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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3859-3864. Prepublished online as a Blood First Edition Paper on August 1, 2006; DOI 10.1182/blood-2006-05-021303. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-021303v1 108/12/3859    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tobollik, S. Articles by Jungnickel, B. Search for Related Content PubMed PubMed Citation Articles by Tobollik, S. Articles by Jungnickel, B. Related Collections Immunobiology Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Epstein-Barr virus nuclear antigen 2 inhibits AID expression during EBV-driven B-cell growth Stephanie Tobollik, Linda Meyer, Maike Buettner, Sandra Klemmer, Bettina Kempkes, Elisabeth Kremmer, Gerald Niedobitek, and Berit Jungnickel From the Institute of Clinical and Molecular Biology and the Institute of Molecular Immunology, GSF–Research Center for Environment and Health, Munich; and the Institute of Pathology, Friedrich-Alexander-University, Erlangen, Germany. Somatic hypermutation and class-switch recombination in germinal centers critically depend on activation-induced cytidine deaminase (AID). Deregulation of AID may lead to the aberrant activation or persistence of both genetic processes, thus contributing to the pathogenesis of B-cell lymphomas by mistargeted mutagenesis or recombination. The Epstein-Barr virus (EBV) establishes an asymptomatic latent infection in more than 90% of the human population, but it has also been linked to lymphomagenesis. A cooperative relationship of EBV and the germinal center reaction during the establishment of viral persistence has been postulated, but the contribution of EBV latent genes to the respective genetic events remains to be investigated in detail. In the present study, we show that activation of the EBV growth program has a clear inhibitory effect on AID expression, due to a negative effect of the master transcription factor of this program, EBNA2. This mechanism may counterbalance AID induction by the LMP1 protein, in order to prevent deleterious genetic changes during EBV-induced B-cell growth. EBNA2-mediated AID inhibition also provides a molecular explanation for the previously observed differences in somatic hypermutation activity in EBV-associated lymphoproliferative diseases, thus pointing to a crucial mechanism of EBV-mediated regulation of genomic integrity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Machida, Y. Kondo, J. Y. Huang, Y.-C. Chen, K. T.-H. Cheng, Z. Keck, S. Foung, J. Dubuisson, V. M.-H. Sung, and M. M. C. Lai Hepatitis C Virus (HCV)-Induced Immunoglobulin Hypermutation Reduces the Affinity and Neutralizing Activities of Antibodies against HCV Envelope Protein J. Virol., July 1, 2008; 82(13): 6711 - 6720. [Abstract] [Full Text] [PDF] P. Perez-Duran, V. G. de Yebenes, and A. R. Ramiro Oncogenic events triggered by AID, the adverse effect of antibody diversification Carcinogenesis, December 1, 2007; 28(12): 2427 - 2433. [Abstract] [Full Text] [PDF] E. E. Crouch, Z. Li, M. Takizawa, S. Fichtner-Feigl, P. Gourzi, C. Montano, L. Feigenbaum, P. Wilson, S. Janz, F. N. Papavasiliou, et al. Regulation of AID expression in the immune response J. Exp. Med., May 14, 2007; 204(5): 1145 - 1156. [Abstract] [Full Text] [PDF] F. Boccellato, E. Anastasiadou, P. Rosato, B. Kempkes, L. Frati, A. Faggioni, and P. Trivedi EBNA2 Interferes with the Germinal Center Phenotype by Downregulating BCL6 and TCL1 in Non-Hodgkin's Lymphoma Cells J. Virol., March 1, 2007; 81(5): 2274 - 2282. [Abstract] [Full Text] [PDF] P. Gourzi, T. Leonova, and F. N. Papavasiliou Viral induction of AID is independent of the interferon and the Toll-like receptor signaling pathways but requires NF-{kappa}B J. Exp. Med., February 19, 2007; 204(2): 259 - 265. [Abstract] [Full Text] [PDF]

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