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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]
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“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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“The role of infection as the temporally initiating event in MS etiology is the focus of current work 15,58 https://doi.org/10.1038/s41591-024-02938-3 crucial to the differentiation of causal versus spuriously associated features of the MS prodrome.”
BackgroundInfluentialLong-Term Outcomes of Pediatric Infections: From Traditional Infectious Diseases to Long Covid
Buonsenso, D., Gennaro, L. D., Rose, C. D., Morello, R., D’Ilario, F., Zampino, G., Piazza, M., Boner, A. L., Iraci, C., O’Connell, S., et al. (2022) · Future Microbiology · doi:10.2217/fmb-2022-0031 · Cited by 97
Inflammation at the crossroads of COVID-19, cognitive deficits and depression
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From the prodromal stage of multiple sclerosis to disease prevention
Marrie, R. A., Allegretta, M., Barcellos, L. F., Bebo, B. F., Calabresi, P. A., Correale, J. D., Davis, B. G., Jager, P. L. D., Gasperi, C., Greenbaum, C. J., et al. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00686-x · Cited by 91
Self-citationBroader Epstein–Barr virus–specific T cell receptor repertoire in patients with multiple sclerosis
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Microbiome epidemiology and association studies in human health
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EBV induces CNS homing of B cells attracting inflammatory T cells
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Urgency and necessity of Epstein-Barr virus prophylactic vaccines
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Open problems in human trait genetics
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Toward Precision Phenotyping of Multiple Sclerosis
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Chronic effects of inflammation on tauopathies
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How EBV Infects: The Tropism and Underlying Molecular Mechanism for Viral Infection
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Cell-free DNA-based liquid biopsies in neurology
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A gB nanoparticle vaccine elicits a protective neutralizing antibody response against EBV
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Blood–Brain Barrier Disruption in Neuroimmunological Disease
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“The risk of MS was 32-fold higher following EBV infection, and the serum concentration of the neurofilament light chain was increased after EBV seroconversion in MS [61].”
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Molecular mimicry as a mechanism of viral immune evasion and autoimmunity
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“In addition, we observe that for one of the most common herpesviruses (EBV), mimicry is signi fi cantly higher in latently expressed proteins compared to lytic proteins, further suggesting evasion of the adaptive immune system may be more advantageous duringthelatent stage of infection.”
InfluentialThe age at onset of relapsing-remitting multiple sclerosis has increased over the last five decades
Romero-Pinel, L., Bau, L., Matas, E., León, I., Muñoz‐Vendrell, A., Arroyo, P., Aumatell, C. M., Martínez-Yélamos, A., & Martínez‐Yélamos, S. (2022) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2022.104103 · Cited by 83
Methionine metabolism controls the B cell EBV epigenome and viral latency
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The Role of BDNF in Multiple Sclerosis Neuroinflammation
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Sequential immunotherapy: towards cures for autoimmunity
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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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