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

作　　者：Benjamin Charvet Justine Pierquin Joanna Brunel Rianne Gorter Christophe Que´tard Branka Horvat Sandra Amor Jacques Portoukalian Herve´Perron 

机构地区：[1]GeNeuro Innovation,Lyon 69008,France [2]CIRI,International Center for Infectiology Research,INSERM U1111,CNRS UMR5308,University of Lyon,ENS Lyon,France [3]Universite´Claude Bernard Lyon 1,Lyon 69000,France [4]Department of Pathology,Amsterdam UMC,Location VUMC,1007 MB Amsterdam,The Netherlands [5]ProteinSimple,Abingdon OX143NB,UK [6]Centre for Neuroscience and Trauma,Blizard Institute,Barts and London School of Medicine and Dentistry,Queen Mary University of London,London E12AT,UK

出　　处：《Virologica Sinica》2021年第5期1006-1026,共21页中国病毒学（英文版）

基　　金：supported by GeNeuro SA.

摘　　要：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 highmolecular-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.

关 键 词：Multiple sclerosis(MS) Brain Antigen HERV-W ENVELOPE Endogenous retrovirus MSRV-ENV SYNCYTIN Demyelination Lipids GLYCOLIPIDS Sulfatides Oligomer HEXAMER 

分 类 号：R744.51[医药卫生—神经病学与精神病学]