Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease

• Published in: Multiple sclerosis Vol. 18; no. 12; pp. 1721 - 1736
• Main Authors: Perron, Hervé, Germi, Raphaëlle, Bernard, Corinne, Garcia-Montojo, Marta, Deluen, Cécile, Farinelli, Laurent, Faucard, Raphaël, Veas, Francisco, Stefas, Ilias, Fabriek, Babs O, Van-Horssen, Jack, Van-der-Valk, Paul, Gerdil, Claire, Mancuso, Roberta, Saresella, Marina, Clerici, Mario, Marcel, Sébastien, Creange, Alain, Cavaretta, Rosella, Caputo, Domenico, Arru, Giannina, Morand, Patrice, Lang, Alois B, Sotgiu, Stefano, Ruprecht, Klemens, Rieckmann, Peter, Villoslada, Pablo, Chofflon, Michel, Boucraut, Jose, Pelletier, Jean, Hartung, Hans-Peter
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.12.2012; Sage Publications; Sage Publications Ltd
• Subjects: Biological and medical sciences; Brain - virology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Endogenous Retroviruses; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Medical sciences; Middle Aged; Multiple Sclerosis - blood; Multiple Sclerosis - virology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Real-Time Polymerase Chain Reaction; Research Papers; Viral Envelope Proteins - analysis; Viral Envelope Proteins - metabolism; syncytin; HERV-W; endogenous retrovirus; multiple sclerosis; biomarker; TLR4; MSRV; Human; Nervous system diseases; Multiple sclerosis; Central nervous system; Inflammatory disease; Encephalon; Central nervous system disease; Degenerative disease
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/1352458512441381

Background: The envelope protein from multiple sclerosis (MS) associated retroviral element (MSRV), a member of the Human Endogenous Retroviral family ‘W’ (HERV-W), induces dysimmunity and inflammation. Objective: The objective of this study was to confirm and specify the association between HERV-W/MSRV envelope (Env) expression and MS. Methods: 103 MS, 199 healthy controls (HC) and controls with other neurological diseases (28), chronic infections (30) or autoimmunity (30) were analysed with an immunoassay detecting Env in serum. Env RNA or DNA copy numbers in peripheral blood mononuclear cells (PBMC) were determined by a quantitative polymerase chain reaction (PCR). Env was detected by immunohistology in the brains of patients with MS with three specific monoclonals. Results: Env antigen was detected in a serum of 73% of patients with MS with similar prevalence in all clinical forms, and not in chronic infection, systemic lupus, most other neurological diseases and healthy donors (p<0.01). Cases with chronic inflammatory demyelinating polyneuropathy (5/8) and rare HC (4/103) were positive. RNA expression in PBMC and DNA copy numbers were significantly elevated in patients with MS versus HC (p<0.001). In patients with MS, DNA copy numbers were significantly increased in chronic progressive MS (secondary progressive MS vs relapsing–remitting MS (RRMS) p<0.001; primary progressive MS vs RRMS –<0.02). Env protein was evidenced in macrophages within MS brain lesions with particular concentrations around vascular elements. Conclusion: The association between MS disease and the MSRV-type HERV-W element now appears quite strong, as evidenced ex-vivo from serum and PBMC with post-mortem confirmation in brain lesions. Chronic progressive MS, RRMS and clinically isolated syndrome show different ELISA (Enzyme-Linked Immunosorbent Assay) and/or PCR profiles suggestive of an increase with disease evolution, and amplicon sequencing confirms the association with particular HERV-W elements.