NYT Magazine: Epstein Barr Virus and Multiple Sclerosis

February 25, 2022

The New York Times Magazine takes an interesting look at the recent research that revealed a link between Epstein Barr Virus (Mono or Glandular Fever) and Multiple Sclerosis. We reported on the first piece of research that had determined this link, but additional evidence has emerged that explains how EBV triggers MS in some people.

I have again included Dr Shepherd's thoughts on this earlier development which includes how Glandular Fever is regarded as a common trigger for some people who develop ME/CFS. Of course, given the dire lack of good quality research in ME/CFS, we don't know half as much about ME/CFS as they do Multiple Sclerosis or Epstein Barr Virus – even before these studies were published.

It is fascinating to read of the progress being made with Multiple Sclerosis and I hope it leads to effective treatments, but as someone who has had ME/CFS for 22 years, I find it incredibly frustrating to think that similar progress hasn't been made in my disease – which has a greater impact on functional ability, quality of life, and that could be much more common. Why aren't researchers as interested in ME/CFS?

Hopefully, the signifcant investments being made in Long Covid will have a bearing on ME/CFS and provide some desperately-needed answers, but it still doesn't solve the main problems: lack of research interest and lack of funding in ME/CFS. However, if we accept that Glandular Fever is a leading trigger for the devepment of PVFS and ME/CFS, then the possibility of a vaccine for Epstein Barr Virus (see below), might at least prevent ME/CFS occurring in some people in the future – which would be a very good development indeed.

STUDIES SHOW The Strange Connection Between Mono and M.S.

New research proves a virus – one that almost all of us have – “causes” multiple sclerosis.

By Kim Tingley Feb. 23, 2022


We now know that upward of 90 percent of adults have the Epstein-Barr virus. As happens with other herpes​viruses, once you have been infected, the virus stays with you forever — it deposits its DNA alongside yours in the nucleus of many of your cells. (RNA viruses, like SARS-CoV-2, can be cleared from your body.) Most people contract Epstein-Barr in childhood: It is spread through body fluids, usually saliva; kissing is a frequent route of transmission (as may be the sharing of utensils). Young children, if they get sick at all, typically develop symptoms indistinguishable from those of a cold or flu; mono is more common when the first infection happens after puberty. “Most people never know they’re infected,” says Jeffrey Cohen, the chief of the Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases.

“In practical terms, if you’re not infected with E.B.V., your risk of M.S. is virtually zero,” says 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.” The odds of that increase having occurred by chance are less than one in a million.

NYT Magazine.

The virus enters cells at the back of the throat and from there moves into B cells, a type of white blood cell that produces antibodies. In some B cells, the virus replicates, making proteins that the immune system can recognize and subdue. In other cells, though, it remains dormant. “It’s very stealthy,” Cohen says. Ultimately, as those infected B cells circulate throughout the body, they reach the back of the throat again. The virus awakens and starts producing proteins, which its host sheds, potentially spreading the pathogen to others, probably for several days each month. “The vast majority of people who are infected are passing it around,” Cohen says. “It’s shed in our saliva the rest of our lives.”

Scientists have long hypothesized that viruses, including Epstein-Barr, are involved in the development of autoimmune diseases, in which the immune system mistakenly attacks healthy tissue. Evidence links it to lupus, and a recent study reported that people with long Covid were more likely than others to have an active Epstein-Barr infection (though it is unclear whether that infection causes symptoms, because the virus can proliferate when the immune system is under stress without creating any health problems)…

New research and possible treatment

Just over a week after the Science paper came out, Robinson and colleagues published their own paper in Nature that demonstrated how the virus triggers the disease in some people. Epstein-Barr produces proteins that mimic a protein in the myelin sheath, they found; when the immune system makes antibodies to attack the virus, they also attack the myelin — “the insulation around your neurons,” as Robinson puts it. “Like electrical wires, if the insulation gets stripped off, it short-​circuits,” he says. “That’s what results in M.S.”

This protein mix-up, though, can only explain about a quarter of M.S. cases. And while the Science paper concludes that Epstein-Barr is the “leading cause” of M.S., Cohen says he wants to be careful with the word “cause.” He thinks the study proves that the virus is a necessary precondition for M.S., but the fact that so many people have Epstein-Barr and so few of them get M.S. demonstrates that other factors, very likely including genetic susceptibility, must play a significant role in the development of the disease. Still, similar hard-to-disentangle circumstances describe other diseases for which most people do feel comfortable pointing to a specific culprit. The C.D.C. refers to polio as “a disabling and life-threatening disease caused by the poliovirus,” for instance, but fewer than five in a thousand people who contract the virus develop serious symptoms.

What is exciting about the discovery that Epstein-Barr is necessary for M.S. is that it raises the prospect that a vaccine could prevent that diseaseas well as other serious conditionseven if we never understand precisely why the virus behaves as it does in a given individual. As long as the link between Epstein-Barr and M.S. remained controversial, commercial and popular interest in such a vaccine was “lukewarm,” says 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, an Epstein-Barr disease research group that hopes to begin clinical trials of a vaccine this year. “Now I think things will change.”

ME Association comment on the initial research

This is a very large and impressive research study that has examined whether Epstein Barr virus (EBV), the virus that causes glandular fever, also plays a role in causing multiple sclerosis (MS). A link between EBV and MS has long been queried and there is already some evidence to support this. These results add considerable weight to this hypothesis.

We also know that EBV is a causal factor in a number of malignant conditions including Burkitt's lymphoma (a tumour of the lymphatic system where the body makes an abnormal type of white blood cell called B cells), Non Hodgkin’s lymphoma and nasopharyngeal carcinoma (the nasopharynx connects the back of the nose to the throat).

In relation to ME/CFS, it is also of interest because EBV/glandular fever is probably the most common viral trigger factor for a post-viral fatigue syndrome (PVFS) and ME/CFS in adolescents – where it is thought about 10% of adolescents develop either a persisting PVFS or ME/CFS following glandular fever. EBV is also a virus that can remain dormant in the body after the initial infection and can then become reactivated.

And there is some evidence (not always consistent) that EBV reactivation occurs in ME/CFS – which can be read here. Further information on the links between EBV and ME/CFS in relation to acting as a trigger factor and the reactivation of a dormant infection is summarised and referenced in the Research/Infection section of the ME Association ME/CFS/PVFS Clinical & Research Guide (also known as the MEA purple book).

Dr Charles Shepherd,
Trustee and
Hon. Medical Adviser
to the ME Association.
Member of the 2018-2021 NICE Guideline Committee.
Member of the 2002 Independent Working Group on ME/CFS.

Dr Charles Shepherd
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