| Epstein-Barr virus nuclear antigen 2 inhibits AID expression during EBV-driven B-cell growth. | |
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MedLine Citation:
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PMID: 16882707 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Stephanie Tobollik; Linda Meyer; Maike Buettner; Sandra Klemmer; Bettina Kempkes; Elisabeth Kremmer; Gerald Niedobitek; Berit Jungnickel |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-08-01 |
Journal Detail:
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Title: Blood Volume: 108 ISSN: 0006-4971 ISO Abbreviation: Blood Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2006-11-20 Completed Date: 2007-01-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 3859-64 Citation Subset: AIM; IM |
Affiliation:
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Institute of Clinical and Molecular Biology, GSF-Research Center for Environment and Health, Marchioninistrasse 25, 81377 München, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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B-Lymphocytes
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immunology*,
pathology,
virology Cell Line, Tumor Cell Transformation, Viral / immunology* Cytidine Deaminase / genetics, immunology* Epstein-Barr Virus Infections / genetics, immunology*, pathology Epstein-Barr Virus Nuclear Antigens / genetics, immunology* Gene Expression Regulation, Enzymologic / immunology* Genome, Viral / immunology Herpesvirus 4, Human / genetics, immunology* Humans Somatic Hypermutation, Immunoglobulin / immunology Viral Matrix Proteins / immunology Viral Proteins / genetics, immunology* Virus Activation / immunology |
| Chemical | |
Reg. No./Substance:
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0/EBNA-2 protein, Human herpesvirus 4; 0/EBV-associated membrane antigen, Epstein-Barr virus; 0/Epstein-Barr Virus Nuclear Antigens; 0/Viral Matrix Proteins; 0/Viral Proteins; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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