Epstein–Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies

Bar‐Or, Amit; Pender, Michael P.; Khanna, Rajiv; Steinman, Lawrence; Hartung, Hans‐Peter; Maniar, Tap; Croze, Ed; Aftab, Blake T.; Giovannoni, Gavin; Joshi, Manher

doi:10.1016/j.molmed.2019.11.003

Cited by 188 publications

(156 citation statements)

References 113 publications

(154 reference statements)

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“…Epstein-Barr virus is one of the most thoroughly investigated pathogens regarding T-cell responses in MS. Many theories have been proposed how EBV can influence MS pathogenesis (9). One hypothesis is that, due to the chronic nature of this infection, continuous antigen presentation by B cells leads to functionally impaired, so-called "exhausted" T cells (8,22).…”

Section: Impaired T Cell-mediated Control Of Pathogenic B Cells In Msmentioning

confidence: 99%

“…Besides for HLA-DRB1 * 1501, other genetic risk variants that have been identified in the past decades also appear to potentiate B and Th cell activation, a feature that is shared amongst several autoimmune disorders (7). Furthermore, infectious triggers such as the Epstein-Barr virus (EBV) alter their function and reactivity in MS (5,6,8,9). The current view is that transmigration of lymphocyte subsets into the CNS signifies relapsing disease, while compartmentalized CNS inflammation, as seen during disease progression, seems to be driven by tissue-resident populations (10,11).…”

Section: Introductionmentioning

confidence: 99%

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B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers

et al. 2020

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Historically, multiple sclerosis (MS) has been viewed as being primarily driven by T cells. However, the effective use of anti-CD20 treatment now also reveals an important role for B cells in MS patients. The results from this treatment put forward T-cell activation rather than antibody production by B cells as a driving force behind MS. The main question of how their interaction provokes both B and T cells to infiltrate the CNS and cause local pathology remains to be answered. In this review, we highlight key pathogenic events involving B and T cells that most likely contribute to the pathogenesis of MS. These include (1) peripheral escape of B cells from T cell-mediated control, (2) interaction of pathogenic B and T cells in secondary lymph nodes, and (3) reactivation of B and T cells accumulating in the CNS. We will focus on the functional programs of CNS-infiltrating lymphocyte subsets in MS patients and discuss how these are defined by mechanisms such as antigen presentation, co-stimulation and cytokine production in the periphery. Furthermore, the potential impact of genetic variants and viral triggers on candidate subsets will be debated in the context of MS.

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Section: Impaired T Cell-mediated Control Of Pathogenic B Cells In Msmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers

et al. 2020

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“…Viral infection contributes to demyelination through several mechanisms such as molecular mimicry, bystander inflammatory damage or direct oligodendrocyte infection [39]. MS onset may occur long after acute infection as consistently demonstrated for by Epstein-Barr virus (EBV) [40]. Infectious mononucleosis by EBV supervening during the early adulthood, in fact, is an established risk factor for further MS development [41][42][43][44][45]; moreover, compelling evidence shows that almost all subjects with MS have positive serology for EBV.…”

Section: Multiple Sclerosismentioning

confidence: 99%

COVID-19: dealing with a potential risk factor for chronic neurological disorders

Schirinzi

Landi²,

Liguori

2020

J Neurol

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SARS-CoV2 infection is responsible for a complex clinical syndrome, named Coronavirus Disease 2019 (COVID-19), whose main consequences are severe pneumonia and acute respiratory distress syndrome. Occurrence of acute and subacute neurological manifestations (encephalitis, stroke, headache, seizures, Guillain-Barrè syndrome) is increasingly reported in patients with COVID-19. Moreover, SARS-CoV2 immunopathology and tissue colonization in the gut and the central nervous system, and the systemic inflammatory response during COVID-19 may potentially trigger chronic autoimmune and neurodegenerative disorders. Specifically, Parkinson's disease, multiple sclerosis and narcolepsy present several pathogenic mechanisms that can be hypothetically initiated by SARS-CoV2 infection in susceptible individuals. In this short narrative review, we summarize the clinical evidence supporting the rationale for investigating SARS-CoV2 infection as risk factor for these neurological disorders, and suggest the opportunity to perform in the future SARS-CoV2 serology when diagnosing these disorders.

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“…MS is a systemic autoimmune disease characterized by demyelinization in the central nervous system, and strong epidemiological evidence indicates that EBV infection is almost a prerequisite for its development [91]. Monoclonal antibodies (MAbs) specific to the B-cell marker CD20 were shown to have a pronounced therapeutic effect in MS, indicating a critical role for B cells in its pathogenesis.…”

Section: Multiple Sclerosismentioning

confidence: 99%

Animal Models for Gammaherpesvirus Infections: Recent Development in the Analysis of Virus-Induced Pathogenesis

Fujiwara

Nakamura

2020

Pathogens

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Epstein–Barr virus (EBV) is involved in the pathogenesis of various lymphomas and carcinomas, whereas Kaposi’s sarcoma-associated herpesvirus (KSHV) participates in the pathogenesis of endothelial sarcoma and lymphomas. EBV and KSHV are responsible for 120,000 and 44,000 annual new cases of cancer, respectively. Despite this clinical importance, no chemotherapies or vaccines have been developed for virus-specific treatment and prevention of these viruses. Humans are the only natural host for both EBV and KSHV, and only a limited species of laboratory animals are susceptible to their experimental infection; this strict host tropism has hampered the development of their animal models and thereby impeded the study of therapeutic and prophylactic strategies. To overcome this difficulty, three main approaches have been used to develop animal models for human gammaherpesvirus infections. The first is experimental infection of laboratory animals with EBV or KSHV. New-world non-human primates (NHPs) and rabbits have been mainly used in this approach. The second is experimental infection of laboratory animals with their own inherent gammaherpesviruses. NHPs and mice have been mainly used here. The third, a recent trend, employs experimental infection of EBV or KSHV or both to immunodeficient mice reconstituted with human immune system components (humanized mice). This review will discuss how these three approaches have been used to reproduce human clinical conditions associated with gammaherpesviruses and to analyze the mechanisms of their pathogenesis.

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Epstein–Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies

Cited by 188 publications

References 113 publications

B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers

B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers

COVID-19: dealing with a potential risk factor for chronic neurological disorders

Animal Models for Gammaherpesvirus Infections: Recent Development in the Analysis of Virus-Induced Pathogenesis

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