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Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes

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Abstract

Epstein-Barr virus (EBV) is a human gamma herpes virus that infects B cells and induces their transformation into immortalized lymphoblasts that can grow as cell lines (LCLs) in vitro. EBNA-3 is a member of the EBNA-3-protein family that can regulate transcription of cellular and viral genes. The identification of EBNA-3 cellular partners and a study of its influence on cellular pathways are important for understanding the transforming action of the virus. In this work, we have identified the vitamin D receptor (VDR) protein as a binding partner of EBNA-3. We found that EBNA3 blocks the activation of VDR-dependent genes and protects LCLs against vitamin-D3-induced growth arrest and/or apoptosis. The presented data shed some light on the anti-apoptotic EBV program and the role of the EBNA-3-VDR interaction in the viral strategy.

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Acknowledgments

This work was supported by the Swedish Cancer Society, a matching grant from the Concern Foundation (Los Angeles), the Cancer Research Institute (New York), the Swedish Institute, and the Swedish Foundation for Strategic Research.

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Author notes

  1. Surya Pavan Yenamandra

    Present address: Bioinformatics Institute, 30 Biopolis Street, No. 07-01, 138671, Matrix, Singapore

Authors and Affiliations

  1. Department of Microbiology, Tumor, and Cell Biology (MTC), Karolinska Institute, 171 77, Stockholm, Sweden

    Surya Pavan Yenamandra, Suhas Deoram Darekar, George Klein & Elena Kashuba

  2. Ludwig Institute for Cancer Research, Uppsala Branch, 751 24, Uppsala, Sweden

    Ulf Hellman

  3. Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Center for Environmental Health, 81377, Munich, Germany

    Bettina Kempkes & Sabine Petermann

  4. Queensland Institute for Medical Research, Brisbane, QLD, 4029, Australia

    Tom Sculley

  5. R. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, 03022, Kyiv, Ukraine

    Elena Kashuba

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  1. Surya Pavan Yenamandra
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  2. Ulf Hellman
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Correspondence to Elena Kashuba.

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Yenamandra, S.P., Hellman, U., Kempkes, B. et al. Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes. Cell. Mol. Life Sci. 67, 4249–4256 (2010). https://doi.org/10.1007/s00018-010-0441-4

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  • DOI: https://doi.org/10.1007/s00018-010-0441-4

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