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Is EBV really the cause of MS?

Big and exciting news came out early this year: a study published in ‘Science’ shows that Epstein-Barr virus (EBV) may be the leading cause of MS.

Our expert Dr. Adrian-Minh Schumacher answers six important questions that you might have.


  1. What is the Epstein-Barr Virus
  2. How can a virus cause an autoimmune disease?
  3. Didn’t we already know that EBV causes MS?
  4. What is so special about the new study?
  5. How can I protect myself from EBV?
  6. Does this mean anything to me as an MS patient?

What is the Epstein-Barr Virus?

EBV is the virus causing ‘mono’, a disease mostly occurring in teenagers (also known as infectious mononucleosis, glandular fever or kissing disease). Many of us get infected before their teenage years and suffer a minor illness or don’t show any symptoms at all.

After infection the virus goes into an inactive, hibernating state. This is why 90-95% of adults carry the virus without noticing it. And of course not all go on to get MS.


How can a virus cause an autoimmune disease?

An autoimmune disease is complex. Whether or not a disease occurs is dependent on two things; genetic and environmental factors, and triggers.

The presence of genetic and environmental factors determine how likely someone is to get a disease (their risk level) and then the trigger (for example a virus) is what could ultimately start the onset of disease.

EBV as a trigger for MS

Here, we will look at the Epstein-Barr virus in its role as a trigger. Please keep in mind that it does not have to be the only trigger. And all the risk factors like smoking, low vitamin D etc. still remain important.

What is most important here is that the new research shows that EBV could be quite a strong trigger.

So what is it about the Epstein-Barr virus that would make it so important with regards to MS? Well, it is about the way it behaves. EBV ‘hibernates’ in our bodies once we get infected with it. This is also why even though most of us carry the virus, we do not show any symptoms of active infection.

More specifically, it hijacks certain cells of our immune system: memory B-cells. And in MS, it is exactly those cells that we suspect to be responsible for the bouts of inflammation we see in relapses. As well as the chronic, low-level inflammation, which is what is happening in progressive disease.

There are several theories on how this exactly works, and we are still missing a few puzzle pieces. But the overall hypothesis is that EBV-infected B-cells can be an important driver of MS, because the virus changes the way they function.


Didn’t we already know that EBV causes MS?

In a way, yes, the scientific community has been researching this topic for many years. And many links have been established so far.

For instance, almost all MS patients test positive for EBV.

Remember: 2-5 % of the general population do remain negative for the virus. So that would be a strange coincidence that none of them are MS patients. Also, the risk of developing MS was already shown to be much higher after suffering mono.

These hints do not necessarily mean that EBV is the leading cause. It could be a coincidence, or a byproduct of MS itself. The only way to prove that EBV is the cause of MS would be the following experiment:

  1. Take a large group of young people negative for EBV,
  2. Prevent an EBV infection in randomly selected participants.
  3. Give the others a placebo.
  4. After a few years you see at how many eventually develop MS.

If there is fewer or no MS cases in the prevention group, then we would know that EBV causes MS. Sounds feasible, so why hasn’t this been done yet?

There is one problem: we currently can’t prevent EBV infections.


4. What is so special about the new study?

The new study in ‘Science’ that just came out made it into many news headlines. But even though the EBV hypothesis is not new, the way the study addressed this issue has been done in a very smart way.

Studying health data from the US military

The researchers from Harvard University looked at blood samples and health data from the US military, where soldiers get frequent examinations. In principle, these mostly young soldiers are a healthy bunch. But still, some of them would eventually get sick with MS during their time in the military.

As the soldiers were regularly monitored, the scientists could assess the EBV status of these patients over time, most importantly, before they got MS.

Their results showed that if someone was negative for EBV in the first exam they got, i.e. when entering the military, and then over time got positive for EBV, the likelihood of MS increased.

The increase wasn’t insignificant either, it was 32 times higher. This is an extremely big increase in risk.

The study didn’t stop there, they also looked into the sequence of events. They checked whether they could detect any changes in the blood samples which can indicate MS. They measured for increased neurofilament which is a key marker of MS. Sometimes these alterations can be detected months or years before the first symptoms of MS.

The study found that they could see an increase in neurofilament before the onset of MS. However, only after EBV infection.

This means that EBV infection always happened before any sign of MS, either symptoms or increased neurofilament in the blood samples.

To show this sequence:

EBV -> Neurofilament -> MS

is a really big step forward when talking about EBV as a cause for MS.


How can I protect myself from EBV?

Unfortunately for most of us, it is too late. We are already infected with EBV. And especially so, if you happen to have MS. The situation might be looking different for a newborn baby.

The first, early-stage EBV vaccine trial is currently recruiting. So there is a chance that we might have another important vaccine to give children in the future. However we can not be sure yet whether this will work safely and efficiently.

If you want to protect your kids from getting MS, focus on the following risk factors for now: prevent smoking, sufficient levels of vitamin D throughout childhood and adolescence and avoiding overweight or obesity.


Does this mean anything to me as an MS patient?

Yes, it certainly does. I am sure this will strongly stimulate research on new therapies. One key influence is that researchers are more confident about the hypothesis that EBV infected B-cells are a central disease driver.

As you might know, a large part of MS patients receive a therapy which gets rid of these B-cells altogether, e.g. Ocrelizumab or Rituximab. A big advancement would be to target those B-cells more precisely - or even just the EBV-infected ones.

We understand B-cell biology much better nowadays, and the most promising MS therapies that are currently in the drug discovery pipeline are mostly B-cell targeted. So we can expect to get more specific and safer therapies in the longer run.

Let's hope we get lucky soon!


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Sources

Original articles:

  1. Bjornevik, K., Cortese, M., Healy, B.C., Kuhle, J., Mina, M.J., Leng, Y., Elledge, S.J., Niebuhr, D.W., Scher, A.I., Munger, K.L., et al. (2022). Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science.
  2. Bar-Or, A., Pender, M.P., Khanna, R., Steinman, L., Hartung, H.-P., Maniar, T., Croze, E., Aftab, B.T., Giovannoni, G., and Joshi, M.A. (2020). Epstein–Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies. Trends Mol Med 26, 296–310.
  3. Ascherio, A., and Munger, K.L. (2015). Epstein Barr Virus Volume 1, One Herpes Virus: Many Diseases. Curr Top Microbiol 390, 365–385.

Commentary:

  1. https://dgn.org/presse/pressemitteilungen/multiple-sklerose-durch-das-epstein-barr-virus-kommt-die-ms-impfung/
  2. https://gavingiovannoni.substack.com/p/more-evidence-that-ebv-is-the-cause