Multiple sclerosis: Best evidence yet that condition is caused by Epstein-Barr virus


A huge study of US military personnel suggests almost all cases of multiple sclerosis are triggered by the common Epstein-Barr virus, meaning a vaccine could largely eradicate the condition


13 January 2022

The Epstein-Barr virus viewed under a microscope


It has long been suspected that the common Epstein-Barr virus can trigger multiple sclerosis (MS). Now, a study of 10 million military personnel in the US has shown that virtually every case of MS is preceded by infection with the virus. The finding suggests a vaccine against the Epstein-Barr virus could greatly reduce the incidence of MS.

“This is really a turning point,” says Alberto Ascherio at Harvard University. It should lead to better ways to treat MS as well as help to prevent it, he says.

MS is caused by the immune system attacking the protective sheath that wraps around nerves, leading to symptoms such as difficulty walking that worsen over time.

The Epstein-Barr virus is a kind of herpes virus that spreads mainly via saliva, for instance by kissing or drinking from the same glass. It is the cause of mononucleosis, sometimes known as glandular fever. Initial infections may cause few, if any, symptoms, but once the virus gets into immune cells called B cells, it lurks in them permanently. It can reactivate and cause issues later in life, including various cancers.

The difficulty with demonstrating that the Epstein-Barr virus is the main cause of MS is that 9 in 10 people worldwide is infected with it. This means scientists must monitor huge numbers of people to find out whether people who haven’t been infected with the virus are less likely to develop MS.

Ascherio’s team found the numbers they needed in the form of US military personnel, who have blood samples taken regularly and stored, allowing them to be tested later for Epstein-Barr infections. “This is pretty much unique in the world,” says Ascherio.

Only 5 per cent of recruits were uninfected with the Epstein-Barr virus when their first blood sample was taken. Out of 10 million military personnel, 955 developed MS, typically around 10 years after their first sample was taken.

Yet only one of those who developed MS tested negative for antibodies against the Epstein-Barr virus. Another 34 were uninfected when their first blood sample was taken, but became infected before being diagnosed with MS.

“These findings provide compelling data that implicate Epstein-Barr virus as the trigger for the development of multiple sclerosis,” write William Robinson and Lawrence Steinman at Stanford University, California, in a perspective piece about the study. “Now that the initial trigger for multiple sclerosis has been identified, perhaps multiple sclerosis could be eradicated.”

While there is no vaccine against the Epstein-Barr virus at present, several groups are trying to develop one. On 5 January, Moderna announced that it had begun testing a candidate mRNA vaccine in people.

“Ultimately, we can’t be certain that Epstein-Barr virus is causing multiple sclerosis until we can see what impact preventing Epstein-Barr infection has on multiple sclerosis incidence,” says Clare Walton at the UK’s MS Society.

Finding ways of targeting the virus directly could also improve treatments, says Ascherio. “The presence of the virus provides persistent stimulation to the immune system,” he says.

Indeed, one small trial has already shown that training immune cells called T cells to target the Epstein-Barr virus improved symptoms.

What remains unclear is why so few of those infected with the virus develop multiple sclerosis – less than one in 10,000 in the recruits. “One or more additional factors must be required to trigger multiple sclerosis,” Walton says.

However, it is the norm rather than the exception that only a minority of those infected by a virus experience severe complications, says Ascherio. For instance, only a tiny fraction of those infected with the poliovirus develop the muscle weakness that can cause permanent disability, just as only a small proportion of people infected by the coronavirus end up in hospital. This could be due to genetic factors.

Journal reference: Science, DOI: 10.1126/science.abj8222


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