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Epstein-Barr virus nuclear antigen 2 inhibits AID expression during EBV-driven B-cell growth.
Blood. 2006 Dec 01; 108(12):3859-64.Blood

Abstract

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.

Authors+Show Affiliations

Institute of Clinical and Molecular Biology, GSF-Research Center for Environment and Health, Marchioninistrasse 25, 81377 München, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16882707

Citation

Tobollik, Stephanie, et al. "Epstein-Barr Virus Nuclear Antigen 2 Inhibits AID Expression During EBV-driven B-cell Growth." Blood, vol. 108, no. 12, 2006, pp. 3859-64.
Tobollik S, Meyer L, Buettner M, et al. Epstein-Barr virus nuclear antigen 2 inhibits AID expression during EBV-driven B-cell growth. Blood. 2006;108(12):3859-64.
Tobollik, S., Meyer, L., Buettner, M., Klemmer, S., Kempkes, B., Kremmer, E., Niedobitek, G., & Jungnickel, B. (2006). Epstein-Barr virus nuclear antigen 2 inhibits AID expression during EBV-driven B-cell growth. Blood, 108(12), 3859-64.
Tobollik S, et al. Epstein-Barr Virus Nuclear Antigen 2 Inhibits AID Expression During EBV-driven B-cell Growth. Blood. 2006 Dec 1;108(12):3859-64. PubMed PMID: 16882707.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epstein-Barr virus nuclear antigen 2 inhibits AID expression during EBV-driven B-cell growth. AU - Tobollik,Stephanie, AU - Meyer,Linda, AU - Buettner,Maike, AU - Klemmer,Sandra, AU - Kempkes,Bettina, AU - Kremmer,Elisabeth, AU - Niedobitek,Gerald, AU - Jungnickel,Berit, Y1 - 2006/08/01/ PY - 2006/8/3/pubmed PY - 2007/1/5/medline PY - 2006/8/3/entrez SP - 3859 EP - 64 JF - Blood JO - Blood VL - 108 IS - 12 N2 - 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. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/16882707/Epstein_Barr_virus_nuclear_antigen_2_inhibits_AID_expression_during_EBV_driven_B_cell_growth_ L2 - https://ashpublications.org/blood/article-lookup/doi/10.1182/blood-2006-05-021303 DB - PRIME DP - Unbound Medicine ER -