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

2021 ◽  
Author(s):  
Benjamin Charvet ◽  
Justine Pierquin ◽  
Joanna Brunel ◽  
Rianne Gorter ◽  
Christophe Quétard ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Envelope Protein ◽  
Endogenous Retrovirus ◽  
Brain Lesions ◽  
Human Endogenous Retrovirus ◽  
Soluble Antigen ◽  
Physico Chemical ◽  
Demyelinating Lesions ◽  
Ms Pathogenesis

AbstractIn 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.

scholarly journals Human endogenous retrovirus W in brain lesions: Rationale for targeted therapy in multiple sclerosis

2016 ◽  
Vol 8 ◽  
pp. 11-18 ◽  
Author(s):  
Jack van Horssen ◽  
Susanne van der Pol ◽  
Philip Nijland ◽  
Sandra Amor ◽  
Hervé Perron
Keyword(s):  
Multiple Sclerosis ◽  
Targeted Therapy ◽  
Endogenous Retrovirus ◽  
Brain Lesions ◽  
Human Endogenous Retrovirus

scholarly journals IL-2 and Mycobacterial Lipoarabinomannan as Targets of Immune Responses in Multiple Sclerosis Patients

2020 ◽  
Vol 8 (4) ◽  
pp. 500 ◽  
Author(s):  
Marco Bo ◽  
Magdalena Niegowska ◽  
Jessica Frau ◽  
GianPietro Sechi ◽  
Giannina Arru ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mycobacterium Avium Subspecies Paratuberculosis ◽  
Interleukin 2 ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Slight Reduction ◽  
Multiple Sclerosis Patients ◽  
The Impact ◽  
Ms Pathogenesis ◽  
Future Practice

Interleukin 2 (IL-2) is considered a key player in exacerbating multiple sclerosis (MS). Therapies targeting its receptor have been developed; however, a resolution of the disease and side effects are still an issue of concern. The involvement of other factors, such as Mycobacterium avium subspecies paratuberculosis (MAP) and envelope protein derived from human endogenous retrovirus type W (HERV-Wenv), in MS pathogenesis has been recently suggested. Here, we investigated the levels of antibodies (Abs) directed against IL-2 and HERV-Wenv in 108 MS patients, 34 patients affected by neuromyelitis optica spectrum disorder (NMOSD), and 137 healthy controls (HCs). Our results show increased levels of Abs specific to IL-2 and HERV-Wenv-su antigens in MS vs. HCs (p < 0.0001 for IL-2, p = 0.0004 for HERV-Wenv) and significantly decreased levels in NMOSD vs. MS. The assessment of different 12-month-long therapies on Abs against IL-2, HERV-Wenv, and MAP lipoarabinomannan (LAM) demonstrated the strongest effect on anti-LAM Abs (p = 0.018), a slight reduction of anti-IL-2 Abs, and small variations for anti-HERV-Wenv Abs. These results highlight the conclusion that the impact of therapy is more correlated with selected epitopes than with the therapeutic agent. Screening for anti-IL-2 and anti-HERV-Wenv Abs has a potential as additional future practice to distinguish between symptomatically similar MS and NMOSD.

The neutralizing antibody GNbAC1 abrogates HERV-W envelope protein-mediated oligodendroglial maturation blockade

2014 ◽  
Vol 21 (9) ◽  
pp. 1200-1203 ◽  
Author(s):  
David Kremer ◽  
Moritz Förster ◽  
Tanja Schichel ◽  
Peter Göttle ◽  
Hans-Peter Hartung ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Envelope Protein ◽  
Nitrosative Stress ◽  
Immune Cell ◽  
Neutralizing Antibody ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Stress Reactions ◽  
Induce Stress ◽  
Inflammatory Reactions

Background: The envelope protein (ENV) of the human endogenous retrovirus type W is implicated in inflammatory reactions in multiple sclerosis (MS) but also interferes with oligodendroglial maturation. A neutralizing antibody GNbAC1 has been developed and successfully been tested in clinical trials. Objectives and methods: We stimulated primary oligodendroglial cells with ENV upon preincubation with GNbAC1 and assessed for nitrosative stress and myelin expression. Results: Neutralization of ENV by GNbAC1 reduces its ability to induce stress reactions resulting in a rescue of myelin expression. Conclusions: Beyond immune cell modulation, this monoclonal antibody may therefore help to overcome the oligodendroglial differentiation blockade in MS.

scholarly journals pHERV-W envelope protein fuels microglial cell-dependent damage of myelinated axons in multiple sclerosis

2019 ◽  
Vol 116 (30) ◽  
pp. 15216-15225 ◽  
Author(s):  
David Kremer ◽  
Joel Gruchot ◽  
Vivien Weyers ◽  
Lisa Oldemeier ◽  
Peter Göttle ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Envelope Protein ◽  
Spatial Association ◽  
Myeloid Cells ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Myelinated Axons ◽  
Neuroprotective Effects ◽  
Microglial Polarization ◽  
Underlying Mechanisms

Axonal degeneration is central to clinical disability and disease progression in multiple sclerosis (MS). Myeloid cells such as brain-resident microglia and blood-borne monocytes are thought to be critically involved in this degenerative process. However, the exact underlying mechanisms have still not been clarified. We have previously demonstrated that human endogenous retrovirus type W (HERV-W) negatively affects oligodendroglial precursor cell (OPC) differentiation and remyelination via its envelope protein pathogenic HERV-W (pHERV-W) ENV (formerly MS-associated retrovirus [MSRV]-ENV). In this current study, we investigated whether pHERV-W ENV also plays a role in axonal injury in MS. We found that in MS lesions, pHERV-W ENV is present in myeloid cells associated with axons. Focusing on progressive disease stages, we could then demonstrate that pHERV-W ENV induces a degenerative phenotype in microglial cells, driving them toward a close spatial association with myelinated axons. Moreover, in pHERV-W ENV-stimulated myelinated cocultures, microglia were found to structurally damage myelinated axons. Taken together, our data suggest that pHERV-W ENV-mediated microglial polarization contributes to neurodegeneration in MS. Thus, this analysis provides a neurobiological rationale for a recently completed clinical study in MS patients showing that antibody-mediated neutralization of pHERV-W ENV exerts neuroprotective effects.

scholarly journals Viruses in multiple sclerosis pathogenesis

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Rachael Tarlinton ◽  
Elena Morandi ◽  
Belinda Wang ◽  
Bruno Gran ◽  
Timur Khaiboullin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Risk Factor ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Molecular Mimicry ◽  
Endogenous Retrovirus ◽  
Neurological Dysfunction ◽  
Human Endogenous Retrovirus ◽  
Vitamin D Levels ◽  
Ms Pathogenesis

Multiple sclerosis (MS) is an extremely debilitating auto-immune disease of people characterised by demyelination of the central nervous system and progressive neurological dysfunction. The etiology of the disease is complex (including factors such as genetics, sex hormones and vitamin D levels). The involvement of viral infections as a risk factor in triggering disease has long been suspected and two classes of viruses in particular, the herpesvirus Epstein-Barr virus (EBV) and the Human endogenous retrovirus “W” family (HERV-W) have been the focus of much recent research. Despite near ubiquitious infection (EBV), or integration into the genome as a repetitive element no longer able to function as a virus (HERV-W) a picture is gradually emerging of how these are involved in MS pathogenesis. In the case of EBV, having had infectious mononucleosis (clinical disease in patients infected post-puberty) increases the risk of developing MS. For HERV-W our recent work has confirmed that RNA is over-expressed in MS patients compared with healthy controls (though basal levels vary with ethnic background) and that EBV infection of B cells triggers expression of HERV-W RNA and proteins. There is a growing body of evidence that expression of HERV-W can trigger innate immune system inflammatory responses. There is also increasing evidence for molecular mimicry between epitopes of the HERV-W env protein, the EBV EBNA1 protein and peptides from brain proteins implicated in MS pathogenesis. Crucially these peptides are also able to bind the HLA-DR2b locus that is the strongest genetic risk factor for MS development.

scholarly journals Multiple Sclerosis and Obesity: Possible Roles of Adipokines

2016 ◽  
Vol 2016 ◽  
pp. 1-24 ◽  
Author(s):  
José de Jesús Guerrero-García ◽  
Lucrecia Carrera-Quintanar ◽  
Rocío Ivette López-Roa ◽  
Ana Laura Márquez-Aguirre ◽  
Argelia Esperanza Rojas-Mayorquín ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Early Life ◽  
Neural Tissue ◽  
Autoimmune Disorder ◽  
Susceptibility Factor ◽  
Related Risk ◽  
Inflammatory State ◽  
The Central Nervous System ◽  
Ms Pathogenesis

Multiple Sclerosis (MS) is an autoimmune disorder of the Central Nervous System that has been associated with several environmental factors, such as diet and obesity. The possible link between MS and obesity has become more interesting in recent years since the discovery of the remarkable properties of adipose tissue. Once MS is initiated, obesity can contribute to increased disease severity by negatively influencing disease progress and treatment response, but, also, obesity in early life is highly relevant as a susceptibility factor and causally related risk for late MS development. The aim of this review was to discuss recent evidence about the link between obesity, as a chronic inflammatory state, and the pathogenesis of MS as a chronic autoimmune and inflammatory disease. First, we describe the main cells involved in MS pathogenesis, both from neural tissue and from the immune system, and including a new participant, the adipocyte, focusing on their roles in MS. Second, we concentrate on the role of several adipokines that are able to participate in the mediation of the immune response in MS and on the possible cross talk between the latter. Finally, we explore recent therapy that involves the transplantation of adipocyte precursor cells for the treatment of MS.

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