Epstein-Barr Virus (EBV) is a widespread human herpesvirus, often acquired during childhood or adolescence. Multiple Sclerosis (MS) is a chronic neurological condition impacting the brain and spinal cord. Recent scientific investigations have revealed a strong connection between prior EBV infection and a heightened risk of developing MS.
Understanding EBV and MS
Epstein-Barr Virus is a common herpesvirus, infecting over 90% of adults globally. While many infections are asymptomatic, EBV can cause infectious mononucleosis, or “mono.” After initial infection, the virus remains latent, primarily within B cells, a type of immune cell. This allows the virus to persist in the body, often without causing further symptoms.
Multiple Sclerosis, in contrast, is an autoimmune disease affecting the central nervous system, which includes the brain and spinal cord. In MS, the body’s own immune system mistakenly attacks myelin, the protective fatty sheath that insulates nerve fibers. This damage disrupts the ability of nerves to transmit signals effectively, leading to a range of neurological symptoms such as vision loss, muscle weakness, numbness, and problems with coordination. The disease can manifest in different forms, with symptoms appearing in distinct attacks or progressing steadily over time.
The Compelling Link Between EBV and MS
Research shows a strong association between prior EBV infection and an increased risk of developing MS. Nearly all individuals with MS have evidence of past EBV infection, with prevalence rates approaching 100% in MS patients, compared to approximately 90% in the general population.
Longitudinal studies provide evidence for this link. A 20-year study of over 10 million U.S. military service members found the risk of MS increased 32-fold after EBV infection. This research also showed that blood levels of neurofilament light chain, a marker of nerve damage, rose only after EBV infection, supporting that EBV exposure precedes neurological damage. While EBV infection is strongly implicated, it is considered a necessary but not sufficient factor for developing MS, meaning other genetic or environmental elements also contribute.
How EBV Might Trigger MS
Scientists propose several mechanisms for how EBV infection could contribute to MS. One hypothesis involves molecular mimicry. This occurs when EBV viral proteins, particularly Epstein-Barr nuclear antigen 1 (EBNA1), share structural similarities with proteins in myelin or other central nervous system components, like GlialCAM. When the immune system fights EBV, it may mistakenly attack these similar host proteins, damaging the myelin sheath. Studies show antibodies in MS patients can bind to both EBNA1 and GlialCAM, supporting this cross-reactivity.
EBV’s ability to persistently infect B cells, a type of immune cell, also contributes to immune dysregulation. EBV establishes latent infection within B cells, expressing different viral genes. This persistent infection can alter B cell behavior, potentially leading to chronic inflammation and autoimmunity. For instance, EBV-infected B cells can accumulate in the brain meninges of MS patients, becoming sites of viral persistence and contributing to immune cell activation and inflammation within the central nervous system. Reactivation of dormant EBV can further trigger immune responses that contribute to MS pathology.
Implications for Prevention and Treatment
The strong association between EBV and MS opens new avenues for prevention and treatment. Developing an EBV vaccine holds promise to reduce MS incidence. Such a vaccine, if administered before initial EBV infection, could prevent the chain of events leading to MS, similar to how vaccines have impacted other infectious diseases. Several EBV vaccine candidates are currently in clinical trials, including mRNA and nanoparticle vaccines, with some aiming to prevent infection and others to induce strong immune responses.
Beyond prevention, understanding this link could lead to new targeted therapies for individuals already living with MS. Researchers are exploring antiviral drugs that specifically target EBV to potentially slow or halt disease progression. For example, a systematic review identified four existing antiviral medications—famciclovir, tenofovir alafenamide, maribavir, and spironolactone—as promising candidates for repurposing to treat EBV in MS. Clinical trials, such as the STOP-MS and FIRMS-EBV trials in Australia, are planned to investigate whether these antivirals can suppress EBV infection and manage MS symptoms like fatigue and progression. This research may also lead to more personalized approaches for treating autoimmune diseases.