Thus, this analysis provides a neurobiological rationale for a recently completed clinical study in MS patients showing that antibody-mediated neutralization of pHERV-W ENV exerts neuroprotective effects.
The activation and involvement of human endogenous retroviruses W family envelope gene (HERV-W env, also called ERVWE1) have been reported in several neuropsychiatric disorders, including schizophrenia, as well as in multiple sclerosis (MS).
We developed a peptide nucleic acid (PNA) strand invasion technique for the differentiation between multiple sclerosis-associated retrovirus (MSRV) and ERVWE1 sequences, both molecularly similar, belonging to the human endogenous retrovirus HERV-W family.
Two human endogenous retroviruses of the HERV-W family are proposed as multiple sclerosis (MS) co-factors: MS-associated retrovirus (MSRV) and ERVWE1, whose env proteins showed several potentially neuropathogenic features, in vitro and in animal models.
Increased circulating levels of Abs directed against the HERV-W env-su<sub>93-108</sub> and HERV-W env-su<sub>248-262</sub> peptide fragments could serve as possible biomarkers in patients with MS.
Mimicry between syncytin-1, a HERV-W envelope protein that is expressed during placentation, and myelin proteins may also explain the higher prevalence of multiple sclerosis in women.
The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis.
A peptide nucleic acid (PNA)-mediated technique for the discrimination between multiple sclerosis-associated retrovirus and ERVWE1 sequence has been developed.
The objective of this study is to verify whether HIV activates two endogenous retroviruses of the human endogenous retrovirus (HERV)-W family, multiple sclerosis-associated retrovirus (MSRV) and Syncytin-1, whose neuropathogenic and immunopathogenic properties could contribute to HIV-related neurodegeneration.
Quantitative RT-PCR likewise did not reveal differences in MS regarding HERV-W env general transcript or ERVWE1- and ERVWE2-specific transcript levels.
The molecular characteristics of HERV-W env also differ from what was observed in Multiple Sclerosis (MS) and may represent distinct features of the genome of patients with BD and SZ.
In search of links, the expression of HERV-W/MSRV/syncytin-1, with/without exposure to EBV or to EBV glycoprotein350 (EBVgp350), was studied on peripheral blood mononuclear cells (PBMC) from healthy volunteers and MS patients, and on astrocytes, by discriminatory env-specific RT-PCR assays, and by flow cytometry.
By mapping HERV-W env cDNA sequences (n = 332) from peripheral blood mononuclear cells of patients with MS and healthy controls onto individual genomic HERV-W env elements, we identified seven transcribed HERV-W env loci in these cells, including ERVWE1.
The data of MS patients and controls indicated that MSRV and ERVWE1 are both expressed in the brain of MS patients, while only MSRV is present in the blood; MSRV was released in culture by PBMCs of MSRV-producer individuals.
Our analyses reveal that ERVWE1 env-encoding DNA and RNA exhibited increased detection (p < 0.05) and expression (p < 0.01) in the brains of MS patients.
Using transient transfection assays, we observed that the MS-detrimental cytokines TNFalpha, interferon-gamma, interleukin-6, and interleukin-1 activate the ERVWE1 promoter, while the MS-protective interferon-beta is inhibitory.
These observations emphasize the selective induction of syncytin-1 in brain tissue of MS patients but also illustrate the complex dynamics of this retroelement in neuroinflammatory processes.
Syncytin-mediated neuroinflammation and death of oligodendrocytes, with the ensuing neurobehavioral deficits, were prevented by the antioxidant ferulic acid in a mouse model of multiple sclerosis.