Endogenous retroviruses in multiple sclerosis: A network-based etiopathogenic model

Abstract

The present perspective article proposes an etiopathological model for multiple sclerosis pathogenesis and progression associated with the activation of human endogenous retroviruses. We reviewed preclinical, clinical, epidemiological, and evolutionary evidence indicating how the complex, multi-level interplay of genetic traits and environmental factors contributes to multiple sclerosis. We propose that endogenous retroviruses transactivation acts as a critical node in disease development. We also discuss the rationale for combined anti-retroviral therapy in multiple sclerosis as a disease-modifying therapeutic strategy. Finally, we propose that the immuno-pathogenic process triggered by endogenous retrovirus activation can be extended to aging and aging-related neurodegeneration. In this regard, endogenous retroviruses can be envisioned to act as epigenetic noise, favoring the proliferation of disorganized cellular subpopulations and accelerating system-specific "aging". Since inflammation and aging are two sides of the same coin (plastic dis-adaptation to external stimuli with system-specific degree of freedom), the two conditions may be epiphenomenal products of increased epigenomic entropy. Inflammation accelerates organ-specific aging, disrupting communication throughout critical systems of the body and producing symptoms. Overlapping neurological symptoms and syndromes may emerge from the activity of shared molecular networks that respond to endogenous retroviruses' reactivation.