Evidence map›Paper›PMID 29394264›Full record

ArticlePloS one2018

Epstein-Barr virus is present in the brain of most cases of multiple sclerosis and may engage more than just B cells.

Asma Hassani, John R Corboy, Suhail Al-Salam, Gulfaraz Khan

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed
10.5field-weighted citation impact, top 1% 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

90 citing papers in PubMed, 152 citations in OpenAlex.

  1. Review
  2. Sequence Variation of Epstein-Barr Virus EBNA-1 Gene in Central Nervous System Inflammatory Demyelinating Diseases in Pakistan.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
    Article
  3. Review
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  8. Article
  9. Review
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  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Multiple sclerosis and infection: history, EBV, and the search for mechanism.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  18. Epstein-Barr virus and the immune microenvironment in multiple sclerosis: Insights from high-dimensional brain tissue imaging.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Article
  20. Editorial: Viral infection pathogenesis and pathology in nervous system.Frontiers in cellular and infection microbiology · 2025
    Article

30 more citing papers are in PubMed but not listed here.

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

4 authors at 2 institutions in 2 countries.

Asma HassaniDepartment of Microbiology and Immunology, College of Medicine and Health Sciences, Tawam Hospital Campus, United Arab Emirates University, Al Ain, UAE.
John R CorboyDepartment of Neurology, University of Colorado School of Medicine, Rocky Mountain MS Center at University of Colorado, Aurora, United States of America.
Suhail Al-SalamDepartment of Pathology, College of Medicine and Health Sciences, Tawam Hospital Campus, United Arab Emirates University, Al Ain, UAE.
Gulfaraz KhanDepartment of Microbiology and Immunology, College of Medicine and Health Sciences, Tawam Hospital Campus, United Arab Emirates University, Al Ain, UAE.ORCID 0000-0001-6836-1783
United Arab Emirates University · AERocky Mountain MS Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multiple sclerosis (MS) is a chronic neuroinflammatory condition of the central nervous system (CNS). It is a major cause of neurological disability in young adults, particularly women. What triggers the destruction of myelin sheaths covering nerve fibres is unknown. Both genetic and infectious agents have been implicated. Of the infectious agents, Epstein-Barr virus (EBV), a common herpesvirus, has the strongest epidemiological and serological evidence. However, the presence of EBV in the CNS and demonstration of the underlying mechanism(s) linking EBV to the pathogenesis of MS remain to be elucidated. We aimed at understanding the contribution of EBV infection in the pathology of MS. We examined 1055 specimens (440 DNA samples and 615 brain tissues) from 101 MS and 21 non-MS cases for the presence of EBV using PCR and EBER-in situ hybridization (EBER-ISH). EBV was detected by PCR and/or EBER-ISH in 91/101 (90%) of MS cases compared to only 5/21 (24%) of non-MS cases with other neuropathologies. None of the samples were PCR positive for other common herpesviruses (HSV-1, CMV, HHV-6). By quantitative PCR, EBV viral load in MS brain was mainly low to moderate in most cases. However, in 18/101 (18%) of MS cases, widespread but scattered presence of EBV infected cells was noted in the affected tissues by EBER-ISH. Immunohistochemical analysis of EBV gene expression in the 18 heavily infected cases, revealed that the EBV latent protein EBNA1, and to a lesser extent the early lytic protein BZLF1 were expressed. Furthermore, using double-staining we show for the first time that astrocytes and microglia, in addition to B-cells can also be infected. To the best of our knowledge, this is the most comprehensive study demonstrating that EBV is present and transcriptionally active in the brain of most cases of MS and supports a role for the virus in MS pathogenesis. Further studies are required to address the mechanism of EBV involvement in MS pathology.

Indexed as

B-LymphocytesBrainHerpesvirus 4, HumanHumansIn Situ HybridizationMultiple SclerosisReal-Time Polymerase Chain ReactionViral Load

Identifiers

PMID29394264
PMCPMC5796799
OpenAlexW2786871799

What OpenQuestion holds

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Registered trials

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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.