More evidence a common virus is primary cause of multiple sclerosis

A unique study led by researchers from the Harvard T.H. Chan School of Public Health has reported some of the first robust evidence to affirm multiple sclerosis (MS) is primarily caused by infection from the Epstein-Barr virus (EBV). Tracking more than 10 million US military personnel over a 20-year period, the landmark findings indicate EBV infection leads to a 32-fold increased risk of developing MS.

For decades researchers have suspected the neurological disease MS may be triggered by a viral infection. Just last year a pair of studies identified strong associations between hospital-diagnosed infections before the age of 20 and MS diagnoses after the age of 20. In particular, the research pointed to a distinct link between MS and infectious mononucleosis, also known as glandular fever, a disease caused by the Epstein-Barr virus.

This new study, published in the journal Science, presents the most compelling causal evidence to date indicating EBV infection may be the primary trigger for MS in most individuals. The research utilized a unique dataset from the US military tracking millions of soldiers for two decades.

The study homed in on 801 soldiers who were diagnosed with MS during their service period. All of those cases, bar one, were seen to test positive for EBV before they were diagnosed with MS.

But this in and of itself isn’t surprising. EBV is a stunningly prevalent virus and 95 percent of all people will be infected at some point in their lifetime.

A better indication of causality between MS and EBV came when the researchers looked at 35 MS cases who had initially tested negative for EBV at the beginning of their service but subsequently tested positive at some point before the onset of their MS symptoms. Compared to a control group of soldiers who initially tested negative for EBV and did not go on to develop MS, the research found EBV infection led to a 32-fold increased risk of MS.

The median time from EBV infection to onset of MS was 7.5 years. Some individuals developed MS as soon as two years after an EBV infection, while others didn't develop it for as long as 15 years.

The researchers also looked at the prevalence of other viral infections, particularly cytomegalovirus (CMV), another common virus most people encounter at some point in their lives. There was no association between infections from CMV and the development of MS, indicating there is something specific about EBV infection that could be triggering the onset of MS.

While the new findings offer compelling links between EBV infections and MS development, the big unanswered mystery is exactly how this viral infection is triggering the onset of a neurological disease. An editorial accompanying the new study, from researchers William Robinson and Lawrence Steinman, says the mechanisms underpinning this association remain elusive.

The pair of researchers hypothesize a number of potential ways EBV infection could lead to the onset of MS. EBV proteins may mimic certain brain proteins and trigger an autoimmune response against healthy brain tissue, or EBV infection may directly transform immune B cells, leading to more general immune dysregulation in the years after the acute infection.

It is also important to note the findings do not mean EBV infection is the sole cause of MS. After all, if it were the only cause then 95 percent of the world’s population would ultimately suffer from the devastating disease. Instead, the researchers are keen to stress it is likely a number of genetic and/or environmental factors must be present for a person to be susceptible to MS.

And the new findings affirm it may be the EBV infection that pushes that susceptible person over the line. So while not all EBV infections will lead to MS, all MS cases will likely be preceded by an EBV infection.

And despite the many questions yet to be resolved, this new finding points to some promising new directions for MS researchers. Could directly targeting EBV help treat patients already suffering from MS? Or, perhaps most excitingly, could an EBV vaccine essentially eradicate MS in the first place?

"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,” says Alberto Ascherio, senior author on the new study. "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.”

And an EBV vaccine is far from a hypothetical prospect. Just last week biotech company Moderna announced progress on an EBV vaccine utilizing the same mRNA technology that delivered an effective COVID-19 vaccine. Phase 1 human trials are now underway testing the new vaccine.

The new study was published in the journal Science.

Source: Harvard