Epstein-barr virus transformation: involvement of latent membrane protein 1-mediated activation of NF-kappaB.
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.
Cahir McFarland
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Brigham and Women's Hospital, Department of Medicine, 181 Longwood Avenue, Boston, Massachusetts, MA 02115, USA.
Izumi
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Mosialos
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D017209:Apoptosis; D001402:B-Lymphocytes / Q000473:pathology; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D020672:I-kappa B Proteins; D008213:Lymphocyte Activation; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000502:physiology*; D011506:Proteins / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D047990:TNF Receptor-Associated Factor 1; D014763:Viral Matrix Proteins / Q000502:physiology*
D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047990:TNF Receptor-Associated Factor 1; D014763:Viral Matrix Proteins; D000072000:NF-KappaB Inhibitor alpha