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 (LMP1) 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 lymphoma, 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 important for the activation of the transcription factor NF-kappa B. These findings lead us to test whether these natural deletion variants may have a functional effect, We measured the stimulation of their activity using a luciferase reporter plasmid containing NF-kappa B responsive elements, We tested the NF-kappa B inducing activity of four naturally occurring LMP1 deletion variants, Our results show that these deletion variants activate NF-kappa B to the same level as the wildtype form, indicating that the crucial residues for NF-kappa B activation are conserved among the variants isolated and lie within the last 32 amino acids of the C-terminal domain of the LMP1 oncogene.