A connection between the human herpesvirus Epstein-Barr and multiple sclerosis (MS) has long been suspected but has been difficult to prove. Epstein-Barr virus (EBV) is the primary cause of mononucleosis and is so common that 95 percent of adults carry it. Unlike Epstein-Barr, MS, a devastating demyelinating disease of the central nervous system, is relatively rare. It affects 2.8 million people worldwide. But people who contract infectious mononucleosis are at slightly increased risk of developing MS. In the disease, inflammation damages the myelin sheath that insulates nerve cells, ultimately disrupting signals to and from the brain and causing a variety of symptoms, from numbness and pain to paralysis.
To prove that infection with Epstein-Barr causes MS, however, a research study would have to show that people would not develop the disease if they were not first infected with the virus. A randomized trial to test such a hypothesis by purposely infecting thousands of people would of course be unethical.
Instead researchers at the Harvard T. H. Chan School of Public Health and Harvard Medical School turned to what they call “an experiment of nature.” They used two decades of blood samples from more than 10 million young adults on active duty in the U.S. military (the samples were taken for routine HIV testing). About 5 percent of those individuals (several hundred thousand people) were negative for Epstein-Barr when they started military service, and 955 eventually developed MS. The researchers were able to compare the outcomes of those who were subsequently infected and those who were not. The results, published on September 13 in Science, show that the risk of multiple sclerosis increased 32-fold after infection with Epstein-Barr but not after infection with other viruses. “These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS,” the researchers wrote.