Abstract
The principal Epstein-Barr virus (EBV) oncoprotein, Latent Membrane Protein 1 (LMP1), is expressed in most EBV-associated human malignancies. LMP1 mimics CD40 receptor signaling to provide infected cells with constitutive NF-κB, MAP kinase, IRF7, and PI3 kinase pathway stimulation. EBV-transformed B-cells are particularly dependent on constitutive NF-κB activity, and rapidly undergo apoptosis upon NF-κB blockade. Here, we review LMP1 function, with special attention to current understanding of the molecular mechanisms of LMP1-mediated NF-κB and IRF7 pathway activation. Recent advances include the elucidation of transmembrane motifs important for LMP1 trafficking and ligand-independent signaling, analysis of genome-wide LMP1 gene targets, and the identification of novel cell proteins that mediate LMP1 NF-κB and IRF7 pathway activation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Cell Transformation, Viral
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Herpesvirus 4, Human / immunology*
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Herpesvirus 4, Human / pathogenicity
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Host-Pathogen Interactions*
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Humans
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Interferon Regulatory Factor-7 / immunology*
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NF-kappa B / immunology*
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Signal Transduction*
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Viral Matrix Proteins / immunology*
Substances
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EBV-associated membrane antigen, Epstein-Barr virus
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IRF7 protein, human
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Interferon Regulatory Factor-7
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NF-kappa B
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Viral Matrix Proteins