Abstract
The Epstein-Barr virus (EBV) encoded Latent Membrane Protein 1 (LMP1) has been shown to increase the expression of promyelocytic leukemia protein (PML) and the immunofluorescent intensity of promyelocytic leukemia nuclear bodies (PML NBs). PML NBs have been implicated in the modulation of transcription and the association of reporter plasmids with PML NBs has been implicated in repression of reporter activity. Additionally, repression of various reporters in the presence of LMP1 has been noted. This study demonstrates that LMP1 suppresses expression of reporter activity in a dose responsive manner and corresponds with the LMP1 induced increase in PML NB intensity. Disruption of PML NBs with arsenic trioxide or a PML siRNA restores reporter activity. These data offer an explanation for previously conflicting data on LMP1 signaling and calls attention to the possibility of false-positives and false-negatives when using reporter assays as a research tool in cells expressing LMP1.
MeSH terms
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Arsenic Trioxide
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Arsenicals / pharmacology
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Cell Line
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Dose-Response Relationship, Drug
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Epstein-Barr Virus Infections / complications
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Epstein-Barr Virus Infections / genetics
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Epstein-Barr Virus Infections / metabolism*
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Epstein-Barr Virus Infections / virology
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Gene Expression Regulation, Leukemic / drug effects*
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Gene Expression Regulation, Viral / drug effects*
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Gene Silencing / drug effects
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Genes, Reporter
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Herpesvirus 4, Human / genetics
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Herpesvirus 4, Human / metabolism*
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Humans
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Intranuclear Inclusion Bodies / genetics
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Intranuclear Inclusion Bodies / metabolism
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Leukemia, Promyelocytic, Acute / complications
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Leukemia, Promyelocytic, Acute / genetics
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Leukemia, Promyelocytic, Acute / metabolism*
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Leukemia, Promyelocytic, Acute / virology
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Luciferases / analysis
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Nuclear Proteins / antagonists & inhibitors*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Oxides / pharmacology
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Plasmids / genetics
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Plasmids / pharmacology*
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Promyelocytic Leukemia Protein
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RNA, Small Interfering / pharmacology
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Transcription Factors / antagonists & inhibitors*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription, Genetic / drug effects
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Transfection
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Tumor Suppressor Proteins / antagonists & inhibitors*
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
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Viral Matrix Proteins / genetics
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Viral Matrix Proteins / metabolism*
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beta-Galactosidase / analysis
Substances
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Arsenicals
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EBV-associated membrane antigen, Epstein-Barr virus
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Nuclear Proteins
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Oxides
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Promyelocytic Leukemia Protein
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RNA, Small Interfering
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Transcription Factors
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Tumor Suppressor Proteins
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Viral Matrix Proteins
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PML protein, human
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Luciferases
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beta-Galactosidase
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Arsenic Trioxide