title: Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: GeNeuro, Geneva, Switzerland. hp@geneuro.com
authors.forename: Hervé
authors.initials: H
authors.lastname: Perron
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Germi
authors.forename: Corinne
authors.initials: C
authors.lastname: Bernard
authors.forename: Marta
authors.initials: M
authors.lastname: Garcia-Montojo
authors.forename: Cécile
authors.initials: C
authors.lastname: Deluen
authors.forename: Laurent
authors.initials: L
authors.lastname: Farinelli
authors.forename: Raphaël
authors.initials: R
authors.lastname: Faucard
authors.forename: Francisco
authors.initials: F
authors.lastname: Veas
authors.forename: Ilias
authors.initials: I
authors.lastname: Stefas
authors.forename: Babs O
authors.initials: BO
authors.lastname: Fabriek
authors.forename: Jack
authors.initials: J
authors.lastname: Van-Horssen
authors.forename: Paul
authors.initials: P
authors.lastname: Van-der-Valk
authors.forename: Claire
authors.initials: C
authors.lastname: Gerdil
authors.forename: Roberta
authors.initials: R
authors.lastname: Mancuso
authors.forename: Marina
authors.initials: M
authors.lastname: Saresella
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
authors.forename: Sébastien
authors.initials: S
authors.lastname: Marcel
authors.forename: Alain
authors.initials: A
authors.lastname: Creange
authors.forename: Rosella
authors.initials: R
authors.lastname: Cavaretta
authors.forename: Domenico
authors.initials: D
authors.lastname: Caputo
authors.forename: Giannina
authors.initials: G
authors.lastname: Arru
authors.forename: Patrice
authors.initials: P
authors.lastname: Morand
authors.forename: Alois B
authors.initials: AB
authors.lastname: Lang
authors.forename: Stefano
authors.initials: S
authors.lastname: Sotgiu
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.forename: Peter
authors.initials: P
authors.lastname: Rieckmann
authors.forename: Pablo
authors.initials: P
authors.lastname: Villoslada
authors.forename: Michel
authors.initials: M
authors.lastname: Chofflon
authors.forename: Jose
authors.initials: J
authors.lastname: Boucraut
authors.forename: Jean
authors.initials: J
authors.lastname: Pelletier
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
mesh_terms: D001921:Brain / Q000821:virology*; D020077:Endogenous Retroviruses; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000821:virology*; D060888:Real-Time Polymerase Chain Reaction; D014759:Viral Envelope Proteins / Q000032:analysis / Q000378:metabolism*
chemical_list: D014759:Viral Envelope Proteins