Human Endogenous Retrovirus Type W Envelope from Multiple Sclerosis Demyelinating Lesions Shows Unique Solubility and Antigenic Characteristics

Benjamin Charvet, Justine Pierquin, Joanna Brunel, Rianne Gorter, Christophe Quétard, Branka Horvat, Sandra Amor, Jacques Portoukalian, Hervé Perron

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)

Abstract

In multiple sclerosis (MS), human endogenous retrovirus W family (HERV-W) envelope protein, pHERV-W ENV, limits remyelination and induces microglia-mediated neurodegeneration. To better understand its role, we examined the soluble pHERV-W antigen from MS brain lesions detected by specific antibodies. Physico-chemical and antigenic characteristics confirmed differences between pHERV-W ENV and syncytin-1. pHERV-W ENV monomers and trimers remained associated with membranes, while hexamers self-assembled from monomers into a soluble macrostructure involving sulfatides in MS brain. Extracellular hexamers are stabilized by internal hydrophobic bonds and external hydrophilic moieties. HERV-W studies in MS also suggest that this diffusible antigen may correspond to a previously described high-molecular-weight neurotoxic factor secreted by MS B-cells and thus represents a major agonist in MS pathogenesis. Adapted methods are now needed to identify encoding HERV provirus(es) in affected cells DNA. The properties and origin of MS brain pHERV-W ENV soluble antigen will allow a better understanding of the role of HERVs in MS pathogenesis. The present results anyhow pave the way to an accurate detection of the different forms of pHERV-W ENV antigen with appropriate conditions that remained unseen until now.
Original languageEnglish
Pages (from-to)1006-1026
Number of pages21
JournalVirologica Sinica
Volume36
Issue number5
Early online date2021
DOIs
Publication statusPublished - Oct 2021

Keywords

  • Antigen
  • Brain
  • Demyelination
  • Endogenous retrovirus
  • Envelope
  • Glycolipids
  • HERV-W
  • Hexamer
  • Lipids
  • MSRV-ENV
  • Multiple sclerosis (MS)
  • Oligomer
  • Sulfatides
  • Syncytin

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