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‘Smoking Gun’: Study Reveals How Virus May Trigger Multiple Sclerosis

‘Smoking Gun’: Study Reveals How Virus May Trigger Multiple Sclerosis


Posted on January 26, 2024 Updated on January 22, 2024

Epstein-Barr virus, a common virus that infects most people at some point in their lives, has long been suspected as a trigger of multiple sclerosis, an autoimmune disease affecting around 36 people in every 100,000 worldwide.

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But exactly how this virus trips the immune system into attacking the body’s own cells, often years later, has mostly eluded scientists.

Now researchers at the University of Texas have edged one step closer to showing how the virus sets off immune cells in the early stages of MS, when the first symptoms have emerged but patients have not necessarily been diagnosed.

Despite all the threads linking EBV to MS, the virus has taken a while to pin down. Those viral infections generally occur several years before MS emerges, making it difficult for researchers to pinpoint precisely how EBV flips the switch toward MS, in some but not all of those who contract the virus.

MS is an autoimmune condition where the immune system misfires and mistakenly attacks the fatty protective sheath, called myelin, covering nerve fibers in the brain and spinal cord.

Some past research suggests that this happens because of molecular mimicry between EBV proteins that the immune system recognizes as foreign, and molecules found in the brain and myelin of nerve cells, which it shouldn’t.

Confusion ensues: antibodies produced by B cells, a type of white blood cell, bind to the wrong molecule by mistake, tagging it for destruction.

However, B cells are just one agent of the immune system. T cells, another kind of white blood cell, are important soldiers that recognize the alarms of infected cells, presented as distinct protein fragments (called antigens) on their outer surface.

When a T cell recognizes the mark of a foreign invader, an army of T cell clones specific to that particular antigen is produced.

To take a closer look at this part of the immune system, Assaf Gottlieb and colleagues at the University of Texas Health Science Center zoomed in on the interactions between T cells in the blood and cerebrospinal fluid (CSF) of eight people with early symptoms of MS, and lab-grown cells infected with EBV, as well as viral particles.

The researchers compared the T cells’ responses to the Epstein-Barr virus, EBV-infected cells, and other common viruses, including influenza, by sequencing the receptors present on the outside of T cells, to see what they recognized.

In the patients’ blood samples, 13 percent of T cells had receptors recognizing EBV-infected cells, while only 4 percent recognized antigens for the flu.

In the CSF, clones of the T cells recognizing EBV-infected cells had exploded in number, representing 47 percent of the analyzed cells.

These results indicate that T cells made to recognize EBV-infected cells are “present in the CSF at the earliest stages of MS, suggesting that they are likely to play an important role in pathogenesis,” the researchers write in their paper.

“This strongly suggests that these T cells are either causing the disease or contributing to it in some way,” explains J. William Lindsey, study author and UTHealth neurologist. “We have experiments in progress to define what these cells may be doing.”

Other researchers not involved in the work have described the findings as ‘more smoking gun evidence’ for the role of EBV in MS, but we should bear in mind that this is a small study of only eight patients.

However, in equal measure, smaller studies like this are needed to get into the gritty details of potential mechanisms, with the results complementing those of larger studies looking for wider patterns.

Of course, there might well be more to the story. MS isn’t the only condition EBV has been linked to; the virus is also thought to trigger chronic fatigue syndrome (otherwise known as myalgic encephalomyelitis, or ME/CFS).
For such a common virus, it sure does wreak havoc on our health.

The research has been published in PNAS.

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