Journal article
Epstein-Barr virus nuclear protein EBNA3C directly induces expression of AID and somatic mutations in B cells
- Abstract:
- Activation-induced cytidine deaminase (AID), the enzyme responsible for induction of sequence variation in immunoglobulins (Igs) during the process of somatic hypermutation (SHM) and also Ig class switching, can have a potent mutator phenotype in the development of lymphoma. Using various Epstein-Barr virus (EBV) recombinants, we provide definitive evidence that the viral nuclear protein EBNA3C is essential in EBV-infected primary B cells for the induction of AID mRNA and protein. Using lymphoblastoid cell lines (LCLs) established with EBV recombinants conditional for EBNA3C function, this was confirmed, and it was shown that transactivation of the AID gene (AICDA) is associated with EBNA3C binding to highly conserved regulatory elements located proximal to and upstream of the AICDA transcription start site. EBNA3C binding initiated epigenetic changes to chromatin at specific sites across the AICDA locus. Deep sequencing of cDNA corresponding to the IgH V-D-J region from the conditional LCL was used to formally show that SHM is activated by functional EBNA3C and induction of AID. These data, showing the direct targeting and induction of functional AID by EBNA3C, suggest a novel role for EBV in the etiology of B cell cancers, including endemic Burkitt lymphoma.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 1.6MB, Terms of use)
-
- Publisher copy:
- 10.1084/jem.20160120
Authors
- Publisher:
- Rockefeller University Press
- Journal:
- Journal of Experimental Medicine More from this journal
- Volume:
- 213
- Issue:
- 6
- Pages:
- 921-928
- Publication date:
- 2016-05-23
- Acceptance date:
- 2016-04-12
- DOI:
- EISSN:
-
1540-9538
- ISSN:
-
0022-1007
- Pmid:
-
27217538
- Language:
-
English
- Keywords:
- Pubs id:
-
pubs:927539
- UUID:
-
uuid:abe74172-258d-4466-9c1b-d2d1469c001f
- Local pid:
-
pubs:927539
- Source identifiers:
-
927539
- Deposit date:
-
2019-05-08
Terms of use
- Copyright holder:
- Kalchschmidt et al
- Copyright date:
- 2016
- Notes:
- © 2016 Kalchschmidt et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record