NF-KAPPA-B ONLY PARTIALLY MEDIATES EPSTEIN-BARR-VIRUS LATENT MEMBRANE-PROTEIN-1 ACTIVATION OF B-CELLS

The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is re quired for EBV-induced immortalization of human B cells and causes tum origenic transformation of cell lines. LMP1 expression induces phenoty pic changes resembling B cell activation, such as cell sire increase a nd up-regulation of cell surface activation markers. LMP1 contains two domains that activate the transcription factor NF-kappa B, one throug h interactions with TRAF proteins and the other with the TRADD protein . The purpose of the present study was to investigate the importance o f NF-kappa B induction in the up-regulation of the B cell activation m arkers ICAM-1 and CD71 by LMP1. This study shows that expression of LM P1 activates transcription from p50/p65- and c-Rel-responsive promoter s, and that this activity can be completely inhibited by expression of a dominant inhibitory I kappa B mutant. ICAM-1 and CD71 are neverthel ess upregulated by LMP1 in primary B cells and cell lines expressing t he dominant I kappa B. Furthermore, LMP1-induced cell size increase of primary B cells was unaffected by I kappa B expression. It was conclu ded that even when LMP1 is unable to activate NF-kappa B, it is still capable of inducing certain characteristics of activated B cells, stro ngly suggesting that LMP1 can also activate cells independently of NF- kappa B.