New research published in Science and Nature suggests that Epstein-Barr virus (EBV)—an infection contracted by more than 90% of adults—may be the "leading cause" of multiple sclerosis (MS), Kim Tingley reports for the New York Times Magazine.

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'Most people never know they're infected' with EBV

Typically, people contract EBV during their childhood, and it spreads through body fluids, most often saliva. When young children are infected, they usually develop symptoms that closely mirror a cold or the flu—if they even show symptoms at all.

When the infection occurs after puberty, it often results in infectious mononucleosis, a disease characterized by extreme fatigue, sore throat, fever, and swollen lymph nodes in the neck—symptoms that can last for weeks and even recur for years in chronic cases, Tingley writes.

EBV enters cells at the back of the throat and then invades B cells, a type of white blood cell that produces antibodies. Then, the virus replicates in some B cells, making proteins that can be recognized and subdued by the immune system. However, it can remain dormant in other cells.

"It's very stealthy," said Jeffrey Cohen, the chief of the Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases. "Most people never know they're infected."

"The vast majority of people who are infected are passing it around," Cohen added. "It's shed in our saliva the rest of our lives."

As a result, more than 90% of adults have EBV.

New research suggests EBV may be the "leading cause" of MS

"Scientists have long hypothesized that viruses, including [EBV], are involved in the development of autoimmune diseases, in which the immune system mistakenly attacks healthy tissue," Tingley writes.

In fact, "[p]eople have been trying for many, many decades to prove that a virus causes M.S. or rheumatoid arthritis," said William Robinson, the chief of the immunology and rheumatology division at Stanford University. "And they have not been able to convincingly demonstrate that it does."

To isolate EBV as a causal factor of MS, a study would need to find a group of people who do not have the virus—which would be challenging since only about 10% of the population doesn't have the virus by their mid-20s—and follow them over decades to see who becomes infected, and, of those, how many develop MS compared with how many without EBV develop MS.

However, in January, researchers from the Harvard T.H. Chan School of Public Health and elsewhere developed a novel method to determine whether EBV is a causal factor in MS.

For the study, they analyzed blood serum samples of U.S. military recruits archived in the Department of Defense serum repository. From 1993 to 2013, they identified cases of MS among active-duty U.S. military personnel. Then, they tested each subject's initial serum sample, their last sample before MS onset, and one sample taken in between. Among those tested, researchers found that of the 801 soldiers with MS, 800 of them also tested positive for EBV.

"In practical terms, if you're not infected with [EBV], your risk of [MS] is virtually zero," said Alberto Ascherio, a professor of epidemiology and nutrition at Harvard and a senior author of the Science study. "After infection, your risk jumps by over 30-fold," he added.

"The odds of that increase having occurred by chance are less than one in a million," Tingley writes.

One week after the Science study came out, Robinson and his colleagues published a separate paper in Nature showing how EBV triggers MS in some people.

According to the research, EBV produces proteins that mimic a protein in the myelin sheath, which is like "the insulation around your neurons," according to Robinson. When the immune system creates antibodies that attack the virus, they also attack the myelin. "Like electrical wires, if the insulation gets stripped off, it short-circuits," he added. "That's what results in [MS]." However, the "protein mix-up" can only account for around 25% of MS cases, Tingley writes.

Although the Science paper concludes that EBV is the "leading cause" of MS, Cohen noted that he wants to be cautious with the word "cause." While he believes the study proves that EBV is a necessary precondition for MS, he also noted that because so many people have EBV and so few of them develop MS, other factors likely play an important role in its development.

Notably, Tingley writes that the discovery of EBV as a precondition for MS "raises the prospect that a vaccine could prevent that disease—as well as other serious conditions—even if we never understand precisely why the virus behaves as it does in a given individual."

Previously, the link between EBV and MS had been viewed as controversial and commercial, popular interest in a vaccine had been "lukewarm," according to Hank Balfour, a professor of laboratory medicine, pathology and pediatrics at the University of Minnesota Medical School and the principal investigator of the Mono Project. "Now I think things will change," Balfour said.  (Tingley, New York Times Magazine, 2/23)