Working Paper Review Version 2 This version is not peer-reviewed

Human Endogenous Retrovirus as Therapeutic Targets in Neurologic Disease

Version 1 : Received: 8 April 2021 / Approved: 9 April 2021 / Online: 9 April 2021 (13:30:49 CEST)
Version 2 : Received: 9 April 2021 / Approved: 12 April 2021 / Online: 12 April 2021 (12:17:32 CEST)

A peer-reviewed article of this Preprint also exists.

Giménez-Orenga, K.; Oltra, E. Human Endogenous Retrovirus as Therapeutic Targets in Neurologic Disease. Pharmaceuticals 2021, 14, 495. Giménez-Orenga, K.; Oltra, E. Human Endogenous Retrovirus as Therapeutic Targets in Neurologic Disease. Pharmaceuticals 2021, 14, 495.

Journal reference: Pharmaceuticals 2021, 14, 495
DOI: 10.3390/ph14060495


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.


amyotrophic lateral sclerosis; epigenetics; HERV-K; HERV-W; monoclonal antibody; multiple sclerosis; neurodegeneration; temelimab.


MEDICINE & PHARMACOLOGY, Pathology & Pathobiology

Comments (1)

Comment 1
Received: 12 April 2021
Commenter: Elisa Oltra
Commenter's Conflict of Interests: Author
Comment: One of the coauthors is withdrawn due to potential confilct of interest.
Dr. Hervé Perron has manifested his will to be removed as coauthor by written mail to the  corresponding author.
Instead his name has been added to Acknowledgements.
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