Epstein-Barr Virus and Multiple Sclerosis: The Viral Thread Connecting Them

Consider an ordinary young woman, she is 25, a technology professional, and an avid runner. Around February 2022, she felt unreasonably tired and a certain numbness in her limbs. She misunderstood these symptoms as the side effects of her rather rigorous training schedule and marched on. However, the numbness worsened and so did her eyesight. It was time to visit the doctor. Some tests were run and she was revealed to be suffering from multiple sclerosis (MS). A closer look at her medical history revealed a seemingly irrelevant detail: she had suffered from a bout of infectious mononucleosis during her college days. It had been caused by the Epstein-Barr Virus.

Her case isn't isolated. A vital study published in Science in January of 2022 examined more than ten million American military personnel to find that individuals infected with EBV were 32 times more likely to develop MS. The evidentiary value of studies results was significant. There was now, compelling proof to substantiate the long-held suspicion that EBV had a part to play in MS. For decades, medical researchers observed prior EBV infections in almost all MS patients but this wasn't sufficient to prove causation. Improved epidemiological methods and large-scale cohort studies, like the one led by Dr Alberto Ascherio at Harvard, helped decisively establish and elucidate this relationship.

Prior research by pioneers such as Dr Lawrence Steinman greatly improved the scientific comprehension of MS. He studied the immunological aspects of the disease revealing important facts about its pathogenesis leading the road to innovative and effective treatment development.

Epstein-Barr Virus (EBV) infection and Multiple Sclerosis (MS) are two distinct medical conditions, but the connection between the two is notable. EPV is one of the most common human viruses and it belongs to the herpes family. It typically causes infectious mononucleosis ideally during childhood or adolescence and very often goes entirely unnoticed due to its mild symptoms. 'Mono' is the only known illness it causes with symptoms including fever, fatigue, swollen lymph nodes, sore throat etc. An interesting fact about EBV is that the virus can remain dormant within the human body for our entire lifespan, periodically reactivating without causing any noticeable symptoms.

MS is an autoimmune illness adversely affecting the central nervous system. The immune system mistakes the myelin sheath (an insulating protective cover surrounding the nerve fibres) as a foreign entity and attacks it. This disrupts the communication between the brain and the rest of the body hampering vision, weakening muscles, impairing balance and coordination, and numbness. Young adults are primarily affected with women constituting the lion's share of the patients. It has no cure and the cause is uncertain. Treatments do exist, however, to help manage the symptoms.

A very high number of MS patients have had EBV infections. Most studies suggest that almost every single patient with MS has had EBV exposure at some point in their life. Why do we think they're connected? EBV's characteristic dormancy and reactivation is one reason. The other is the virus's ability to alter the immune response to increase susceptibility to autoimmune illnesses like MS. Adolescent infections are more likely to develop into MS later in life than infections in childhood, it appears based on some studies.

It is now decisively established that MS cannot develop without prior EBV infection. But how exactly does it exacerbate the development of MS?

EBV exploits the genetic vulnerability of certain individuals by infecting self-attacking B-cells which in turn enter the brain and produce damaging antibodies. These B-cells also produce signals that keep self-attacking T-cells alive which should ideally die by programmed cell death. The likelihood of developing MS after EBV infection depends on a genetic shortage of CD8 T cells, which combat EBV in the body. CD8 T cells are boosted by sunlight and vitamin D to further combat MS.

A pragmatic biotechnology-based solution has since emerged: adoptive T-cell therapy. EBV remains hidden in particular immune cells (B cells ) and causes an abnormal immune reaction, paving the way for MS development. Adoptive T-cell therapy involves extracting a patient's T-cells, increasing their ability to control EBV, and reintroducing them into the body. These new and improved T-cells can better target EBV-infected B-cells, thereby mitigating the infection.

Early studies are promising, with most MS patients who received treatment feeling better and less tired. The more aggressive the T-cells against EBV were, the better the treatment outcomes. There may be more than one way to tackle MS involving antivirals, gene-editing, and the radical new 'inverse vaccine' by Chicago's Pritzker School of Molecular Engineering.

An inverse vaccine does the opposite of a conventional vaccine. Rather than stimulating the immune system, it suppresses autoimmune responses by encouraging immune tolerance. Inverse vaccines deliver antigens linked to carrier proteins or nanoparticles to induce regulatory T-cells to disable self-attacking T-cells. In MS, such vaccines particularly target and prevent the immune attack on myelin without hampering overall immune function.

This matter is still developing. Many possible and effective solutions are likely to emerge shortly.