Epstein-Barr virus latent membrane protein-1 activates CD25 expression in lymphoma cells involving the NFkappaB pathway.
Epstein-Barr virus (EBV) is associated with several human malignancies including Burkitt's lymphoma (BL), Hodgkin's disease (HD) and nasopharyngeal carcinoma. A variety of cytokines and receptors have been described to be activated by EBV. Here we show that the IL-2 receptor (IL-2R) alpha-chain, which is weakly expressed on normal resting lymphoid cells, is activated by EBV. Comparison of EBV-negative BL cell lines and their EBV convertants showed an enhanced CD25 expression in EBV-positive BL cells. Transient expression of the oncogenic virus protein latent membrane protein-1 (LMP1) in L428 Hodgkin's lymphoma cells and in Burkitt's lymphoma cells (BL2, BL41, BL30) cells leads to enhanced CD25 expression. Both C-terminal activating regions (CTARs) of LMP1 are involved in CD25 activation. Inhibition of LMP1-mediated NFkappaB enhancement by a constitutive repressive form of IkappaB-alpha resulted in decreased CD25 surface expression, indicating that NFkappaB is involved in CD25 gene regulation. Furthermore, LMP1-mediated CD25 activation was associated with enhanced levels of the soluble form of CD25 (sCD25) in L428 Hodgkin's lymphoma cells but not in BL cells. LMP1 associated enhanced expression of membrane CD25 and soluble CD25 may have immunomodulatory functions and could be involved in biology of EBV-associated diseases.
Vockerodt
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M
Klinik für Innere Medizin I, Zentrum für Molekulare Medizin der Universität zu Köln, D-50924 Köln, Germany. Martina.Vockerodt@medizin.uni-koel.de
Tesch
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H
Kube
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D000954:Antigens, Surface / Q000096:biosynthesis; D002051:Burkitt Lymphoma / Q000378:metabolism / Q000821:virology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000503:physiopathology; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006689:Hodgkin Disease / Q000378:metabolism / Q000821:virology*; D006801:Humans; D020672:I-kappa B Proteins; D008223:Lymphoma; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000502:physiology; D017434:Protein Structure, Tertiary; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D012995:Solubility; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000502:physiology*
D000954:Antigens, Surface; D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D009856:Oncogene Proteins, Viral; D015375:Receptors, Interleukin-2; D014763:Viral Matrix Proteins; D000072000:NF-KappaB Inhibitor alpha