Epstein-Barr virus may be leading cause of multiple sclerosis: study

In green leukemia cells infected with Epstein-Barr virus.

In green leukemia cells infected with Epstein-Barr virus.
Photo: CDC / Dr. Paul M. Feorino

Researchers say they have found striking evidence that a common infection caused by the Epstein-Barr virus is the leading cause of multiple sclerosis. Their research have found that military personnel who were recently tested positive for the virus continued to have a significantly higher risk of later developing multiple sclerosis than those who did not. The results seem to support the need for a preventative vaccine or treatments that can directly target the typically lifelong latent infection.

Multiple sclerosis is a rare but disabling condition neurological disorder which is thought to affect about 1 million people in the United States. Those with multiple sclerosis have an overzealous immune system that eats away at the protective coating of our nervous system, known as myelin. Over time, the lack of myelin slows down and damages the connections between our brain and body, leading to a number of symptoms such as numbness, muscle weakness, pain and difficulty walking.

Multiple sclerosis progresses differently from person to person after the first flare-up, and most people will initially avoid symptoms and cope with neurological damage for months or years at a time between relapses. However, about 10% to 20% of people with multiple sclerosis have to live with constant and often worsening symptoms, while some with the recurrent form of multiple sclerosis will eventually stop having periods of remission. In the most severe cases, people lose their ability to write, speak and walk, and even the average patient has a shorter life expectancy.

There is no clear established cause of MS, although it has long been suspected that certain viral infections may be the first trigger for many cases. And one of the most prominent suspects has been Epstein-Barr virus (EBV).

EBV is a herpes virus that is transmitted by almost everyone at some point in their lives. The infection does not usually make children sick, but when caught in adolescence or adulthood, it is one of the leading causes of infectious mononucleosis or mono – an acute illness that causes fatigue, fever and sometimes rashes for about two to six years. weeks. After the first disease, however, the virus lies dormant in our body and usually does not cause visible problems again, although it can do so in people with weakened immune systems.

Some evidence has suggested an association between EBV and multiple sclerosis, which has included finding traces of EBV in the lesions caused by the disorder. But a major stumbling block to establishing a clear cause-and-effect relationship between the two is that because EBV is so common, it can be difficult to find people before they become infected and track them over time to see, whether they develop MS, and compare their risk with people who do not catch the virus. This new research, published Thursday in Science, seems to have achieved just that.

The research team, led by researchers at the Harvard TH Chan School of Public Health, was able to track the long-term health of about 10 million active military members thanks to a 20-year collaboration with the U.S. military. At the start of their service, these members have their blood screened for HIV and are then screened regularly every two years. This meant that the researchers could also test the same blood samples for EBV.

During the 20-year study period, 955 people were diagnosed with multiple sclerosis during their service. Of the 801 MS cases that had testable blood tests, only one did not test positive for EBV antibodies. The team also looked at 35 people who later developed multiple sclerosis but who were negative for EBV at the start of their military service, and they were compared with controls who also tested negative for the virus and did not develop multiple sclerosis. All but one of these people contracted the virus before their final diagnosis of MS. In contrast, persons in the control group who never developed MS were also less likely to have caught EBV during the study period.

According to study author Marianna Cortese, the associated risk of developing MS was 32 times higher in those who got the virus than in those who avoided infection – a difference so high that it would be incredibly unlikely that it was just a coincidence and one who “provides compelling evidence of causality,” she said in an email.

“A risk of this magnitude is unusual in scientific research. The strength of this result and other aspects of the study and the results indicate that this can not be explained by other risk factors and make us sure that EBV is the leading cause of MS, “Cortese added.

Using the same blood tests, Cortese and her team were also able to look for the presence of markers associated with neuroaxonal degeneration, a sign of MS that may appear long before symptoms do. And again, they found that these markers in MS patients who were initially negative for EBV only appeared after the virus had infected them, giving more support to a causal relationship. Nor did they succeed in finding any similar link between MS and human cytomegalovirus, another very common herpes virus, which further suggests that there really is something crucial about the role that EBV plays in multiple sclerosis.

Because EBV is so common, but multiple sclerosis is so rare, there are likely other important factors that affect a person’s risk, including genetics. There was also a case of MS found in a person without a previous EBV infection, which could mean that other infections are a less common trigger. However, the results of the study, provided they are validated by other research, have some important implications for how we handle EBV in the future.

“If EBV is the leading cause of MS, then the disease can be prevented by preventing EBV infection, for example with a vaccine,” Cortese noted. “Additionally, targeting the virus with EBV-specific drugs may lead to better treatment of the disease.”

It would not be the first vaccine developed for a germ to prevent a separate but connected condition along the way. The HPV vaccine is already begins to prevent many cases of cervical cancer in the first women who got it.

There is also some evidence that latent EBV infections can affect the course of MS symptoms. Currently, one of the most effective treatments for multiple sclerosis is anti-CD20 monoclonal antibodies, which depletes the body’s supply of circulating memory B cells that can attack the nervous system. However, these cells are also where EBV hides, so it is possible that some of the benefits of these drugs may come from getting rid of EBV. And if so, then developing antiviral agents that can directly target EBV may be a better strategy than these antibodies, which need to be administered intravenously and weaken the immune system.

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