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The pathogenesis of MS is complex and may relate to various viral conditions. This study analyzes the way that various viruses affect MS onset, and what that can teach us about future therapies.

Compared to other self-limiting myelin disorders, multiple sclerosis (MS) is associated with chronic inflammation in the central nervous system. Although its cause is not fully understood, both genetic and environmental factors are assumed to play a role in increasing risk. MS is often triggered by certain viral infections, notably Epstein-Barr virus (EBV), human herpes virus 6 (HHV-6), human endogenous retrovirus (HERV), cytomegalovirus (CMV), and varicella zoster virus. These viruses’ tropism for the central nervous system and immune cells may partially explain their role in neuroinflammation. This study, published in the Multiple Sclerosis Journal, analyzes the way that different viral infections can change the risk of disease and includes a discussion of strategies by which viruses that play a role in triggering MS can be controlled.

Understanding How Viruses Trigger MS as a Key to New Therapies

Viruses trigger MS in different ways. In the case of EBV, the virus infects naive B cells, which proliferate in germinal centers. Through a chain of events, this results in autoreactive T cells detecting apoptotic myelin fragments by microglia, causing further apoptosis of the myelin sheath and neurons. Effectively controlling the neuroinflammatory effects of EBV has been suggested as one way of treating and preventing MS. Although there are potential targets for developing a vaccine against EBV, none is currently available. IFN-beta, which is one of the best treatments for MS, also inhibits the ability of EBV and other viruses to replicate. The hypothesis that IFN-beta may have overlapping antiviral and anti-inflammatory mechanisms  supports the concurrent testing of MS medications with a variety of modes of action in future studies. 

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Similar approaches for HHV-6, HERV, and CMV are also described. Some of these conditions, such as HERV, can be treated using rituximab to downregulate the expression of the virus by depleting B cells that co-express proteins of EBV and HERV. Relationships between these viruses and MS are also described, including past research  on the prevalence of HHV-6 in patients with MS via brain autopsy. 

Many Viruses May be Involved in the Pathogenesis of MS

The authors conclude that viral infections have potentially significant effects in patients suffering from MS, although a better understanding of their mechanisms of action in the pathogenesis of MS is needed. Because of the heterogeneity of MS, as well as various environmental and genetic variables, the interaction between viruses and MS onset can vary significantly. Some targeting of B cells and memory T cells is common in MS disease-modifying medications, and cell-based treatments that target infected B cells may be a promising future treatment option. Because of the frequency, complexity, and heterogeneity of these viruses, obtaining comprehensive data about plausible treatment pathways is challenging. 


Sedighi, S., Gholizadeh, O., Yasamineh, S., Akbarzadeh, S., Amini, P., Favakehi, P., Afkhami, H., Firouzi-Amandi, A., Pahlevan, D., Eslami, M., Yousefi, B., Poortahmasebi, V., & Dadashpour, M. (2022). Comprehensive Investigations Relationship Between Viral Infections and Multiple Sclerosis Pathogenesis. Current Microbiology, 80(1), 15. https://doi.org/10.1007/s00284-022-03112-z