Evidence map›Paper›PMID 25853421›Full record

ArticlePloS one2015

EBNA2 binds to genomic intervals associated with multiple sclerosis and overlaps with vitamin D receptor occupancy.

Vito A G Ricigliano, Adam E Handel, Geir K Sandve, Viviana Annibali, Giovanni Ristori, Rosella Mechelli, M Zameel Cader, Marco Salvetti

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

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.0field-weighted citation impact, top 22% 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

32 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. A disease-specific convergence of host and Epstein-Barr virus genetics in multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Article
  6. Immune Modulatory Effects of Vitamin D on Herpesvirus Infections.International journal of molecular sciences · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. The immunology of multiple sclerosis.Nature reviews. Immunology · 2022
    Review
  16. Article
  17. Article
  18. Antibodies from Multiple Sclerosis Brain Identified Epstein-Barr Virus Nuclear Antigen 1 & 2 Epitopes which Are Recognized by Oligoclonal Bands.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021
    Article
  19. Review
  20. Article
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

8 authors at 4 institutions in 3 countries.

Vito A G RiciglianoNuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; Neuroimmunology Unit, Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Adam E HandelMedical Research Council Functional Genomics Unit and Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom; Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom.
Geir K SandveDepartment of Informatics, University of Oslo, Blindern, Norway.
Viviana AnnibaliCentre for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Rome, Italy.
Giovanni RistoriCentre for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Rome, Italy.
Rosella MechelliCentre for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Rome, Italy.
M Zameel CaderNuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
Marco SalvettiCentre for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Rome, Italy.
Sapienza University of Rome · ITJohn Radcliffe Hospital · GBUniversity of Oslo · NOUniversity of Oxford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epstein-Barr virus (EBV) is a non-heritable factor that associates with multiple sclerosis (MS). However its causal relationship with the disease is still unclear. The virus establishes a complex co-existence with the host that includes regulatory influences on gene expression. Hence, if EBV contributes to the pathogenesis of MS it may do so by interacting with disease predisposing genes. To verify this hypothesis we evaluated EBV nuclear antigen 2 (EBNA2, a protein that recent works by our and other groups have implicated in disease development) binding inside MS associated genomic intervals. We found that EBNA2 binding occurs within MS susceptibility sites more than expected by chance (factor of observed vs expected overlap [O/E] = 5.392-fold, p < 2.0e-05). This remains significant after controlling for multiple genomic confounders. We then asked whether this observation is significant per se or should also be viewed in the context of other disease relevant gene-environment interactions, such as those attributable to vitamin D. We therefore verified the overlap between EBNA2 genomic occupancy and vitamin D receptor (VDR) binding sites. EBNA2 shows a striking overlap with VDR binding sites (O/E = 96.16-fold, p < 2.0e-05), even after controlling for the chromatin accessibility state of shared regions (p <0.001). Furthermore, MS susceptibility regions are preferentially targeted by both EBNA2 and VDR than by EBNA2 alone (enrichment difference = 1.722-fold, p = 0.0267). Taken together, these findings demonstrate that EBV participates in the gene-environment interactions that predispose to MS.

Indexed as

Epstein-Barr Virus Nuclear AntigensGenome, HumanHumansMultiple SclerosisPolymorphism, Single NucleotideProtein BindingProtein TransportReceptors, CalcitriolEpstein-Barr Virus Nuclear AntigensReceptors, Calcitriol

Identifiers

PMID25853421
PMCPMC4390304
OpenAlexW2028778538

What OpenQuestion holds

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LicenceCC BY
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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.