NATURAL 30 BASE-PAIR AND 69 BASE-PAIR DELETION VARIANTS OF THE LMP1 ONCOGENE DO STIMULATE NF-KAPPA-B-MEDIATED TRANSCRIPTION

An increasing number of reports shows a link between the Epstein-Barr virus (EBV) and lymphoid neoplasia. The latent membrane protein 1 (LMP 1) is likely to play a determinant role in this process since this EBV encoded protein has oncogenic properties and is usually expressed in EBV-associated lymphoproliferative diseases (LPD), except Burkitt's ly mphoma, We previously identified in LPD patients mutational hot spots and a 30 bp or 69 bp deletion in the LMP1 gene region coding for the C -terminal domain, These deletions are located in an area shown to be i mportant for the activation of the transcription factor NF-kappa B. Th ese findings lead us to test whether these natural deletion variants m ay have a functional effect, We measured the stimulation of their acti vity using a luciferase reporter plasmid containing NF-kappa B respons ive elements, We tested the NF-kappa B inducing activity of four natur ally occurring LMP1 deletion variants, Our results show that these del etion variants activate NF-kappa B to the same level as the wildtype f orm, indicating that the crucial residues for NF-kappa B activation ar e conserved among the variants isolated and lie within the last 32 ami no acids of the C-terminal domain of the LMP1 oncogene.