Epstein-barr virus transformation: involvement of latent membrane protein 1-mediated activation of NF-kappaB

Oncogene. 1999 Nov 22;18(49):6959-64. doi: 10.1038/sj.onc.1203217.


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-kappaB. Mutants rendering LMP1 defective in these protein interactions are impaired in their abilities to activate NF-kappaB in reporter gene assays. Concordantly, EBV recombinants with LMP1 mutations that are compromised for NF-kappaB activation are impaired for growth transformation. Thus, EBV-mediated growth transformation is genetically and biochemically linked to LMP1-mediated activation of NF-kappaB.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Apoptosis
  • B-Lymphocytes / pathology
  • Cell Transformation, Viral*
  • DNA-Binding Proteins / physiology
  • Herpesvirus 4, Human / genetics*
  • Humans
  • I-kappa B Proteins*
  • Lymphocyte Activation
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / physiology*
  • Proteins / physiology
  • Receptors, Tumor Necrosis Factor / physiology
  • TNF Receptor-Associated Factor 1
  • Viral Matrix Proteins / physiology*


  • DNA-Binding Proteins
  • EBV-associated membrane antigen, Epstein-Barr virus
  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • TNF Receptor-Associated Factor 1
  • Viral Matrix Proteins
  • NF-KappaB Inhibitor alpha