Up-to-date knowledge about the association between multiple sclerosis and the reactivation of human endogenous retrovirus infections

Abstract

Only three out of the 70 reviewed sources did not find provide evidence linking the reactivation of HERV and MS progression. On the other hand, overwhelming pieces of evidence confirm that the reactivations often drive the demyelinating plaques by initiating microglial inflammation. Pathological examinations reveal that the inflammatory monocytes (Ly6ChiCCR2 + CX3CR1lo) trigger the reactivation of the malignant T cells that are responsible for the progression of MS. These findings are promoting new discoveries as far as managing MS is concerned.

Viral infections and multiple sclerosis

“…The findings would suggest that HERV activation might trigger a demyelination process, contributing to MS progression [97]. HERVs can be activated by several simuli, including viruses such as VZV, HSV-1, EBV and HHV-6 [98], however the most widely studied association is with EBV.…”

HERV and Epstein-Barr Virus: Another Piece to Multiple Sclerosis Puzzle

“…After Toll Like Receptor 4 (TLR 4) recognition, HERV-W env can activate innate immune response, especially macrophages and microglia, resulting in major inflammation [Arneth 2018;Bahrami 2018;Grandi 2018;Kremer et al 2019]. HERVs mostly leads to M1 macrophages stimulation, the proinflammatory phenotype; more than the antiinflammatory ones, M2 [Arneth 2018. M1 macrophages leads to reactive oxygen, nitrogen species and inflammatory cytokines release, and microglia cells also produce proinflammatory molecules [Kremer et al 2019].…”

“…MS has several unique factors, such as its classical association with higher latitudes, intriguing pathology, women preponderance and a widely variety of clinical presentations [Lassman 2019;Kantarci 2019;Noubarksh 2019]. The disease has three phenotypes: Remittent Relapsing (RRMS), Primary Progressive (PPMS) and Secondary Progressive (SPMS) [Dobson 2018; Arneth 2018].…”

“…HERV proteins are usually inactive, but they seem to play an important role in several diseases (multiple sclerosis, neoplasm, Systemic Lupus Erythematosus [Manghera 2014]) and even non-pathological events, which is the case of HERV-W syncytin-1 (7q21.2 [Grandi 2018]), that contribute to placental formation due its fusogenic potential [Garcia-Montojo 2018]. Interestly, Garcia-Montojo et al demonstrated that Multiple Sclerosis patients have higher levels of syncytin-1 than control group, besides presenting activated phenotype in syncytin-1 expressing cells --monocytes, lymphocytes (both T and) and Natural Killer --and elevated levels of this protein in monocytes during MS relapses [Garcia-Montojo et al 2020].HERVs are divided into families, of which HERV-W has a vaster literatureGrandi 2017;Grandi 2018] of correlation with MS; although HERV-H, HERV-Fc1 and HERV-K are also described in the disease[Morandi et al 2017].HERV-W is believed to be the most involved in MS pathogenesis, and it probably happens because of its components, MSRV and ERVWE[Arneth 2018; Bahrami 2018].Mameli et al have described these two components, whose ORFs origin MSRVenv (HERV-W env) and syncytin-1, respectively[Mameli et al 2009]. MSRV (MS-associated Retrovirus) may induce T cells responses and proinflammatory cytokines release[Arneth 2018;Mameli et al 2009].In 2002, Dolei et al described a cohort of 113 individuals of Sardinian origin, 39 of them having MS diagnosis.…”

ALSUntangled 45: Antiretrovirals

“…HERV expression is also increased in a number of other neurological (7,28,29) and non-neurological diseases, such as cancer (30). Furthermore, some think that HERVs may play beneficial roles in the pathophysiology of certain diseases (31); however, this may not be the case in all diseases as research on multiple sclerosis has suggested a pathogenic role for HERVs (32,33).…”