Scientists a step closer to understanding multiple sclerosis with glandular fever link

Strongest evidence yet that Epstein-Barr virus cases MS

A computer illustration of the Epstein-Barr virus. Also known as human herpes virus four, it is one of eight herpes viruses that infects humans. It is best known as the cause of infectious mononucleosis (glandular fever), but is also associated with some forms of cancer, including Burkitts lymphoma. Infection with EBV is common and usually harmless
Powered by automated translation

The virus that causes glandular fever is probably also responsible for multiple sclerosis, research shows, although other factors are likely to be at play too.

The findings on Epstein-Barr virus could, it is hoped, lead to ways to prevent or treat multiple sclerosis, which affects an estimated 2.8 million people worldwide.

The study’s lead researcher, Prof Alberto Ascherio, said that while a link between EBV and MS had been studied for several years, this was the first research providing “compelling evidence” the virus caused the disease.

“This is a big step because it suggests that most MS cases could be prevented by stopping EBV infection, and that targeting EBV could lead to the discovery of a cure for MS,” said Prof Ascherio, who works at the Harvard TH Chan School of Public Health in the US.

All of these herpes viruses cause a latent infection – once you have caught them, you never get rid of them
Prof Ian Jones, University of Reading

The scientists tracked more than 10 million American military personnel, and looked at the relationship between infection with the virus and MS.

The study identified 955 people diagnosed with MS while on active duty. Analysis of blood samples taken by the military every two years showed that EBV infection caused a 32-fold increased risk of developing MS, but other viruses did not make MS more likely.

It has long been suggested that EBV could be one of the causes of MS, said Prof Ian Jones, a professor of virology at the University of Reading in the UK not linked to the new study.

“The principle reason for that is that the typical symptoms of glandular fever, which you get from EBV, are very similar to the sorts of conditions suffered by MS patients, [including] fatigue,” he said.

“All of these herpes viruses cause a latent infection – once you have caught them, you never get rid of them.”

EBV, also known as human herpesvirus 4, spreads easily through saliva or other bodily fluids, and often causes asymptomatic infections in children, according to the US Centres for Disease Control and Prevention.

In teenagers and adults, a symptomatic infection – glandular fever or infectious mononucleosis – is seen more frequently and can lead to tiredness lasing months.

The new study suggests the link between EBV and MS “may be causal”, according to Dr Clare Walton, head of research at the MS Society, a UK charity.

“However, one or more additional factors must be required to trigger MS, as despite nine in 10 people worldwide being infected with EBV, most do not go on to develop MS,” she said.

She added that only when scientists can analyse what impact preventing EBV infection has on the incidence of MS can researchers be certain EBV causes MS.

MS is an autoimmune disease, meaning that it involves the immune system attacking the body’s own cells or tissues.

No vaccine for Epstein-Barr virus yet

In this case, it is the insulating myelin sheath that surrounds nerve fibres that becomes damaged, leading to symptoms that can include numbness or weakness in the limbs, tremors, unsteady gait and problems with vision.

It may be that the immune response that targets EBV proteins may also target proteins in nerve cells or glial cells, which are associated with the nervous system.

The new study, which also involved additional researchers at Harvard as well as at other institutions in the US and Switzerland, has been published in Science, regarded as one of the world’s top scientific journals.

It found that levels in the blood of a substance called neurofilament light chain, a protein that indicates nerve degeneration of the kind seen with MS, increased only after a person had been infected with EBV.

MS often goes undetected early on, which could explain the delay between EBV infection and the onset of MS, Prof Ascherio said.

“Currently there is no way to effectively prevent or treat EBV infection, but an EBV vaccine or targeting the virus with EBV-specific antiviral drugs could ultimately prevent or cure MS,” he added.

However, Prof Paul Farrell, a professor of tumour virology at Imperial College London not linked to the study, cautioned that no EBV vaccine candidate had yet prevented the virus from infecting and persisting in people.

“At this stage it is not clear whether a vaccine of the types currently being developed would be able to prevent the long-term effects of EBV in MS,” he said.

EBV varies in different parts of the world and between ethnic groups, which involves variation in the viral proteins thought to spark the autoimmune response that causes MS.

Sequencing EBV may therefore, Prof Farrell suggested, help explain why some people develop MS after EBV infection and some do not.

Updated: January 16, 2022, 6:51 AM