Is There a Connection Between the Epstein-Barr Virus and MS?

by Lisa Fields Health Writer

What causes multiple sclerosis (MS)? No one knows for sure. But for years researchers have trained a curious eye upon the Epstein-Barr virus (EBV). Multiple studies show some intriguing associations between MS and EBV. For instance, most people with MS test positive for EBV antibodies, leading some experts to believe that prior EBV infection may be a possible cause of MS—while others think that latent, lurking EBV can be triggered into reactivation by environmental risk factors that together lead to MS. Keep reading. We’ll share all we know.

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Wait, What’s the Epstein-Barr Virus, Again?

According to the Mayo Clinic, EBV is a common virus that’s also linked to mononucleosis (a.k.a. “the kissing disease,” which spreads through saliva and causes fatigue and sore throat, sometimes for weeks). EBV is so common that 90% to 95% of the population is infected with it, says Kassandra Munger, Sc.D., an MS researcher in the department of nutrition at the Harvard T.H. Chan School of Public Health in Boston. However, mononucleosis is not generally the result: “Most people experience the first EBV infection EBV as a child. Typically those infections are asymptomatic. You’re just infected–you don’t even know it.”

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EBV in Teens and Adults Tends to Be More Severe

Still, while EBV infection tends to be mild or even go unnoticed in children, it can cause a stronger reaction in teenagers and adults. If you’ve ever had mononucleosis, EBV was likely the culprit—it’s the most common cause. (Another virus, cytomegalovirus, causes a small percentage of mono cases, usually mild, and its connection to MS is unclear.) “When [older kids] go to college or join the military and are being exposed to new individuals, they may be infected with EBV,” Dr. Munger explains. “Some will be asymptomatic, some may have mild colds. About half of those infections will [lead to] mono.”

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Having EBV-Related Mono as a Young Adult Ups Your Risk for MS

Now, for the EBV-MS connection: According to Dr. Munger’s research, your risk of getting multiple sclerosis more than doubles if you’ve had mono caused by EBV as a young adult. “Individuals who’ve experienced infectious mono [which usually happens in the teen or adult years] have about a two-fold increased risk of developing MS. This has been shown in many different populations and many study designs and different criteria for exposure. It’s very consistent, and that also plays into the evidence for EBV being causally related to MS,” says Dr. Munger.

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There’s a Strong Connection Between EBV Antibodies and Early MS

New research has found even more intriguing associations between EBV and MS. A German study published in May 2020 revealed that among 901 patients of all ages in the earliest stages of MS, 100% had EBV antibodies. The patients whose blood was tested for antibodies in the study all had been diagnosed with either clinically isolated syndrome (CIS)—which is the first flareup of MS-like symptoms but is not yet considered an official MS diagnosis—or early relapsing-remitting multiple sclerosis (RRMS). The researchers concluded EBV plays a role in MS.

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Additional Research Links EBV Infection, Mono, and MS

Because most people become infected with EBV at a young age, it’s tricky to find people who haven’t been exposed to the virus—but Dr. Munger’s earlier research from 2010 identified people in the U.S. military who were EBV-negative. That study followed 38 EBV-negative people over time. Blood tests showed that 20 of the 38 eventually became infected with EBV. Interestingly, 10 of those who became EBV-positive later developed MS, while none of the people who remained EBV-negative did. “I think that study is our strongest study suggesting that EBV infection may be required for MS development,” Dr. Munger says.

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While Evidence Is Mounting, More Research Is Needed

While the German researchers wrote, “MS could be a rare, late complication of EBV infection,” other experts say no. “It can’t be a ‘late complication’ if some people never had the EB virus and still get MS. Other studies have not shown a 100-percent (infection rate),” says Barry Hendin, M.D., chief medical officer of the MS Association of America. And in Dr. Munger’s study, people developed MS three to five years after EBV infection, a short enough time frame not to be considered late, she says. “MS is likely a rare complication of Epstein-Barr virus infection. It’s not proven, it’s not accepted within the field—but it is getting a lot of attention.”

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Some Believe EBV Is Just One Risk Factor Among Many

Another idea getting attention is that multiple risk factors—including the presence of EBV—can occur simultaneously, creating the right mix to cause MS. Many experts “think of EBV as one of many potential triggers that makes a susceptible person more likely to actually develop MS, [such as] cigarette smoking, lack of vitamin D, and lack of sun exposure,” says Dr. Hendin. He adds, “[EBV is a] leading candidate in the viral trigger theory, but it’s not the exclusive, because there are other triggers as well.”

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Genetic Predisposition and EBV Together May Play a Role, Too

Experts believe that a genetic susceptibility may make someone more prone to getting MS—with a little help from EBV, though more research is needed on this. “We’ve got a number of genes, approximately 50-plus, which influence susceptibility to autoimmunity, including MS,” Dr. Hendin says. “If you’re high on the susceptibility genes and low in the protective genes, you’re more likely to get MS, given a certain trigger.” Dr. Munger agrees. “Maybe within that right mix of genes with the EBV infection ... there’s an interaction happening.”

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On the Horizon: An EBV Vaccine to Possibly Help Prevent MS

Researchers are working to create an EBV vaccine. If effective, it may be helpful for the next generation. “We would hope that it would reduce the incidence of a wide variety of things, including MS, but that remains to be proven,” Dr. Hendin says. The vaccine could be given during childhood, and may be effective even among those who are already EBV-positive before getting vaccinated, he adds. “The vaccines that are being looked at are less about preventing the primary [EBV] infection, but rather preventing the sequelae [long-term consequences] of the infection, preventing infectious mononucleosis—and possibly MS.”

Lisa Fields
Meet Our Writer
Lisa Fields

Lisa Fields is a full-time freelance health writer based in South Jersey who writes about chronic diseases, sleep problems and ways that stress and emotions can impact health. She writes frequently for WebMD and Reader’s Digest. She has also been published by The New York Times, Good Housekeeping, Women’s Health, Redbook and many other publications.