What are T-cells telling us about how EBV causes MS?

Giovannoni, Gavin; Hawkes, Christopher H.; Lechner‐Scott, Jeannette; Lévy, Michaël; Yeh, E. Ann

doi:10.1016/j.msard.2022.104434

Cited by 3 publications

(3 citation statements)

References 27 publications

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“…Please note that if EBV is triggering MS disease activity in the CNS, then CNS-penetrant antivirals or EBV immunotherapies will be required. This figure has been adapted from a previous figure in an MSARD editorial commentary [6]. CAR, chimeric antigen receptors; CNS, central nervous system; EBV, Epstein--Barr virus; MS, multiple sclerosis.…”

Section: Immunology and Virology Of Epstein-barr Virus In Multiple Sc...mentioning

confidence: 99%

“…Current hypotheses include molecular mimicry, immune dysregulation, active EBV infection, and the activation of human endogenous retroviruses (HERVs). Whether EBV triggers MS and then does not play a further role in disease pathogenesis (hit-and-run hypothesis) or is causing the disease process via active infection (the driver hypothesis) is unknown [6]. In addition, the pathogenic site of EBV latent-lytic cycling is unknown (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Targeting Epstein–Barr virus in multiple sclerosis: when and how?

Giovannoni

2024

Current Opinion in Neurology

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Purpose of review Epidemiological evidence implicates Epstein–Barr virus (EBV) as the cause of multiple sclerosis (MS). However, its biological role in the pathogenesis of MS is uncertain. The article provides an overview of the role of EBV in the pathogenesis of MS and makes a case for targeting EBV as a treatment strategy for MS. Recent findings EBV potentially triggers autoimmunity via molecular mimicry or immune dysregulation. Another hypothesis, supported by immunological and virological data, indicates that active EBV infection via latent-lytic infection cycling within the central nervous system or periphery drives MS disease activity. This supports testing small molecule anti-EBV agents targeting both latent and lytic infection, central nervous system-penetrant B-cell therapies and EBV-targeted immunotherapies in MS. Immunotherapies may include EBV-specific cytotoxic or chimeric antigen receptors T-cells, therapeutic EBV vaccines and immune reconstitution therapies to boost endogenous EBV-targeted cytotoxic T-cell responses. Summary EBV is the probable cause of MS and is likely to be driving MS disease activity via latent-lytic infection cycling. There is evidence that all licensed MS disease-modifying therapies target EBV, and there is a compelling case for testing other anti-EBV strategies as potential treatments for MS.

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Section: Immunology and Virology Of Epstein-barr Virus In Multiple Sc...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeting Epstein–Barr virus in multiple sclerosis: when and how?

Giovannoni

2024

Current Opinion in Neurology

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“…In this study, only one out of 955 MS patients was likely to be not immune to EBV. It has been suggested that high levels of serum anti-EBNA1 IgG may reflect a defective control of EBV infection [ 43 , 44 ].…”

Section: Latency Proteinsmentioning

confidence: 99%

Markers of Epstein-Barr Virus Infection in Patients with Multiple Sclerosis

2023

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Viral infections have been suspected of being involved in the pathogenesis of certain autoimmune diseases for many years. Epstein-Barr virus (EBV), a DNA virus belonging to the Herpesviridae family, is thought to be associated with the onset and/or the progression of multiple sclerosis (MS), systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome and type 1 diabetes. The lifecycle of EBV consists of lytic cycles and latency programmes (0, I, II and III) occurring in infected B-cells. During this lifecycle, viral proteins and miRNAs are produced. This review provides an overview of the detection of EBV infection, focusing on markers of latency and lytic phases in MS. In MS patients, the presence of latency proteins and antibodies has been associated with lesions and dysfunctions of the central nervous system (CNS). In addition, miRNAs, expressed during lytic and latency phases, may be detected in the CNS of MS patients. Lytic reactivations of EBV can occur in the CNS of patients as well, with the presence of lytic proteins and T-cells reacting to this protein in the CNS of MS patients. In conclusion, markers of EBV infection can be found in MS patients, which argues in favour of a relationship between EBV and MS.

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