Evidence map›Paper›PMID 27217538›Full record

ArticleThe Journal of experimental medicine2016

Epstein-Barr virus nuclear protein EBNA3C directly induces expression of AID and somatic mutations in B cells.

Jens S Kalchschmidt, Rachael Bashford-Rogers, Kostas Paschos, Adam C T Gillman, Christine T Styles, Paul Kellam, Martin J Allday

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
4.3field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 75 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Jens S KalchschmidtMolecular Virology, Department of Medicine, Imperial College London, London W2 1PG, England, UK.
Rachael Bashford-RogersWellcome Trust Sanger Institute, Cambridge CB10 1SA, England, UK.
Kostas PaschosMolecular Virology, Department of Medicine, Imperial College London, London W2 1PG, England, UK.
Adam C T GillmanMolecular Virology, Department of Medicine, Imperial College London, London W2 1PG, England, UK.
Christine T StylesMolecular Virology, Department of Medicine, Imperial College London, London W2 1PG, England, UK.
Paul KellamWellcome Trust Sanger Institute, Cambridge CB10 1SA, England, UK.
Martin J AlldayMolecular Virology, Department of Medicine, Imperial College London, London W2 1PG, England, UK m.allday@imperial.ac.uk.
Imperial College London · GBWellcome Sanger Institute · GB

Funding

Wellcome TrustWellcome Trust 097005Wellcome Trust 099273/Z/12/Z
6 · The paper itself

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.

Indexed as

AICDA (Activation-Induced Cytidine Deaminase)Burkitt LymphomaCell LineCytidine DeaminaseEpstein-Barr Virus Nuclear AntigensFemaleGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticGene Rearrangement, B-LymphocyteHerpesvirus 4, HumanHumansMaleNeoplasm ProteinsResponse ElementsSomatic Hypermutation, ImmunoglobulinAICDA (Activation-Induced Cytidine Deaminase)Cytidine DeaminaseEBNA-3C, epstein-barr virusEpstein-Barr Virus Nuclear AntigensNeoplasm Proteins

Identifiers

PMID27217538
PMCPMC4886369
OpenAlexW2406676791

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.