Ancient Viruses Involved in Multiple Sclerosis

In a study published this week in Embo, scientists from the Institut Pasteur show that ancient viruses are involved in the acute inflammatory defense response that may contribute to multiple sclerosis—an incurable autoimmune disease that leads to irreversible damage to the brain and spinal cord. This disease is also associated with the reactivation of ancient viruses, which were inserted in our DNA during the evolution of humankind. It was therefore long thought that multiple sclerosis was caused by a viral infection.

“Our study shows that reactivation of ancient viruses does not correspond to an infectious phenomenon, but to a defense response of the body when faced with an acute inflammatory phenomenon,” explains senior author Christian Muchardt.

During evolution, viral sequences were neutralized, and they no longer represent a source of infection. But these sequences are a source of external DNA containing information about virus behavior. Cells have, therefore, been able to control these sequences to detect infections as quickly as possible and turn on their defense genes during an attack.

These viral sequences are, above all, used to control defense genes in stem cells. They lie dormant in adult cells, in which more traditional sequences become active. By examining samples from patients with multiple sclerosis, the scientists observed that regulatory sequences of viral origin emerged from their dormant state and were responsible for abnormal expression of several pro-inflammatory genes.

To conclude, in multiple sclerosis, activation of viral sequences does not correspond to an infectious phenomenon but to the unexpected use of regulatory sequences, leading to chronic excessive inflammation. “The discovery of this mechanism, linked to epigenetic phenomena, may one day pave the way for management of MS using small molecules that inhibit chromatin modification enzymes,” Muchardt says.