Antisense to the Epstein-Barr Virus (EBV)-Encoded Latent Membrane Protein 1 (LMP-1) Suppresses LMP-1 and Bcl-2 Expression and Promotes Apoptosis in EBV-Immortalized B Cells

作者: Jamie L. Kenney , Mary E. Guinness , Tyler Curiel , Jill Lacy

DOI: 10.1182/BLOOD.V92.5.1721

关键词: VirusBiologyCancer researchCell cultureMembrane proteinDownregulation and upregulationEpstein–Barr virusApoptosisViral matrix proteinViral transformation

摘要: The Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP-1) is required for viral transformation and functions to protect cells from apoptotic cell death, in part, by induction of antiapoptotic genes, including Bcl-2 A20. We have used antisense oligodeoxynucleotides targeted LMP-1 as a strategy suppress expression thereby inhibit its functions. shown that levels EBV-positive lymphoblastoid lines can be reduced vitro treatment with unmodified the first five codons open-reading frame. Furthermore, suppression was associated molecular phenotypic effects included downregulation LMP-1-inducible Mcl-1, inhibition proliferation, stimulation apoptosis, enhancement sensitivity chemotherapeutic agent, etoposide. These were largely sequence-specific observed EBV-positive, but not EBV-negative lines. studies suggest lowering EBV-associated malignancy might therapeutic synergize other antitumor agents.

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