1887

Abstract

The latent membrane protein 1 (LMP1) of Epstein- Barr virus (EBV) is required for EBV-induced immortalization of human B cells and causes tumori- genic transformation of cell lines. LMP1 expression induces phenotypic changes resembling B cell activation, such as cell size increase and up-regulation of cell surface activation markers. LMP1 contains two domains that activate the transcription factor NF-κB, one through interactions with TRAF proteins and the other with the TRADD protein. The purpose of the present study was to investigate the importance of NF-κB induction in the up-regulation of the B cell activation markers ICAM-1 andCD71 byLMP1. This study shows that expression of LMP1 activates transcription from p50/p65- and c-Rel-responsive promoters, and that this activity can be completely inhibited by expression of a dominant inhibitory IκB mutant. ICAM-1 and CD71 are nevertheless up- regulated by LMP1 in primary B cells and cell lines expressing the dominant IκB. Furthermore, LMP1- induced cell size increase of primary B cells was unaffected by IκB expression. It was concluded that even when LMP1 is unable to activate NF-κB, it is still capable of inducing certain characteristics of activated B cells, strongly suggesting that LMP1 can also activate cells independently of NF-κB.

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1998-09-01
2022-08-11
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