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Journal of Virology, November 2004, p. 12694-12697, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12694-12697.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

EBNA2 Is Required for Protection of Latently Epstein-Barr Virus-Infected B Cells against Specific Apoptotic Stimuli

Jae Myun Lee,1,{dagger} Kyoung-Ho Lee,2,{dagger},{ddagger} Christopher J. Farrell,3 Paul D. Ling,4 Bettina Kempkes,5 Jeon Han Park,1 and S. Diane Hayward2,3*

Department of Microbiology, Yonsei University, Seoul, Korea,1 The Sidney Kimmel Comprehensive Cancer Center,2 Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, Maryland,3 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas,4 Institute of Clinical Molecular Biology and Tumor Genetics, GSF-National Research Center for Environment and Health, Munich, Germany5

Received 1 April 2004/ Accepted 5 July 2004

In addition to functioning as a transcriptional transactivator, Epstein-Barr virus EBNA2 interacts with Nur77 to protect against Nur77-mediated apoptosis. Estrogen-regulated EBNA2 in EREB2-5 cells was replaced by either EBNA2 or EBNA2 with a deletion of conserved region 4 (EBNA2{Delta}CR4). Both EBNA2-converted and EBNA2{Delta}CR4-converted EREB2-5 cells grew in the absence of estrogen and expressed LMP1. Treatment with tumor necrosis factor alpha did not induce apoptosis of EBNA2- or EBNA2{Delta}CR4-expressing cells, but EBNA2{Delta}CR4 cells were susceptible to etoposide and 5-fluorouracil, Nur77-mediated inducers of apoptosis. Thus, EBNA2 protects B cells against specific apoptotic agents against which LMP1 is not effective.

* Corresponding author. Mailing address: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, School of Medicine, Bunting-Blaustein Building CRB308, 1650 Orleans St., Baltimore, MD 21231. Phone: (410) 614-0592. Fax: (410) 502-6802. E-mail: dhayward{at}jhmi.edu.

{dagger} These authors contributed equally.

{ddagger} Present address: Department of Microbiology, Wonju Yonsei University, Wonju, Korea.

Journal of Virology, November 2004, p. 12694-12697, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12694-12697.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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