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

Kjetil Bjornevik^#¹, Marianna Cortese^#¹, Brian C Healy^{2

3

4}, Jens Kuhle⁵, Michael J Mina^{6

7

8}, Yumei Leng⁶, Stephen J Elledge⁶, David W Niebuhr⁹, Ann I Scher⁹, Kassandra L Munger^#¹, Alberto Ascherio^#^{1

10

11}

Affiliations

¹ Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
² Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, MA, USA.
³ Department of Neurology, Harvard Medical School, Boston, MA, USA.
⁴ Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA.
⁵ Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
⁶ Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Department of Genetics, and Program in Virology, Harvard Medical School, Boston, MA, USA.
⁷ Center for Communicable Disease Dynamics, Department of Epidemiology, and Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
⁸ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
¹⁰ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
¹¹ Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.

^# Contributed equally.

PMID: 35025605
DOI: 10.1126/science.abj8222

Free article

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

Kjetil Bjornevik et al. Science. 2022.

Free article

. 2022 Jan 21;375(6578):296-301.

doi: 10.1126/science.abj8222. Epub 2022 Jan 13.

Authors

Affiliations

¹ Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
² Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, MA, USA.
³ Department of Neurology, Harvard Medical School, Boston, MA, USA.
⁴ Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA.
⁵ Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
⁶ Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Department of Genetics, and Program in Virology, Harvard Medical School, Boston, MA, USA.
⁷ Center for Communicable Disease Dynamics, Department of Epidemiology, and Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
⁸ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
¹⁰ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
¹¹ Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.

^# Contributed equally.

PMID: 35025605
DOI: 10.1126/science.abj8222

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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Comment in

Epstein-Barr virus and multiple sclerosis.
Robinson WH, Steinman L. Robinson WH, et al. Science. 2022 Jan 21;375(6578):264-265. doi: 10.1126/science.abm7930. Epub 2022 Jan 13. Science. 2022. PMID: 35025606
EBV linked to multiple sclerosis.
Du Toit A. Du Toit A. Nat Rev Microbiol. 2022 Apr;20(4):189. doi: 10.1038/s41579-022-00701-4. Nat Rev Microbiol. 2022. PMID: 35110729 No abstract available.
Linking Epstein-Barr virus infection to multiple sclerosis.
Bordon Y. Bordon Y. Nat Rev Immunol. 2022 Mar;22(3):143. doi: 10.1038/s41577-022-00686-4. Nat Rev Immunol. 2022. PMID: 35140366 No abstract available.
New Evidence for Epstein-Barr Virus Infection as a Cause of Multiple Sclerosis.
Hacohen Y, Ciccarelli O. Hacohen Y, et al. Neurology. 2022 Apr 12;98(15):605-606. doi: 10.1212/WNL.0000000000200243. Epub 2022 Feb 10. Neurology. 2022. PMID: 35145009 No abstract available.
Epstein-Barr virus as a driver of multiple sclerosis.
Sollid LM. Sollid LM. Sci Immunol. 2022 Apr;7(70):eabo7799. doi: 10.1126/sciimmunol.abo7799. Epub 2022 Apr 1. Sci Immunol. 2022. PMID: 35363541
Guilty by association: Epstein-Barr virus in multiple sclerosis.
Bar-Or A, Banwell B, Berger JR, Lieberman PM. Bar-Or A, et al. Nat Med. 2022 May;28(5):904-906. doi: 10.1038/s41591-022-01823-1. Nat Med. 2022. PMID: 35538259 No abstract available.
A role for the Epstein-Barr virus in multiple sclerosis aetiology?
Hrastelj J, Robertson NP. Hrastelj J, et al. J Neurol. 2022 Jul;269(7):3962-3963. doi: 10.1007/s00415-022-11177-w. Epub 2022 May 31. J Neurol. 2022. PMID: 35639199 Free PMC article. No abstract available.
Epstein-Barr virus infection: the leading cause of multiple sclerosis.
He R, Du Y, Wang C. He R, et al. Signal Transduct Target Ther. 2022 Jul 16;7(1):239. doi: 10.1038/s41392-022-01100-0. Signal Transduct Target Ther. 2022. PMID: 35842414 Free PMC article. No abstract available.
Falling down the biological rabbit hole: Epstein-Barr virus, biography, and multiple sclerosis.
Horwitz RI, Hayes-Conroy A, Singer BH, Cullen MR, Badal K, Sim I. Horwitz RI, et al. J Clin Invest. 2022 Sep 1;132(17):e164141. doi: 10.1172/JCI164141. J Clin Invest. 2022. PMID: 36047497 Free PMC article. No abstract available.
Cancer research needs better databases.
Eisinger-Mathason TSK. Eisinger-Mathason TSK. Nature. 2022 Oct;610(7933):607. doi: 10.1038/d41586-022-03390-4. Nature. 2022. PMID: 36284188 No abstract available.
The biological rabbit hole: Only for the blind.
Hawkes CH, Giovannoni G, Lechner-Scott J, Levy M, Yeh A. Hawkes CH, et al. Mult Scler Relat Disord. 2022 Nov;67:104256. doi: 10.1016/j.msard.2022.104256. Epub 2022 Oct 18. Mult Scler Relat Disord. 2022. PMID: 36302291 No abstract available.

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

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

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