Epstein-Barr Virus and MS: What’s the Link?

Medically Reviewed by Christopher Melinosky, MD on June 03, 2024
5 min read

Multiple sclerosis (MS) is a chronic, inflammatory disease that affects your central nervous system. That includes your brain and spinal cord. When you have MS, your immune system attacks the protective layer around your nerve cells. Sometimes those cells die.

MS doesn’t have a cure, but scientists are one step closer to figuring out what triggers it. Strong evidence shows that viruses can trigger the process, especially Epstein-Barr virus (EBV). This research may guide scientists toward new and better ways to treat or prevent MS.

EBV is a type of herpes virus usually spread through saliva. Most people are infected with it sometime in childhood, when it may cause few to no symptoms. But EBV is the leading cause of infectious mononucleosis, aka mono. Mono usually shows up in adolescents and young adults.

Symptoms of EBV infection include:

  • Tiredness
  • Fever
  • Sore throat
  • Swollen lymph nodes in your neck
  • Body aches
  • Rash

You can spread EBV for only a matter of weeks. But like other herpes viruses, an inactive version will stick around in your body. This “latent” virus may become active again later on. You may or may not have any symptoms if that happens.

There isn’t a vaccine or cure for EBV.

Scientists have long suspected that EBV infection plays a big part in developing MS. A causal connection has been hard to prove. But new research offers strong evidence the two are linked. This scientific data comes from two new studies, including:

The Harvard study. To test the EBV theory, a research team led by scientists from the Harvard T.H. Chan School of Public Health looked at data from more than 10 million young adults on active duty in the U.S. military. Of that group, 955 were diagnosed with MS during their 20-year period of service.

On average, MS symptoms started about 10 years after the first blood sample.

Researchers knew the EBV infection status of 801 people who developed MS. They figured that out by testing blood samples taken every other year after the start of each person’s military service.

Results from the study show:

  • MS symptoms started about 5 years after the first EBV-positive results.
  • The odds of developing MS went up 32-fold after infection with EBV.
  • Other viruses didn’t raise the chances of MS.
  • Only one person who developed MS remained EBV-negative.

The team also looked at changes in the neurofilament light chain (NF-L). That’s a protein that helps support your nerve fibers or axons. NF-L ends up in the fluid around your brain and spinal cord when a disease like MS damages and breaks down the outer layer of your nerves.

NF-L is a common sign, or biomarker, for diseases that weaken or destroy nerve tissue. And for those who developed MS, researchers found that NF-L levels went up only after EBV infection.

The study didn’t look at whether EBV causes active disease or flare-ups in people who already have MS. It measured or compared samples of NF-L before, during, and after a diagnosis of MS. The study did measure disease activity.

The Stanford Medicine study. This team found evidence for something called molecular mimicry. That’s when the immune system targets germs and healthy cells because it can’t tell the difference between the two. This is commonly used to explain, at least partly, how viruses might cause MS.

The Stanford study found that 20 percent to 25 percent of people with MS make antibodies that stick to both a protein EBV makes and a protein the brain and spinal cord make.

Here’s how this molecular mix-up might trigger MS:

When you’re infected with EBV, certain white blood cells start fighting against EBNA1, or EBV nuclear antigen 1. But to the body, this virus protein can look a lot like one in your central nervous system called glial cell adhesion molecule, or GlialCAM.

GlialCAM is a key protein inside your myelin or the protective cover around nerve cells.

Researchers found that for some people with MS, antibodies to EBNA1 are “cross-reactive” with GlialCAM. As a result, the immune system can destroy both EBV proteins and an important part of healthy nerve cells.

The Harvard study stopped short of saying their results directly prove EBV triggers MS. But they suggest their findings can’t be explained by any other known MS risk factors. That leaves EBV as the most likely cause.

Scientists at Stanford Medicine claim their study is the first to “definitively” show that EBV can trigger MS in some people.

These studies support the idea that antiviral drug treatments that target EBV may be able to treat MS.

Right now, one of the best treatments for MS is something called anti-CD20 monoclonal antibodies. That’s a treatment that lowers immune cells called memory B cells, which is where inactive EBV mainly lives. When you get rid of those white blood cells, you also clear out at least some inactive EBV infection.

If EBV does cause MS, scientists may be able to use that information to figure out how to prevent MS in the first place. And research from the Stanford study suggests vaccine makers might need to avoid certain antigens, such as EBNA1,  that might trigger an autoimmune reaction.

In the future, people who already have MS may be able to get a “reverse vaccine.” Kind of like an allergy shot, this would teach the immune system to stop attacking GlialCAM in nerve cells.

About 95 percent of people will catch EBV at some point. But most people who are infected don't develop MS. It is rare. On average, MS affects about half of 1 percent of the population. To put it another way, there are more than 332 million people living in the U.S., and around 1 million of those might get MS. But almost all of them will get EBV.

Experts think an EBV infection, such as mono, is a necessary step toward developing MS. But it’s not the only factor. Your genes, biology, environment, and lifestyle also matter.

Your chances of developing MS may go up if you have a mix of the following:

  • You’re female.
  • You have a close family member with MS.
  • You smoke.
  • You have a history of migraine.
  • You have very low levels of vitamin D.

Talk to your doctor about your concerns about EBV and MS. They’ll help you keep an eye on your health. And if you do develop MS, early treatment with medicine can help manage symptoms and may slow disease progress. You may have even more treatment choices.

Not sure if you’ve had EBV? Let your doctor know. A simple blood test can tell you for sure.