Characterization of the CD48 gene demonstrates a positive element that is specific to Epstein-Barr virus-immortalized B-cell lines and contains an essential NF-kappa B site.
Epstein-Barr virus (EBV) infection of mature, resting B cells drives them to become lymphoblasts expressing high levels of cell surface molecules, such as CD48, characteristically expressed on normal activated B cells. Here, we report on the identification of an enhancer element in the CD48 gene which reproducibly confers strong transcriptional activity only in EBV-positive B-lymphoblastoid cell lines. The element is not activated upon infection of established EBV-negative B-cell lines, indicating that EBV fails to drive these cells to a fully lymphoblastoid phenotype. An NF-kappa B binding site is an essential component of the element but alone is not sufficient to account for the activity or the specificity of the element. We have detected a specific nuclear protein complex that binds to the element and show that NF-kappa B1 (p50) is a part of this complex. The EBV-encoded latent membrane protein 1 is capable of transactivating the isolated CD48 NF-kappa B site but not the intact element, suggesting that the latent membrane protein 1-driven activation of NF-kappa B/Rel must interact with other regulatory pathways to control expression of cellular genes as EBV drives resting B cells into the cell cycle.
Klaman
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LD
Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111.
Thorley-Lawson
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DA
D015703:Antigens, CD / Q000235:genetics*; D001402:B-Lymphocytes / Q000821:virology*; D001483:Base Sequence; D000071178:CD48 Antigen; D002460:Cell Line; D002472:Cell Transformation, Viral; D003850:Deoxyribonuclease I / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D016328:NF-kappa B; D003850:Deoxyribonuclease I