An extremely prevalent virus called Epstein-Barr has the capacity to trigger the development of multiple sclerosis (MS) by tricking the body’s immune system into attacking its own nerve cells, according to a new study in the journal Nature. This vital research builds upon a paper published earlier this month, which indicated that most MS cases arise after infection with the virus, and illuminates the mechanism by which the pathogen brings about this debilitating condition.
Thought to be present in the vast majority of human adults, the Epstein-Barr virus (EBV) has long been suspected as a potential cause of MS, yet until very recently scientists had struggled to find solid evidence for this link. However, the connection was finally identified thanks to a massive study involving 10 million US military veterans, which revealed that virtually none developed MS until after they had caught the virus.
Now, researchers have revealed that a particular protein produced by the virus mimics a compound that helps nerve cells to function, and that the antibodies we develop to protect us from EBV can therefore end up damaging our nervous system as well.
“EBV tricks the immune system into responding not only to the virus, but also to this critical component of the cells that make up the white matter in our brains,” explained study author Lawrence Steinman in a statement. “To use a military metaphor, it’s like friendly fire: In fighting the virus, we damage our own army.”
The researchers arrived at this conclusion after analyzing the antibodies present in the blood and spinal fluid of nine MS patients, and determining that the condition appears to be associated with a certain pattern of antibody proteins that are produced by immune cells in the spinal fluid. When they tested these antibodies for reactivity with EBV they found that they had a high affinity for a protein called EBNA1, which makes up part of the virus. Eight of the nine patients studied had antibodies that bound to some fragment of EBNA1.
Further analysis revealed that the same antibody is also able to bind to a separate protein known as GlialCAM, which is found in the myelin sheaths that insulate nerve cells and enable the efficient transmission of electrical impulses. Multiple sclerosis is associated with a loss of myelin, resulting in symptoms including muscle weakness, numbness, and fatigue, and the destruction of GlialCAM by these EBV antibodies therefore represents a clear link between the virus and MS.
“Part of the EBV protein mimics your own host protein – in this case, GlialCAM, found in the insulating sheath on nerves,” said study author William Robinson. “This means that when the immune system attacks EBV to clear the virus, it also ends up targeting GlialCAM in the myelin.”
To confirm this finding, the researchers injected part of the EBNA1 protein into mice that had been bred to suffer from a rodent model of MS. They found that this resulted in an increase in immune cell activity within their central nervous systems, greater demyelination, and more severe paralysis.
It’s worth bearing in mind that while around 95 percent of the global adult population are thought to harbor EBV, only a very small number of people actually develop MS. The researchers say that their findings could lead to the development of more effective treatments for the condition, such as vaccines that specifically target EBV.