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 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 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 The Interaction between Viral and Environmental Risk Factors in the Pathogenesis of Multiple Sclerosis

2019 ◽  
Vol 20 (2) ◽  
pp. 303 ◽  
Author(s):  
Rachael Tarlinton ◽  
Timur Khaibullin ◽  
Evgenii Granatov ◽  
Ekaterina Martynova ◽  
Albert Rizvanov ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Large Scale ◽  
Motor Impairment ◽  
Endogenous Retrovirus ◽  
Barr Virus ◽  
Scale Population ◽  
Epidemiological Risk ◽  
The Central Nervous System ◽  
Epstein Barr

Multiple sclerosis (MS) is a chronic debilitating inflammatory disease of unknown ethology targeting the central nervous system (CNS). MS has a polysymptomatic onset and is usually first diagnosed between the ages of 20–40 years. The pathology of the disease is characterized by immune mediated demyelination in the CNS. Although there is no clinical finding unique to MS, characteristic symptoms include sensory symptoms visual and motor impairment. No definitive trigger for the development of MS has been identified but large-scale population studies have described several epidemiological risk factors for the disease. This list is a confusing one including latitude, vitamin D (vitD) levels, genetics, infection with Epstein Barr Virus (EBV) and endogenous retrovirus (ERV) reactivation. This review will look at the evidence for each of these and the potential links between these disparate risk factors and the known molecular disease pathogenesis to describe potential hypotheses for the triggering of MS pathology.

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 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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