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

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...

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Autores principales: Charvet, Benjamin, Pierquin, Justine, Brunel, Joanna, Gorter, Rianne, Quétard, Christophe, Horvat, Branka, Amor, Sandra, Portoukalian, Jacques, Perron, Hervé
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558138/
https://www.ncbi.nlm.nih.gov/pubmed/33770381
http://dx.doi.org/10.1007/s12250-021-00372-0
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author Charvet, Benjamin
Pierquin, Justine
Brunel, Joanna
Gorter, Rianne
Quétard, Christophe
Horvat, Branka
Amor, Sandra
Portoukalian, Jacques
Perron, Hervé
author_facet Charvet, Benjamin
Pierquin, Justine
Brunel, Joanna
Gorter, Rianne
Quétard, Christophe
Horvat, Branka
Amor, Sandra
Portoukalian, Jacques
Perron, Hervé
author_sort Charvet, Benjamin
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12250-021-00372-0.
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spelling pubmed-85581382021-11-15 Human Endogenous Retrovirus Type W Envelope from Multiple Sclerosis Demyelinating Lesions Shows Unique Solubility and Antigenic Characteristics Charvet, Benjamin Pierquin, Justine Brunel, Joanna Gorter, Rianne Quétard, Christophe Horvat, Branka Amor, Sandra Portoukalian, Jacques Perron, Hervé Virol Sin Research Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12250-021-00372-0. Springer Singapore 2021-03-26 /pmc/articles/PMC8558138/ /pubmed/33770381 http://dx.doi.org/10.1007/s12250-021-00372-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Charvet, Benjamin
Pierquin, Justine
Brunel, Joanna
Gorter, Rianne
Quétard, Christophe
Horvat, Branka
Amor, Sandra
Portoukalian, Jacques
Perron, Hervé
Human Endogenous Retrovirus Type W Envelope from Multiple Sclerosis Demyelinating Lesions Shows Unique Solubility and Antigenic Characteristics
title Human Endogenous Retrovirus Type W Envelope from Multiple Sclerosis Demyelinating Lesions Shows Unique Solubility and Antigenic Characteristics
title_full Human Endogenous Retrovirus Type W Envelope from Multiple Sclerosis Demyelinating Lesions Shows Unique Solubility and Antigenic Characteristics
title_fullStr Human Endogenous Retrovirus Type W Envelope from Multiple Sclerosis Demyelinating Lesions Shows Unique Solubility and Antigenic Characteristics
title_full_unstemmed Human Endogenous Retrovirus Type W Envelope from Multiple Sclerosis Demyelinating Lesions Shows Unique Solubility and Antigenic Characteristics
title_short Human Endogenous Retrovirus Type W Envelope from Multiple Sclerosis Demyelinating Lesions Shows Unique Solubility and Antigenic Characteristics
title_sort human endogenous retrovirus type w envelope from multiple sclerosis demyelinating lesions shows unique solubility and antigenic characteristics
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558138/
https://www.ncbi.nlm.nih.gov/pubmed/33770381
http://dx.doi.org/10.1007/s12250-021-00372-0
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