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Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis
Abstract
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system of unknown etiology. We tested the hypothesis that MS is caused by Epstein-Barr virus (EBV) in a cohort comprising more than 10 million young adults on active duty in the US military, 955 of whom were diagnosed with MS during their period of service. Risk of MS increased 32-fold after infection with EBV but was not increased after infection with other viruses, including the similarly transmitted cytomegalovirus. Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion. These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.
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“This phenomenon is particularly relevant considering recent data demonstrating that EBV infection is a necessary risk factor for MS and that cross-reactive immune responses between EBV antigens and CNS proteins may contribute to disease initiation [211, 212].”
From Insights and challenges on animal models for progressive multiple sclerosis (2026) · cites this paper as [212]
In the citing paper
“For example, type 1 diabetes mellitus was linked to enterovirus infections185 and multiple sclerosis to Epstein–Barr virus (EBV) infections186.”
From COVID-19 and cellular senescence (2023) · cites this paper as [186]
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Shaping the host cell environment with viral noncoding RNAs
Gorbea, C. M., Elhakiem, A., & Cazalla, D. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.12.008 · Cited by 5
Immunologic prediction of long COVID
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DNA Fragility and Repair: Some Personal Recollections
Lindahl, T. R. (2023) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-071322-020214 · Cited by 5
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Genetic influences on disease course and severity, 30 years after a clinically isolated syndrome
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Is multiple sclerosis a glymphaticopathy?
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Milk and multiple sclerosis: A possible link?
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Voiding Phase Dysfunction in Multiple Sclerosis
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The effects of urolithin A on poly I:C-induced microglial activation
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“For instance, Bjornevik et al. recently found that Epstein-Bar virus (EBV) infection in humans increases the risk of multiple sclerosis (MS) by 32-fold, making EBV one of the most important triggers for the development of MS (Bjornevik et al., 2022).”
BackgroundMarazziti, D., Massa, L., Carbone, M. G., Palermo, S., Arone, A., D'Angelo, G., Crivelli, N. S. B., Gurrieri, R., Perrone, P., Palagini, L., et al. (2024) · PubMed Central · doi:10.36131/cnfioritieditore20240101 · Cited by 6
Genetic and early life factors influence on time-to-multiple sclerosis diagnosis: A UK Biobank study
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Molecular dissection of HERV-W dependent microglial- and astroglial cell polarization
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Epstein–Barr virus flare: A multiple sclerosis attack
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“[3,4,17,38] Although the literature masks B-cells’ neuroinvasion and its link to EBV, it remains not fully understood how the issue affects the stage and course of MS and a thorough examination is needed.”
BackgroundViral insulin/IGF-like peptides inhibit IGF-1 receptor signaling to enhance viral replication
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Comprehensively identifying Long Covid articles with human-in-the-loop machine learning
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EBV linked to multiple sclerosis
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Molecular mechanisms associated with multiple sclerosis progression, severity and phenotypePreprint
Kosa, P. F., Lumbard, K., Wang, J., Liang, C., Masvekar, R., Kim, Y., Varosanec, M., Jennings, L. L., & Bielekova, B. (2022) · medRxiv · doi:10.1101/2022.10.14.22281095 · Cited by 5
Herpes viral infection and the multiple sclerosis prodrome: is HHV-6A infection a second hit?
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Systems Analysis of Immune Changes after B-cell Depletion in Autoimmune Multiple SclerosisPreprint
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“…of effector Treg frequency both by transcriptomic and protein expression, it will be of interest to more precisely identify whether there are differences in specific myelin antigens and other antigens, as recent studies indicate EBV infection of B cells is associated with the onset of MS 56 .”
BackgroundWhat would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease?
Brutkiewicz, R. R., Cao, W., Morgan, D., Reis, R. S. D., Suryadevara, V., Willette, A. A., Willette, S. A., Wyatt-Johnson, S. K., & Duggan, M. R. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2025.05.009 · Cited by 3
Metadata
- Authors
- Bjornevik, K., Cortese, M., Healy, B. C., Kuhle, J., Mina, M. J., Leng, Y., Elledge, S. J., Niebuhr, D. W., Scher, A. I., Munger, K. L., & Ascherio, A.
- Affiliations
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
- Uniformed Services University of the Health Sciences (US)
- Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
- Corresponding author
- Cortese, Marianna
- Munger, Kassandra L.
- Ascherio, Alberto
- ORCID
- Venue
- Science
- Published
- 2022-01-21
- Volume
- 375
- Issue
- 6578
- Pages
- 296-301
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4205972999
- Cited by
- 2,049
- References
- 51
- Citations by year
- 2026: 354 · 2025: 412 · 2024: 461 · 2023: 432 · 2022: 388
- FWCI
- 289.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke (R01NS042194, R01NS046635, R01NS103891)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- multiple sclerosis, Epstein-Barr virus, viral etiology, neurofilament light chain, neuroaxonal degeneration, cytomegalovirus, demyelinating disease, military personnel
- MeSH terms
- Antibodies, Viral, Cytomegalovirus, Herpesvirus 4, Human, Female, Humans, Longitudinal Studies, Male, Military Personnel, Multiple Sclerosis, Risk Factors, Cohort Studies, Biomarkers, Prevalence, Neurofilament Proteins, Age of Onset, Epstein-Barr Virus Infections, Young Adult
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