Human Endogenous Retroviruses in Neurological Diseases

Küry, Patrick; Nath, Avindra; Créange, Alain; Dolei, Antonina; Marche, Patrice; Gold, Julian; Giovannoni, Gavin; Hartung, Hans-Peter; Perron, Hervé

The causes of multiple sclerosis and amyotrophic lateral sclerosis have long remained elusive. A new category of pathogenic components, normally dormant within human genomes, has been identified: human endogenous retroviruses (HERVs). These represent ∼8% of the human genome, and environmental factors have reproducibly been shown to trigger their expression. The resulting production of envelope (Env) proteins from HERV-W and HERV-K appears to engage pathophysiological pathways leading to the pathognomonic features of MS and ALS, respectively. Pathogenic HERV elements may thus provide a missing link in understanding these complex diseases. Moreover, their neutralization may represent a promising strategy to establish novel and more powerful therapeutic approaches.