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Cytostatic effect of Epstein-Barr virus latent membrane protein-1 analyzed using tetracycline-regulated expression in B cell lines.
Virology. 1996 Sep 01; 223(1):29-40.V

Abstract

Tetracycline-regulated vectors were used to obtain inducible expression in stable transfected B cell lines of two Epstein-Barr virus (EBV) latent genes, LMP1 and EBNA2. The transfected genes were tightly repressed by low, nontoxic concentrations of tetracycline (< or = 1 microgram/ml) and, following removal of tetracycline, were induced to levels comparable to or up to 3x that of EBV-transformed normal lymphoblastoid cell lines. In transfected DG75 cells, induced expression of LMP1, but not of EBNA2, led to the expected upregulation of various cell surface markers, including: CD40, CD54, CD58, and HLA class I.A novel observation was that both LMP1 and EBNA2 independently caused the downregulation of surface IgM, an effect mirrored in EBV-positive Burkitt lymphoma lines undergoing phenotypic drift during the transition from latency I to latency III in which both LMP1 and EBNA2 are upregulated. Most remarkably, induced LMP1 expression almost completely inhibited cell growth for 4 to 5 days, after which the cells recovered a limited proliferative capacity. The cytostatic effect of LMP1 was observed in all three B cell lines studied: DG75, BJAB, and Akata. Further analysis showed that induction of LMP1 coincided with a reduction in the levels of c-myc, and that the cytostatic effect was due to an accumulation of cells at the G2/M phase of the cell cycle. These data suggest a novel function for the LMP1 oncogene in controlling the proliferation of EBV-infected cells by regulating progress through G2/M phase.

Authors+Show Affiliations

Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8806537

Citation

Floettmann, J E., et al. "Cytostatic Effect of Epstein-Barr Virus Latent Membrane Protein-1 Analyzed Using Tetracycline-regulated Expression in B Cell Lines." Virology, vol. 223, no. 1, 1996, pp. 29-40.
Floettmann JE, Ward K, Rickinson AB, et al. Cytostatic effect of Epstein-Barr virus latent membrane protein-1 analyzed using tetracycline-regulated expression in B cell lines. Virology. 1996;223(1):29-40.
Floettmann, J. E., Ward, K., Rickinson, A. B., & Rowe, M. (1996). Cytostatic effect of Epstein-Barr virus latent membrane protein-1 analyzed using tetracycline-regulated expression in B cell lines. Virology, 223(1), 29-40.
Floettmann JE, et al. Cytostatic Effect of Epstein-Barr Virus Latent Membrane Protein-1 Analyzed Using Tetracycline-regulated Expression in B Cell Lines. Virology. 1996 Sep 1;223(1):29-40. PubMed PMID: 8806537.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytostatic effect of Epstein-Barr virus latent membrane protein-1 analyzed using tetracycline-regulated expression in B cell lines. AU - Floettmann,J E, AU - Ward,K, AU - Rickinson,A B, AU - Rowe,M, PY - 1996/9/1/pubmed PY - 1996/9/1/medline PY - 1996/9/1/entrez SP - 29 EP - 40 JF - Virology JO - Virology VL - 223 IS - 1 N2 - Tetracycline-regulated vectors were used to obtain inducible expression in stable transfected B cell lines of two Epstein-Barr virus (EBV) latent genes, LMP1 and EBNA2. The transfected genes were tightly repressed by low, nontoxic concentrations of tetracycline (< or = 1 microgram/ml) and, following removal of tetracycline, were induced to levels comparable to or up to 3x that of EBV-transformed normal lymphoblastoid cell lines. In transfected DG75 cells, induced expression of LMP1, but not of EBNA2, led to the expected upregulation of various cell surface markers, including: CD40, CD54, CD58, and HLA class I.A novel observation was that both LMP1 and EBNA2 independently caused the downregulation of surface IgM, an effect mirrored in EBV-positive Burkitt lymphoma lines undergoing phenotypic drift during the transition from latency I to latency III in which both LMP1 and EBNA2 are upregulated. Most remarkably, induced LMP1 expression almost completely inhibited cell growth for 4 to 5 days, after which the cells recovered a limited proliferative capacity. The cytostatic effect of LMP1 was observed in all three B cell lines studied: DG75, BJAB, and Akata. Further analysis showed that induction of LMP1 coincided with a reduction in the levels of c-myc, and that the cytostatic effect was due to an accumulation of cells at the G2/M phase of the cell cycle. These data suggest a novel function for the LMP1 oncogene in controlling the proliferation of EBV-infected cells by regulating progress through G2/M phase. SN - 0042-6822 UR - https://www.unboundmedicine.com/medline/citation/8806537/Cytostatic_effect_of_Epstein_Barr_virus_latent_membrane_protein_1_analyzed_using_tetracycline_regulated_expression_in_B_cell_lines_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(96)90452-3 DB - PRIME DP - Unbound Medicine ER -