Epstein-Barr virus (EBV) is an incredibly prevalent virus that infects over 90% of people globally. It is most commonly known for causing infectious mononucleosis, also called “mono”.[1] Research has found mounting evidence of a connection between EBV and MS, most notably some that suggests EBV may be an important trigger for MS onset. A 20-year epidemiological study of over 10 million U.S. military personnel found that EBV infection was associated with a 32-fold increased risk of developing MS.[2] Using multiple blood samples drawn both before disease onset and afterward, the researchers found that early markers of MS disease activity consistently began after EBV exposure, but not before. Out of the entire cohort, 955 people were diagnosed with MS and only 1 person did not demonstrate a history of EBV infection (indicated by a lack of EBV-specific antibodies in the blood). This is in line with previous research finding that over 99% of people with MS had EBV-specific antibodies.[3]
Further supporting the link between EBV and MS is the finding of several cross-reactive antibodies that attack both EBV proteins — most notably EBV nuclear antigens (EBNA) — and central nervous system proteins involved in MS.[1][4][5] This is a phenomenon called molecular mimicry, which is when a molecule from a foreign invader (in this case, EBV) looks very similar to a molecule in the human body and therefore antibodies generated against the virus may also inappropriately attack human tissues. These EBNA-specific antibodies have been found to be elevated in people with MS compared to people without the disease and are associated with an increased risk of MS development.[6]
So, why is MS so uncommon when EBV is so prevalent? This likely depends heavily on genetics, particularly variations in the gene HLA-DRB1.[1] This gene controls how viral proteins are presented to the immune system upon infection, which may promote the generation of cross-reactive antibodies, meaning that many people who are infected with EBV won’t necessarily generate them. There is also evidence that other genetic variants that affect how the immune system responds to EBV may play a role.[7]