Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen

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.

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Viruses in multiple sclerosis pathogenesis

Access Microbiology ◽

10.1099/acmi.ac2020.po0065 ◽

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.

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Potential molecular mimicry between the human endogenous retrovirus W family envelope proteins and myelin proteins in multiple sclerosis

Immunology Letters ◽

10.1016/j.imlet.2017.02.003 ◽

2017 ◽

Vol 183 ◽

pp. 79-85 ◽

Cited By ~ 9

Author(s):

Ranjan Ramasamy ◽

Blessy Joseph ◽

Trevor Whittall

Keyword(s):

Multiple Sclerosis ◽

Molecular Mimicry ◽

Endogenous Retrovirus ◽

Envelope Proteins ◽

Myelin Proteins ◽

Human Endogenous Retrovirus

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HLA DR2b-binding peptides from human endogenous retrovirus envelope, Epstein-Barr virus and brain proteins in the context of molecular mimicry in multiple sclerosis

Immunology Letters ◽

10.1016/j.imlet.2019.10.017 ◽

2020 ◽

Vol 217 ◽

pp. 15-24 ◽

Cited By ~ 4

Author(s):

Ranjan Ramasamy ◽

Fiyaz Mohammed ◽

Ute-C. Meier

Keyword(s):

Multiple Sclerosis ◽

Epstein Barr Virus ◽

Molecular Mimicry ◽

Endogenous Retrovirus ◽

Human Endogenous Retrovirus ◽

Brain Proteins ◽

Barr Virus ◽

Binding Peptides ◽

Epstein Barr

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Potential Role of Humoral Immunity in the Pathogenesis of Multiple Sclerosis (MS) and Experimental Autoimmune Encephalomyelitis (EAE)

Frontiers in Bioscience ◽

10.2741/2268 ◽

2007 ◽

Vol 12 (1) ◽

pp. 2735 ◽

Cited By ~ 18

Author(s):

Maria del Pilar Martin

Keyword(s):

Multiple Sclerosis ◽

Experimental Autoimmune Encephalomyelitis ◽

Humoral Immunity ◽

Potential Role ◽

Autoimmune Encephalomyelitis ◽

Experimental Autoimmune

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Anti-phospholipid syndrome and COVID-19 thrombosis: connecting the dots

Rheumatology Advances in Practice ◽

10.1093/rap/rkaa081 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Moon Ley Tung ◽

Bryce Tan ◽

Robin Cherian ◽

Bharatendu Chandra

Keyword(s):

Endothelial Dysfunction ◽

Severe Acute Respiratory Syndrome ◽

Potential Role ◽

Molecular Mimicry ◽

Thromboembolic Events ◽

The Past ◽

High Prevalence ◽

Connecting The Dots ◽

Anti Phospholipid Syndrome

Abstract As the coronavirus disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly worldwide, it has emerged as a leading cause of mortality, resulting in >1 million deaths over the past 10 months. The pathophysiology of COVID-19 remains unclear, posing a great challenge to the medical management of patients. Recent studies have reported an unusually high prevalence of thromboembolic events in COVID-19 patients, although the mechanism remains elusive. Several studies have reported the presence of aPLs in COVID-19 patients. We have noticed similarities between COVID-19 and APS, which is an autoimmune prothrombotic disease that is often associated with an infective aetiology. Molecular mimicry and endothelial dysfunction could plausibly explain the mechanism of thrombogenesis in acquired APS. In this review, we discuss the clinicopathological similarities between COVID-19 and APS, and the potential role of therapeutic targets based on the anti-phospholipid model for COVID-19 disease.

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