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

2020 ◽  
Vol 217 ◽  
pp. 15-24 ◽  
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

scholarly journals Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk

2019 ◽  
Vol 116 (34) ◽  
pp. 16955-16960 ◽  
Author(s):  
Katarina Tengvall ◽  
Jesse Huang ◽  
Cecilia Hellström ◽  
Patrick Kammer ◽  
Martin Biström ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Molecular Mimicry ◽  
Nuclear Antigen ◽  
Immune Reactivity ◽  
Barr Virus ◽  
Epstein Barr ◽  
Antibody Levels

Multiple sclerosis (MS) is a chronic inflammatory, likely autoimmune disease of the central nervous system with a combination of genetic and environmental risk factors, among which Epstein-Barr virus (EBV) infection is a strong suspect. We have previously identified increased autoantibody levels toward the chloride-channel protein Anoctamin 2 (ANO2) in MS. Here, IgG antibody reactivity toward ANO2 and EBV nuclear antigen 1 (EBNA1) was measured using bead-based multiplex serology in plasma samples from 8,746 MS cases and 7,228 controls. We detected increased anti-ANO2 antibody levels in MS (P = 3.5 × 10−36) with 14.6% of cases and 7.8% of controls being ANO2 seropositive (odds ratio [OR] = 1.6; 95% confidence intervals [95%CI]: 1.5 to 1.8). The MS risk increase in ANO2-seropositive individuals was dramatic when also exposed to 3 known risk factors for MS: HLA-DRB1*15:01 carriage, absence of HLA-A*02:01, and high anti-EBNA1 antibody levels (OR = 24.9; 95%CI: 17.9 to 34.8). Reciprocal blocking experiments with ANO2 and EBNA1 peptides demonstrated antibody cross-reactivity, mapping to ANO2 [aa 140 to 149] and EBNA1 [aa 431 to 440]. HLA gene region was associated with anti-ANO2 antibody levels and HLA-DRB1*04:01 haplotype was negatively associated with ANO2 seropositivity (OR = 0.6; 95%CI: 0.5 to 0.7). Anti-ANO2 antibody levels were not increased in patients from 3 other inflammatory disease cohorts. The HLA influence and the fact that specific IgG production usually needs T cell help provides indirect evidence for a T cell ANO2 autoreactivity in MS. We propose a hypothesis where immune reactivity toward EBNA1 through molecular mimicry with ANO2 contributes to the etiopathogenesis of MS.

scholarly journals Epstein-Barr Virus Transactivates the Human Endogenous Retrovirus HERV-K18 that Encodes a Superantigen

Immunity ◽  
2001 ◽  
Vol 15 (4) ◽  
pp. 579-589 ◽  
Author(s):  
Natalie Sutkowski ◽  
Bernard Conrad ◽  
David A Thorley-Lawson ◽  
Brigitte T Huber
Keyword(s):  
Epstein Barr Virus ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Human endogenous retrovirus-K18 Env as a risk factor in multiple sclerosis

2008 ◽  
Vol 14 (9) ◽  
pp. 1175-1180 ◽  
Author(s):  
AK Tai ◽  
EJ O’Reilly ◽  
KA Alroy ◽  
KC Simon ◽  
KL Munger ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Risk Factor ◽  
Statistical Significance ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Barr Virus ◽  
Relative Risks ◽  
Increased Risk ◽  
Epstein Barr ◽  
Nested Case Control

Background The human endogenous retrovirus (HERV)-K18 Env is an Epstein-Barr virus (EBV)-associated superantigen. Given the evidence for a role of EBV in the etiology of multiple sclerosis (MS), HERV-K18 Env is a plausible candidate for association with MS. Objective To assess whether variation in HERV-K18 Env is a risk factor for MS. Methods We developed a single nucleotide polymorphism-based genotyping method to determine the distribution of the three alleles of HERV-K18 env. We then conducted a nested case-control study including 207 MS cases and 403 matched controls. Analyses were replicated in an independent series of 909 MS cases and 339 controls. Results Overall, there was a significant association between HERV-K18 env genotype and MS risk (χ2 P = 0.03). As compared with K18.2/K18.2 individuals, risk of MS was three fold higher among K18.3/K18.3 individuals ( P = 0.03). An increase in MS risk among carriers of the K18.3 allele was also observed in the replication study, but did not reach statistical significance. In pooled analyses, K18.3/K18.3 individuals had a significantly increased risk of MS (relative risks [RR] comparing K18.3/K18.3 vs K18.2/K18.2 = 2.7; 95% confidence interval: 1.1–6.4). Conclusion Variation in EBV-associated superantigen HERV-K18 Env could influence the genetic susceptibility to MS.

scholarly journals The role of infections in multiple sclerosis

2019 ◽  
Vol 25 (7) ◽  
pp. 891-901 ◽  
Author(s):  
Mariano Marrodan ◽  
Lucas Alessandro ◽  
Mauricio F Farez ◽  
Jorge Correale
Keyword(s):  
Multiple Sclerosis ◽  
Chlamydia Pneumoniae ◽  
Treatment Strategies ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Barr Virus ◽  
Microbial Infections ◽  
Epstein Barr ◽  
New Treatment ◽  
Tract Infections

Several lines of evidence suggest that multiple sclerosis (MS), like other autoimmune diseases, may be triggered by microbial infections. Pathogens associated with development or exacerbation of MS include bacteria, such as Chlamydia pneumoniae, Staphylococcus aureus-produced enterotoxins that function as superantigens, and viruses of the Herpesviridae (Epstein–Barr virus and human herpes virus 6) and human endogenous retrovirus families. However, to date, no single pathogen has been accepted as causal agent. In addition, common upper respiratory, gastrointestinal, and urogenital tract infections have also been associated with MS exacerbations. Although evidence of an infectious etiology as cause of MS in humans remains inconclusive, microbial agents may modulate the neuroimmunological system of genetically susceptible individuals. Decoding the epidemiological contribution of different microorganisms to MS, along with their pathogenic mechanisms, may help develop new treatment strategies and prevent relapses.

scholarly journals Anti-Human Herpesvirus 6 A/B Antibodies Titers Correlate With Multiple Sclerosis-Associated Retrovirus Envelope Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Silvia Pérez-Pérez ◽  
María I. Domínguez-Mozo ◽  
M. Ángel García-Martínez ◽  
M. Celeste García-Frontini ◽  
Noelia Villarrubia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Human Herpesvirus ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Expression Levels ◽  
Barr Virus ◽  
Healthy Donors ◽  
Epstein Barr ◽  
Gene Expression Levels

Human endogenous retrovirus W family envelope proteins (pHERV-W ENV/syncytin-1) have been repeatedly associated with multiple sclerosis (MS). Here, we have focused on the study of pHERV-W ENV/syncytin-1 expression levels in MS patients (relapsing and progressive forms) and in healthy donors (HD) and on exploring their possible relationship with Epstein-Barr virus (EBV) and human herpesvirus-6A/B (HHV-6A/B). We included blood samples from 101 MS patients and 37 HD to analyze antiviral antibody titers by ELISA and pHERV-W ENV/syncytin-1 expression levels by flow cytometry as well as by qPCR. Patients with relapsing MS forms showed significantly higher pHERV-W ENV/syncytin-1 protein and gene expression levels than HD. Progressive MS patients also showed significantly higher protein and gene expression levels than both HD and relapsing MS patients. Regarding antiviral antibodies titers, anti-HHV-6A/B IgM levels were positively correlated with pHERV-W ENV/syncytin-1 protein expression levels in patients with relapsing MS, while in the progressive forms patients this correlation was found with anti-HHVA/B IgG levels. Therefore, pHERV-W ENV could be involved in MS pathogenesis, playing a role in relapsing and progressive forms. Besides, anti-HHV-6A/B antibodies positively correlated with pHERV-W ENV expression. Further studies are needed to better understand this possible relationship.

scholarly journals Epstein-Barr Virus Latent Membrane Protein LMP-2A Is Sufficient for Transactivation of the Human Endogenous Retrovirus HERV-K18 Superantigen

2004 ◽  
Vol 78 (14) ◽  
pp. 7852-7860 ◽  
Author(s):  
Natalie Sutkowski ◽  
Gang Chen ◽  
German Calderon ◽  
Brigitte T. Huber
Keyword(s):  
T Cells ◽  
Membrane Protein ◽  
Epstein Barr Virus ◽  
Endogenous Retrovirus ◽  
Latent Membrane Protein ◽  
Human Endogenous Retrovirus ◽  
Barr Virus ◽  
Epstein Barr ◽  
Virus Latent Membrane Protein

ABSTRACT Superantigens are microbial proteins that strongly stimulate T cells. We described previously that the Epstein-Barr virus (EBV) transactivates a superantigen encoded by the human endogenous retrovirus, HERV-K18. We now report that the transactivation is dependent upon the EBV latent cycle proteins. Moreover, LMP-2A is sufficient for induction of HERV-K18 superantigen activity.

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