The Relationship of the Mechanisms of the Pathogenesis of Multiple Sclerosis and the Expression of Endogenous Retroviruses

Abstract

Two human endogenous retroviruses of the HERV-W family can act as cofactors triggering multiple sclerosis (MS): MS-associated retrovirus (MSRV) and ERVWE1. Endogenous retroviral elements are believed to have integrated in our ancestors’ DNA millions of years ago. Their involvement in the pathogenesis of various diseases, including neurodegenerative pathologies, has been demonstrated. Numerous studies have shown a correlation between the deterioration of patients’ health and increased expression of endogenous retroviruses. The exact causes and mechanisms of endogenous retroviruses activation remains unknown, which hampers development of therapeutics. In this review, we will summarize the main characteristics of human endogenous W retroviruses and describe the putative mechanisms of activation, including epigenetic mechanisms, humoral factors as well as the role of the exogenous viral infections.

HSV-1 and Endogenous Retroviruses as Risk Factors in Demyelination

“…It is established that HERVs are up-regulated in the brain of MS patients compared to healthy controls, and there is a strong epidemiological association between MS and the expression of HERVs [ 28 , 30 , 31 , 91 , 108 , 109 , 110 ]. The HERV-W family is a large group of TEs found in humans and also in non-human primates, and it is mobilized by the LINE-1 machinery [ 111 ].…”

“…MSRV is an important TE belonging to the HERV-W family [ 112 ] that has been linked to MS [ 27 , 30 , 31 ]. It has been proposed as a biomarker for MS behavior and therapeutic outcomes, supported by several facts.…”

“…These elements have been implicated in crucial physiological processes such as placentation [ 17 ], immunity [ 18 , 19 ], and development [ 20 , 21 , 22 ], and their dysregulation can lead to different pathologies [ 16 , 23 , 24 , 25 , 26 ]. Several studies have demonstrated a sound epidemiological relationship between MS and ERVs, which are up-regulated in the brains of MS patients [ 27 , 28 , 29 , 30 , 31 , 32 ]. Herpesviruses have also been associated with regulation of human ERVs (HERVs) [ 26 , 33 , 34 ], and HSV-1 in particular can modulate HERVs in cells involved in MS pathogenesis [ 5 ].…”

Recognize Yourself—Innate Sensing of Non-LTR Retrotransposons

“…In addition, an aberrant expression of HERV transcripts has been observed in various inflammatory diseases and tumor samples. For example, a role of HERV transcripts in autoinflammatory diseases such as multiple sclerosis (HERV-W) or in cancer development (HERV-K) has been suggested (reviewed in [13,14]). In general, HERVs have been highly mutated over the course of millions of years of vertical transmission, and most of the time only solitary LTRs can be detected within the human genome.…”

“…The exact cause for MS is still unclear. Interestingly, among other potential candidates, chronic virus infections (various herpesviruses) as well as an enhanced activity of endogenous retroviruses, such as HERV-W, have been suggested to play a role in triggering the disease [14].…”