Epstein-Barr Virus Antagonizes The Antiproliferative Activity Of Transforming Growth Factor-Beta But Does Not Abolish Its Signaling

TGF-beta induces apoptosis and inhibits the proliferation of EBV-negative B-lymphoma cell lines. In contrast, EBV-immortalized B cells are resistant to both the proapoptotic and the antiproliferative activities of TGF-beta. We have generated a lymphoblastoid cell line, in which we can switch on and off the EBV-specific transcriptional program driven by EBNA2. When these cells express the EBNA2-driven phenotype, they are resistant to TGF-beta-mediated growth arrest. We used this cell line to readdress the question of how EBV can overcome the antiproliferative TGF-beta activity. We show here that EBV-driven cells remain TGF-beta-responsive since TGF-beta target genes are readily induced. Thus, EBV can overcome TGF-beta- mediated growth arrest without interfering with the core machinery of the TGF-beta signaling pathway, which links ligand binding to the induction of TGF-beta target genes. (C) 2002 Wiley-Liss, Inc.