LATENT MEMBRANE-PROTEIN-1 OF EPSTEIN-BARR-VIRUS MIMICS A CONSTITUTIVELY ACTIVE RECEPTOR MOLECULE

Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is an int egral membrane protein which has transforming potential and is necessa ry but not sufficient for B-cell immortalization by EBV, LMP1 molecule s aggregate in the plasma membrane and recruit tumour necrosis factor receptor (TNF-R)-associated factors (TRAFs) which are presumably invol ved in the signalling cascade leading to NF-kappa B activation by LMP1 . Comparable activities are mediated by CD40 and other members of the TNF-R family, which implies that LMP1 could function as a receptor, LM P1 lacks extended extracellular domains similar to P-adrenergic recept ors but, in contrast, it also lacks any motifs involved in ligand bind ing, By using LMP1 mutants which can be oligomerized at will, we show that the function of LMP1 in 293 cells and B cells is solely dependent on oligomerization of its carboxy-terminus, Biochemically, oligomeriz ation is an intrinsic property of the transmembrane domain of wild-typ e LMP1 and causes a constitutive phenotype which can be conferred to t he signalling domains of CD40 or the TNF-2 receptor, In EBV, immortali zed B cells crosslinking in conjunction with membrane targeting of the carboxy-terminal signalling domain of LMP1 is sufficient for its biol ogical activities, Thus, LMP1 acts like a constitutively activated rec eptor whose biological activities are ligand-independent.