A Common Virus Can Trigger Multiple Sclerosis, According to Huge New Study

Multiple sclerosis – an autoimmune disease that affects the brain and spinal cord – can occur after infection with the Epstein-Barr virus (EBV).

According to the clinical source UpToDate, it is estimated that 90 to 95 percent of people become infected with EBV, also called human herpesvirus 4, by adulthood.

In children, the virus usually causes an asymptomatic or very mild infection, but in teenagers and young adults, EBV can cause infectious mononucleosis, better known as “mono.” Despite the fact that EBV is a virus that is often caught, there is evidence to suggest that virus infections are a risk factor for multiple sclerosis, a far rarer condition.

Studies, for example, have shown that people with multiple sclerosis have extremely high levels of antibodies specific to EBV – immune molecules that attach to the virus – compared to those without the disease. And previous research has suggested that catching mono increases the risk of developing multiple sclerosis later in life.

However, given that most people get EBV at some point, it has been difficult to prove that these infections may actually be the underlying cause of multiple sclerosis.

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Now, a new study, published Thursday (January 13th) in the journal Science, provides evidence for this idea. By combing data from about 10 million U.S. military personnel, collected over two decades, the research team found that the risk of developing multiple sclerosis increases 32-fold after EBV infection.

They have not found such a link between autoimmune disease and other viral infections, and no other risk factor shows such a high increase in risk.

The study shows that EBV is clearly linked to the development of multiple sclerosis, while other viruses are not, said Dr. Lawrence Steinman, a professor of neurology and neuroscience at Stanford University School of Medicine who was not involved in the study.

One of the limitations of the research is that it doesn’t explain exactly how EBV can trigger the disease – but other recent work provides strong clues, Steinman told Live Science in an email.

Persuasive evidence

“We have been working on this hypothesis that EBV may be a causal risk factor for MS, for about 20 years,” said Kassandra Munger, co-author of the Scientific Study and senior scientist in the Neuroepidemiology Research Group at Harvard TH Chan School of Public Health.

To test this hypothesis, the team decided to identify individuals who had never been exposed to the virus, monitor their EBV status over time, and see if their chances of developing multiple sclerosis increased after exposure.

Again, “this hypothesis is challenging to test because more than 95 percent of the population is infected with EBV in adulthood,” Munger noted. To identify individuals who had not previously been exposed to EBV, the team combed through a unique data set curated by the U.S. Department of Defense.

The Ministry of Defense maintains a warehouse of serum, a yellowish, liquid portion of blood, sampled by military personnel. At the beginning of their service, and approximately every two years thereafter, active military personnel are given an HIV screening serum, and all remaining serum from the tests is placed in storage.

The serum contains antibodies, so these stored samples provided researchers with a way to check each person’s EBV status over time, checking for antibodies against the virus.

The team then used this data to investigate the potential link between EBV status and the onset of multiple sclerosis. (Of course, their data focused only on those individuals who became exposed in their early 20s, not during childhood.)

Using medical documentation, they identified 801 individuals who developed multiple sclerosis during the study period and who provided at least three serum samples prior to diagnosis.

They found that 35 of these 801 individuals were negative for EBV-specific antibodies at initial serum sampling, but over time all but one subject became exposed to the virus. Thus, 800 of 801 were infected with EBV before developing multiple sclerosis.

The team conducted several tests to determine if another virus had such a strong correlation with the disease, but found that EBV is the only one that stands out in this way.

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The team noted another hint that EBV causes multiple sclerosis: in the serum of those who developed the disease, the team noticed signs of nerve damage that appeared after exposure to EBV, but before their official diagnosis of MS.

In multiple sclerosis, the immune system mistakenly attacks myelin, the insulating sheath that surrounds many nerve fibers, and this damage impairs the ability of nerve cells to transmit signals. Early signs of this nerve cell damage can appear up to six years before the onset of multiple sclerosis, according to a 2019 journal report. PIT; so the team looked for indications of this damage in serum samples.

Specifically, they were looking for a protein called the light chain neurofilament, whose concentrations rise in the blood after nerve cell damage. This protein increased in the serum of those who developed multiple sclerosis, but only after they became exposed to EBV.

For those in the control group, who never developed multiple sclerosis, the light chain neurofilament concentration in the blood remained the same before and after EBV infection; this is in line with the idea that EBV exposure does not promote multiple sclerosis in everyone, but only in vulnerable people.

“The infection appears to occur before there is any evidence of nervous system involvement,” Munger said.

Considering other results of the study, “this is really, we think, convincing proof of causality,” she told Live Science.

“It somehow inextricably links EBV infection and the development of MS,” Robinson said, repeating the opinion.

However, the paper cannot reveal exactly why this connection exists – but a recent study conducted by Robinson and Steinman provides some clues.

The study, published Jan. 11 in the Research Square preprint database, has not yet been reviewed or published in a scientific journal.

This suggests that in people with multiple sclerosis, specific antibody-producing cells appear in large numbers in the fluid surrounding the brain and spinal cord. These cells produce antibodies that attach to an EBV protein called EBNA-1 – but unfortunately, the same antibodies also follow a similar-looking molecule on myelin-producing cells.

Several other studies also provide evidence of EBV-specific antibodies targeting nerve cell components and the myelin sheath itself.

“I think that would be the leading hypothesis, that the viral component looks like its own protein,” and that this striking resemblance drives the immune system to attack myelin, Robinson said.

Of course, even with this growing evidence, one big question remains: if most people get EBV at some point, why do only some people develop multiple sclerosis? The answer lies, at least in part, in their genes.

Evidence suggests that specific versions of genes that regulate the immune system may make a person susceptible to multiple sclerosis, Robinson said.

Within that genetic context, EBV can then ignite a fuse that triggers the development of multiple sclerosis. But perhaps in the future, the EBV vaccine could prevent the wick from ever catching fire, or therapists could counteract the long-term effects of the virus on the immune system, stopping multiple sclerosis, he said.

“Now that the initial trigger for MS has been identified, perhaps MS could be eradicated,” Steinman and Robinson wrote in a comment.

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This article was originally published by Live Science. Read the original article here.

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