Published: 16 July 2022

DOI https://doi.org/10.1038/s41392-022-01100-0

Ruirui He, Yanyun Du & Chenhui Wang

In a recent study published in Science, Bjornevik and colleagues demonstrated Epstein-Barr virus (EBV) infection is a trigger for multiple sclerosis (MS) in a longitudinal analysis of more than 10 million US military individuals who were on active duty.1

MS is an autoimmune disease that originates in the central nervous system characterized by inflammatory demyelinating lesions. There is no consensus on the etiology of MS. However, we all know that MS is a multifactorial disease which can be influenced by genetic and environmental factors. Genetic factors associated with MS risk are mainly major histocompatibility class II (MHC II) alleles (e.g., HLA-DRB1*15:01, the earliest identified and most dominant risk factor in MS) and MHC I alleles (e.g., HLA-A*02 and HLA B*44, decreasing MS susceptibility). Additionally, more than 200 genetic loci have been identified to be associated with the risk of MS,2 but only a few specific genes or biological mechanisms of the identified genetic loci have been studied. Specific environmental exposures including ultraviolet radiation/vitamin D deficiency, cigarette smoking, diet, and viral infections have influence on the incidence of MS. Viral infection is one of the crucial environmental factors and most researches have focused on EBV, a highly B cell-tropic human herpesvirus, which infects about 95% of individuals worldwide. Significantly elevated risk of MS after EBV infection compared with EBV seronegative individuals supports a link between EBV infection and MS.3 In addition, anti-EBNAs antibody elevated in blood of MS patients, which can be detected years before MS onset.4 Although the hypothesis that EBV causes MS has been studied for many years, clear causality remains inconclusive.

In this study, Bjornevik et al. gave direct evidence that EBV infection is a critical contributor of MS based on a large cohort of more than 10 million young adults in the US military. Among this large population, 955 individuals of them were diagnosed with MS during their active-duty. In a 20-year collaboration with US military between 1993 and 2013, the authors collected up to three serum samples for each MS case before the date of disease onset (Fig. 1).

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https://www.nature.com/articles/s41392-022-01100-0#citeas