A Viral Cause of MS

Scientists have long suspected that there is connection between infections with Epstein Barr Virus (EBV), the agent responsible for infectious mononucleosis or the Kissing Disease and the development of Multiple Sclerosis or MS. The challenge has been finding proof of such a link. It's not like you can infect large numbers of people with EBV and see if they develop MS later in life, that would not be ethical. Fortunately, scientists already had a source of human samples to work with.

Researchers at the Harvard T. H. Chan School of Public Health and Harvard Medical School took advantage of twenty years of blood samples originally collected for HIV testing from 10 million young adults that went on active military service. Several hundred thousand of those people (about 5%) were not infected with EBV at the start of their military service and 955 of them later developed MS. Scientists were able to determine if those with or without EBV infections were more likely to develop MS. It turns out that an infection with EBV increases the risk of developing MS.

Most people in the world, especially in developing countries, are infected with EBV early in life with many exhibiting no or mild illness. In the US, when teens or adolescents become infected, they can develop infectious mononucleosis or the "mono" of high school infamy with symptoms that include extreme fatigue, fever, sore throat, and swollen lymph nodes which can last for two to four weeks. After infection, EBV becomes dormant, and people remain infected throughout their lives without any symptoms.

Scientists had three blood samples for each person who developed MS, one taken in their early twenties when they joined the military, one many years later before symptoms of MS appeared and one in between. The samples were tested for the appearance of EBV antibodies indicative of an infection. These samples were matched with two controls who were of the same age, sex, race or ethnicity, and branch of the military. Out of the 955 people who developed MS, they were able assemble complete samples from 801 of them and 1,566 controls, 35 of whom tested negative for EBV initially as well as 107 of the controls. Only one of those who developed MS did not show signs of EBV infection before the symptoms of MS appeared. This could be explained by that person's samples being taken before EBV infection or there are other less common triggers of MS. Despite this one outlier, the data is striking that EBV infection raises the risk of developing MS by 32-fold.

To make sure it was EBV, scientists also looked for antibodies to another Herpesvirus, cytomegalovirus in the samples and did not find any differences between people with MS and controls. Among the samples scientists scanned 30 MS and 30 controls for most of the viruses that infect humans and found no virus other than EBV correlated with MS. To make sure the MS arose after EBV infection and not before, scientists measured a protein marker for nerve cell damage that precedes the development of MS which rose after EBV infection and before clinical signs of MS.

The big question that remains is how does EBV infection lead to MS? Since most people are infected with EBV, there must be other factors that combine with EBV to trigger MS, but scientists are not sure what they are. Factors such as a genetic predisposition, or environmental factors such as Vitamin D deficiencies, and smoking are candidates. At least two EBV vaccines are in clinical trials that may reduce EBV infections as well as both short-term disease and long term consequences such as some cancers and MS.