Modulation of cellular gene expression in B lymphoma cells following in vitro infection by Epstein-Barr virus (EBV).
In vitro infection of EBV-negative lymphoma cell lines with immortalizing strains of Epstein-Barr virus induces the cell-surface expression of B-cell markers, such as the EBV receptor/CR2 (CD21) and the CD23 antigen. The non-immortalizing EBV variant, P3HRI, which carries a deletion encompassing the EBV nuclear antigen 2 (EBNA2) gene, fails to induce any such expression. We show here that the EBV-mediated up-regulation of cell-surface expression of these molecules is associated with an increased level of the specific steady-state RNA corresponding to these 2 genes. These results suggest that the role of EBNA2 in B-cell growth and immortalization may be related to its role in transactivation of cellular genes. In order to identify other cellular genes whose expression may be modulated by EBV, we analyzed the level of transcription of a set of genes possibly involved in Burkitt's lymphoma pathogenesis. The level of the c-myc oncogene transcript was not significantly affected by in vitro EBV infection. The c-fgr oncogene, thought to be specifically activated in EBV-infected cells, was found to be expressed in some EBV-negative lymphoma cells and also to be activated by both non-immortalizing and immortalizing strains of EBV. The expression of vimentin, the major 56-kDa polypeptide of mesenchymal cell intermediate filaments, was altered by all EBV isolates, in either a negative or a positive way, depending on the cell line. Expression of lymphocyte-function-associated antigens, LFA-1 alpha/beta (CD11 a/18) and LFA-3 (CD58), involved in intercellular adhesion and the T-cytotoxic pathway, were differentially regulated by EBV; a crucial observation was the activation by immortalizing EBV isolates of LFA-1 beta chain (CD18) and of LFA-3 (CD58). The EBV-and possibly EBNA2-associated modulation of cellular genes, such as CR2 (CD21), CD23 and LFAs, probably represents key events for EBV-induced B-cell proliferation, and also for in vivo immune control of EBV-infected B cells.
International Agency for Research on Cancer, Lyon, France.
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Calender
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Cordier
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Billaud
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Lenoir
D015703:Antigens, CD / Q000096:biosynthesis; D000954:Antigens, Surface / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000378:metabolism*; D015415:Biomarkers; D015152:Blotting, Northern; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism*; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D015967:Gene Expression Regulation, Viral; D016259:Genes, myc; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012313:RNA / Q000096:biosynthesis; D014158:Transcription, Genetic; D015854:Up-Regulation; D014746:Vimentin / Q000096:biosynthesis; D019061:src-Family Kinases
D015703:Antigens, CD; D000954:Antigens, Surface; D015415:Biomarkers; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D014746:Vimentin; D018799:Intercellular Adhesion Molecule-1; D012313:RNA; D011505:Protein-Tyrosine Kinases; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases