Epstein-Barr virus encoded EBNA-3 binds to vitamin D receptor and blocks activation of its target genes.
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.
Yenamandra
Surya Pavan
SP
Department of Microbiology, Tumor, and Cell Biology (MTC), Karolinska Institute, 171 77, Stockholm, Sweden.
Hellman
Ulf
U
Kempkes
Bettina
B
Darekar
Suhas Deoram
SD
Petermann
Sabine
S
Sculley
Tom
T
Klein
George
G
Kashuba
Elena
E
D000818:Animals; D002112:Calcifediol / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology; D013058:Mass Spectrometry; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*
D019309:Epstein-Barr Virus Nuclear Antigens; D018167:Receptors, Calcitriol; D002112:Calcifediol