|
|
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.
 Previous Article | Next Article 
Submitted May 4, 2006
Accepted July 12, 2006
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*
GSF-Research Center for Environment and Health, Munchen, Germany
Friedrich-Alexander-University Erlangen, Erlangen, Germany
* Corresponding author; email: jungnickel{at}gsf.de.
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]
|
|
|
|
|
