Cited by 2,049Multiple Sclerosis Research StudiesViral-associated cancers and disordersCytomegalovirus and herpesvirus research

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Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis

Bjornevik, Kjetil, Cortese, Marianna, Healy, Brian C., Kuhle, Jens, Mina, Michael J., Leng, Yumei, Elledge, Stephen J., Niebuhr, David W., Scher, Ann I., Munger, Kassandra L., Ascherio, Alberto·2022·Science

DOI 10.1126/science.abj8222

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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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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
The International Multiple Sclerosis Genetics Consortium & The Wellcome Trust Case Control Consortium 2 (2011) · Nature · doi:10.1038/nature10251 · Cited by 2,697
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Reich, D. S., Lucchinetti, C. F., & Calabresi, P. A. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1401483 · Cited by 2,491
The Immune Epitope Database (IEDB): 2018 update
Vita, R., Mahajan, S., Overton, J. A., Dhanda, S. K., Martini, S. R., Cantrell, J. R., Wheeler, D. K., Sette, A., & Peters, B. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky1006 · Cited by 2,194
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Neurofilaments as biomarkers in neurological disorders
Khalil, M., Teunissen, C. E., Otto, M., Piehl, F., Sormani, M. P., Gattringer, T., Barro, C., Kappos, L., Comabella, M., Fazekas, F., et al. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0058-z · Cited by 1,988
Negative Controls: A Tool for Detecting Confounding and Bias in Observational Studies
Lipsitch, M., Tchetgen Tchetgen, E., & Cohen, T. (2010) · Epidemiology · doi:10.1097/ede.0b013e3181d61eeb · Cited by 1,583
Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis
Olsson, T. P., Barcellos, L. F., & Alfredsson, L. S. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.187 · Cited by 1,263
Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis
Disanto, G., Barro, C., Benkert, P., Naegelin, Y., Schädelin, S., Giardiello, A., Zecca, C., Blennow, K., Zetterberg, H., Leppert, D., et al. (2017) · Annals of Neurology · doi:10.1002/ana.24954 · Cited by 1,164
Epstein-Barr virus: exploiting the immune system
Thorley‐Lawson, D. A. (2001) · Nature reviews. Immunology · doi:10.1038/35095584 · Cited by 942

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Tudorancea, I. M., Ciorpac, M., Stanciu, G. D., Caratașu, C.-C., Săcărescu, A., Ignat, B. E., Burlui, A., Rezuş, E., Creangă-Murariu, I., Alexa‐Stratulat, T., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10102492 · Cited by 28
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Thomas, O. G., Haigh, T. A., Croom-Carter, D. S. G., Leese, A. M., van Wijck, Y., Douglas, M. R., Rickinson, A. B., Brooks, J. M., & Taylor, G. S. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1012177 · Cited by 25
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“Similarly, epitope indistin-guishability between EBNA1, encoded by Epstein–Barr virus (EBV), and host GlialCAM likely contributes to the autoreactive lymphocyte expansion seen in multiple sclerosis (MS) 2,3 .”
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“Furthermore, a longitudinal study conducted on 10 million young adults observed a 32-fold increased risk of developing MS following EBV infection [91].”
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Background
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The case for targeting latent and lytic Epstein-Barr virus infection in multiple sclerosis
Giovannoni, G., James, L. K., Adeniran, A. A., Gold, J., Young, L. S., Selwood, D. L., Baker, D., & Dobson, R. (2025) · Brain · doi:10.1093/brain/awaf170 · Cited by 23
“4 However, despite strong epidemiological evidence linking EBV to MS development, a mechanistic understanding of how EBV might cause MS is lacking.”
A probiotic approach identifies a Treg-centred immunoregulation via modulation of gut microbiota metabolites in people with multiple sclerosis and healthy individuals
Träger, C., Kaiser, M., Freudenstein, D., Heckscher, S., Dettmer, K., Oefner, P. J., Liebisch, G., Hiergeist, A., Gessner, A., Lee, D.-H., et al. (2025) · EBioMedicine · doi:10.1016/j.ebiom.2025.105743 · Cited by 21
Early multiple sclerosis activity associated with TBX21+CD21loCXCR3+ B cell expansion resembling EBV-induced phenotypes
SoRelle, E. D., Haukenfrers, E., Horn, G. Q., Jain, V., Giarraputo, J., Abramson, K., Hocke, E., Cooney, L. A., Harris, K. M., Zamvil, S. S., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.188543 · Cited by 21
“MS is a chronic neuroinflammatory disease with a 3:1 female bias (23) in which both pathogenic ABCs (49, 50) and epidemiologic evidence of EBV etiology in disease onset (a 32-fold risk from EBV seropositivity after childhood) have been identified (51, 52).”
Myelin injury precedes axonal injury and symptomatic onset in multiple sclerosis
Abdelhak, A., Cerono, G., Sheikhzadeh, F., Harroud, A., Ning, K., Zamecnik, C. R., Sowa, G. M., Boscardin, W. J., Cordano, C., Tubati, A., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-04014-w · Cited by 27
“Studying samples from the presymptomatic stage of MS enables valuable insights into MS pathophysiology, timing and the magnitude of central nervous sys-tem (CNS) injury 2,3 .”
Genome-wide analysis of schizophrenia and multiple sclerosis identifies shared genomic loci with mixed direction of effects
Ahangari, M. M., Everest, E., Nguyen, T.-H., Verrelli, B. C., Webb, B. T., Bacanu, S., Turanlı, E. T., & Riley, B. P. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.06.007 · Cited by 21
Revisiting IgG Antibody Reactivity to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Its Potential Application to Disease Diagnosis
Sepúlveda, N., Malato, J., Sotzny, F., Grabowska, A. D., Fonseca, A., Cordeiro, C., Graça, L., Biecek, P., Behrends, U., Mautner, J., et al. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.921101 · Cited by 21
MINI-review of Epstein-Barr virus involvement in multiple sclerosis etiology and pathogenesis
Aloisi, F., & Cross, A. H. (2022) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2022.577935 · Cited by 21
The gut microbiome molecular mimicry piece in the multiple sclerosis puzzle
Elsayed, N. S., Aston, P., Bayanagari, V. R., & Shukla, S. K. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.972160 · Cited by 22
How does age determine the development of human immune-mediated arthritis?
Degboé, Y., Vastert, S. J., Prakken, B. J., & McInnes, I. B. (2022) · Nature Reviews Rheumatology · doi:10.1038/s41584-022-00814-3 · Cited by 21
Molecular disease mechanisms of human antineuronal monoclonal autoantibodies
Duong, S. L.-L., & Prüß, H. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2022.09.011 · Cited by 23
Sequence similarity between SARS-CoV-2 nucleocapsid and multiple sclerosis-associated proteins provides insight into viral neuropathogenesis following infection
Lake, C. M., & Breen, J. J. (2023) · Scientific Reports · doi:10.1038/s41598-022-27348-8 · Cited by 21
Delivery Route Considerations for Designing Antigen‐Specific Biomaterial Strategies to Combat Autoimmunity
Ackun‐Farmmer, M. A., & Jewell, C. M. (2023) · Advanced NanoBiomed Research · doi:10.1002/anbr.202200135 · Cited by 21
Graph-Based Analysis of Brain Connectivity in Multiple Sclerosis Using Functional MRI: A Systematic Review
Hejazi, S., Karwowski, W., Farahani, F. V., Marek, T., & Hancock, P. A. (2023) · Brain Sciences · doi:10.3390/brainsci13020246 · Cited by 23
Roadmap for understanding mechanisms on how Epstein–Barr virus triggers multiple sclerosis and for translating these discoveries in clinical trials
Lanz, T. V., Robinson, W. H., Ho, P. P.-K., & Steinman, L. (2023) · Clinical & Translational Immunology · doi:10.1002/cti2.1438 · Cited by 22
The hide-and-seek game of the oncogenic Epstein-Barr virus-encoded EBNA1 protein with the immune system: An RNA G-quadruplex tale
Dinh, V.-T., Loaëc, N., Quillévéré, A., Sénéchal, R. L., Keruzoré, M., Martins, R. P., Granzhan, A., & Blondel, M. (2023) · Biochimie · doi:10.1016/j.biochi.2023.07.010 · Cited by 21
The Probable Infectious Origin of Multiple Sclerosis
Landry, R. L., & Embers, M. E. (2023) · NeuroSci · doi:10.3390/neurosci4030019 · Cited by 21
The elusive nature of the oligoclonal bands in multiple sclerosis
Kennedy, P. G. E., George, W., & Yu, X. (2023) · Journal of Neurology · doi:10.1007/s00415-023-12081-7 · Cited by 24
The Impact of Microbiota–Immunity–Hormone Interactions on Autoimmune Diseases and Infection
Martinelli, S., Nannini, G., Cianchi, F., Coratti, F., & Amedei, A. (2024) · Biomedicines · doi:10.3390/biomedicines12030616 · Cited by 22
“These findings provide a mechanistic link between EBV infection and the pathobiology of MS [117,118].”
Shared and distinct interactions of type 1 and type 2 Epstein-Barr Nuclear Antigen 2 with the human genome
Viel, K. C. M. F., Parameswaran, S., Donmez, O. A., Forney, C. R., Hass, M. R., Yin, C., Jones, S. H., Prosser, H. K., Diouf, A. A., Gittens, O. E., et al. (2024) · BMC Genomics · doi:10.1186/s12864-024-10183-8 · Cited by 21
“For example, a recent study reported a 32-fold increase in MS risk following EBV infection and showed that MS flare ups occurred after an increase of EBV protein levels in the serum [10].”
The nucleic acid binding protein SFPQ represses EBV lytic reactivation by promoting histone H1 expression
Murray‐Nerger, L. A., Lozano, C., Burton, E. M., Liao, Y., Ungerleider, N., Guo, R., & Gewurz, B. E. (2024) · Nature Communications · doi:10.1038/s41467-024-48333-x · Cited by 21
Peroxisomal very long-chain fatty acid transport is targeted by herpesviruses and the antiviral host response
Weinhofer, I., Buda, A., Kunze, M., Palfi, Z., Traunfellner, M., Hesse, S., Villoria-Gonzalez, A., Hofmann, J., Hametner, S., Regelsberger, G., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03867-y · Cited by 20
Multiple sclerosis: Motor dysfunction
Younger, D. S. (2023) · Handbook of clinical neurology · doi:10.1016/b978-0-323-98817-9.00016-8 · Cited by 26
Risk of multiple sclerosis in individuals with infectious mononucleosis: a national population-based cohort study using hospital records in England, 2003–2023
Goldacre, R. (2024) · Multiple Sclerosis Journal · doi:10.1177/13524585241237707 · Cited by 20
“3,4,17 Instead, these findings lend weight to the existing body of literature on the association between IM (the clinical disease manifestation of EBV) and MS. 12,18,19 The comparison here is between individuals hospitalised with IM and the general population (represented by the reference cohort).”
Background
MiRNA-based therapeutic potential in multiple sclerosis
Zabalza, A., Pappolla, A., Comabella, M., Montalbán, X., & Malhotra, S. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1441733 · Cited by 23
Epstein-Barr Virus Exposure Precedes Crohn's Disease Development
Nandy, A., Petralia, F., Porter, C., Elledge, S. J., Anand, R., Croitoru, K., Dunn, G., Dennis-Heyward, E. A., Eran, A., Field, M., et al. (2025) · Gastroenterology · doi:10.1053/j.gastro.2025.01.247 · Cited by 20
Self-citation
Advancements in multiple sclerosis
Montague, T., Drummond, J., Ng, K., & Parratt, J. (2025) · Internal Medicine Journal · doi:10.1111/imj.70023 · Cited by 21
“20 Moreover, serum neuro ﬁ lament, a biomarker of neuroaxonal injury, increased after EBV seroconversion.”
Influential
Human Immune Responses to Epstein-Barr Virus Highlighted by Immunodeficiencies
Latour, S. (2025) · Annual Review of Immunology · doi:10.1146/annurev-immunol-082323-035455 · Cited by 19
Epstein-Barr Virus Load Correlates with Multiple Sclerosis-Associated Retrovirus Envelope Expression
Pérez‐Pérez, S., Domínguez‐Mozo, M. I., García‐Martínez, M. Á., Ballester-González, R., Nieto-Gañán, I., Arroyo, R., & Álvarez‐Lafuente, R. (2022) · Biomedicines · doi:10.3390/biomedicines10020387 · Cited by 20

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: Bjornevik, Kjetil
Cortese, Marianna
Healy, Brian C.
Mina, Michael J.
Leng, Yumei
Elledge, Stephen J.
Munger, Kassandra L.
Ascherio, Alberto
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2022-01-21
Volume: 375
Issue: 6578
Pages: 296-301
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.abj8222
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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Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis

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