Epstein-Barr virus transformation: involvement of latent membrane protein 1-mediated activation of NF-kappa B

Epstein-Barr virus (EBV) transforms resting primary human B lymphocytes int o indefinitely proliferating lymphoblastoid cell lines irt vitro and is ass ociated with several human malignancies ill vivo. Recombinant EBV genetic a nalyses combined with in vitro B lymphocyte transformation assays demonstra te that latent infection membrane protein 1 (LMP1) is essential for EBV-med iated lymphocyte transformation. LMP1 has no intrinsic enzymatic activity b ut instead aggregates cellular proteins of the tumor necrosis factor recept or signaling pathway to activate transcription factor NF-kappa B. Mutants r endering LMP1 defective in these protein interactions are impaired in their abilities to activate NF-kappa B in reporter gene assays. Concordantly, EB V recombinants with LMP1 mutations that are compromised for NF-kappa B acti vation are impaired for growth transformation. Thus, EBV-mediated growth tr ansformation is genetically and biochemically linked to LMP1-mediated activ ation of NF-kappa B.