be importan t for the EBV-controlled activation of cells and offers a unique biolo gical system for analyzing pleckstrin function. (C) 1996 Academic Pres s, Inc.