Human Endogenous Retrovirus as Therapeutic Targets in Neurologic Disease

Abstract

Human endogenous retroviruses (HERVs) are ancient retroviral DNA sequences established into germline. They contain regulatory elements and encoded proteins few of which may provide benefits to hosts when co-opted as cellular genes. Their tight regulation is mainly achieved by epigenetic mechanisms which can be altered by environmental factors, e.g. viral infections, leading to HERV activation. Aberrant expression of HERVs associates with neurological disease, such as multiple sclerosis (MS) or amyotrophic lateral sclerosis (ALS), inflammatory processes and neurodegeneration. This review summarizes recent advances on the epigenetic mechanisms controlling HERV expression and the pathogenic effects triggered by HERV derepression. The article ends describing new promising therapies targeting HERV elements, one of which, temelimab, has completed phase II trials with encouraging results in treating MS. The information gathered here may turn helpful in the design of new strategies to unveil epigenetic failures behind HERV-triggered disease, opening new possibilities for druggable targets and/or for extending the use of temelimab to treat other associated diseases.

Bisphenols induce human genomic damage and modulate HERVs/env expression

“…Although human retroviruses are not infectious, they can also contribute to the development of the inflammatory condition (Grandi & Tramontano, 2018). Transcriptional activation of HERVs is a common feature in neurodegenerative diseases and human cancers (Giménez‐Orenga & Oltra, 2021; Mao et al, 2021). These may act as cofactors or causative elements that contribute to disease progression and onset (Matteucci et al, 2018).…”