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

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Abstract
Epstein-Barr virus (EBV) transforms resting primary human B lymphocytes into indefinitely proliferating lymphoblastoid cell lines in vitro and is associated with several human malignancies in vivo. Recombinant EBV genetic analyses combined with in vitro B lymphocyte transformation assays demonstrate that latent infection membrane protein 1 (LMP1) is essential for EBV-mediated lymphocyte transformation. LMP1 has no intrinsic enzymatic activity but instead aggregates cellular proteins of the tumor necrosis factor receptor signaling pathway to activate transcription factor NF-κB. Mutants rendering LMP1 defective in these protein interactions are impaired in their abilities to activate NF-κB in reporter gene assays. Concordantly, EBV recombinants with LMP1 mutations that are compromised for NF-κB activation are impaired for growth transformation. Thus, EBV-mediated growth transformation is genetically and biochemically linked to LMP1-mediated activation of NF-κB.