Although genetics risk explains the familial clustering of multiple sclerosis (MS), it cannot fully explain the geographic distribution of MS and the changes in risk that occur with migration. Infections have been suggested as a possible explanation. While many agents have been tested, the most convincing candidate for involvement in MS is Epstein-Barr virus (EBV).
EBV is present in all populations and infects over 90% of individuals within the first decades of life. EBV infection results in a life-long persistence of the virus in the host’s B-lymphocytes. EBV infection has been associated with numerous cancers, including Burkitt lymphoma, Hodgkin lymphoma, and nasopharyngeal carcinoma.
Primary EBV infection is usually at an early age and is typically asymptomatic. However, primary infection during adolescence or adulthood often manifests as infectious mononucleosis, which has been associated with a more than 2-fold increased risk of MS.1
Mononucleosis, like MS, is rare in conditions of poor hygiene (ie, in developing countries), where virtually all children are infected with EBV in the first years of life.
Perhaps most importantly, MS risk is extremely low in individuals who are EBV-negative. However, risk increases sharply following EBV infection, as shown in a recent longitudinal study.2
The biological mechanism by which EBV may cause MS is not yet known. It remains to be determined whether EBV influences the disease course of MS.
1. Handel AE, Williamson AJ, Disanto G, et al. An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis. PLoS One. 2010;5(9). pii: e12496.
2. Levin LI, Munger KL, O’Reilly EJ, et al. Primary infection with the Epstein-Barr virus and risk of multiple sclerosis. Ann Neurol. 2010;67:824-830.