Chimeric and Mutated Variants of LMP1

Abstract

Epstein Barr virus (EBV) efficiently immortalizes human B cells in vitro generating lymphoblastoid cell lines (LCL) with indefinite lifespan. Latent membrane protein 1 (LMP1) belongs to a set of nine viral proteins expressed in vitro, five of which appear to be essential for B-cell immortalization (for review, see ref. 1). LMP1 is a membrane protein composed of a short cytoplasmic aminoterminus (24 residues), a transmembrane domain with six membrane-spanning segments separated by short reverse turns and a long cytoplasmic carboxy terminus (200 residues; see Fig. 1) (2–4). Genetic analysis has shown that LMP1 is indispensable but not sufficient for B-cell immortalization (5–7). In the last years the hypothesis was raised that LMP1 might act as a constitutively active receptor because it integrates into the plasma membrane and patches as an oligomer (3,8). This idea was further supported by LMP1’s ability to bind molecules involved in the signaling cascade of the TNF-receptor family members (9–12). In analogy to known receptors such as CD40 or TNF-R2, LMP1 activates cellular transcription factors of the NFкB and AP-1 family (13–15). Transcriptional activation of target genes is supposed to play a key role in EBV-mediated immortalization as well as LMP1-mediated oncogenicity.