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Epstein–Barr virus latent membrane protein-1 activates CD25 expression in lymphoma cells involving the NFκB pathway

Abstract

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) α-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 NFκB enhancement by a constitutive repressive form of IκB-α resulted in decreased CD25 surface expression, indicating that NFκB 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.

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Acknowledgements

We thank Dr Sigrun Smola for critical reading of the manuscript.

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Correspondence to M Vockerodt.

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This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB502/P5 and KU954/4–1).

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Vockerodt, M., Tesch, H. & Kube, D. Epstein–Barr virus latent membrane protein-1 activates CD25 expression in lymphoma cells involving the NFκB pathway. Genes Immun 2, 433–441 (2001). https://doi.org/10.1038/sj.gene.6363803

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