Epstein–Barr Virus Infection and Multiple Sclerosis: A Review

Ascherio, Alberto; Munger, Kassandra L.

doi:10.1007/s11481-010-9201-3

Cited by 230 publications

(197 citation statements)

References 73 publications

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“…This could be caused by an infectious organism located in the adjacent meninges or by a chronic compartmentalised inflammatory response to selfantigen(s). Several epidemiological studies have suggested that Epstein-Barr virus (EBV) is one of the strongest candidates for this infectious agent [56][57][58] and EBV proteins and RNA have been detected in B-cells in the meninges and perivascular spaces of MS cases with extensive meningeal infiltrates and cortical demyelination [59][60][61] . It has been proposed that failure to control latent EBV infection in an immune privileged site, such as the subarachnoid space, could lead to recurrent intrathecal reactivation of EBV and tissue damage in the nearby grey matter 62,63 .…”

Section: Inflammatory Grey Matter Damagementioning

confidence: 99%

Exploring the origins of grey matter damage in multiple sclerosis

et al. 2015

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Multiple sclerosis is characterized at the gross pathological level by the presence of widespread focal demyelinating lesions of the myelin-rich white matter. However, it is becoming clear that grey matter is not spared, even during the earliest phases of the disease. Furthermore, grey matter damage may have an important role both in physical and cognitive disability. Grey matter pathology involves both inflammatory and neurodegenerative mechanisms, but the relationship between the two is unclear. Histological, immunological and neuroimaging studies have provided new insight in this rapidly expanding field, and form the basis of the most recent hypotheses on the pathogenesis of grey matter damage. DOI: https://doi.org/10.1038/nrn3900Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-111099 Accepted Version Originally published at: Calabrese, Massimiliano; Magliozzi, Roberta; Ciccarelli, Olga; Geurts, Jeroen J G; Reynolds, Richard; Martin, Roland (2015). Exploring the origins of grey matter damage in multiple sclerosis. Nature Reviews Neuroscience, 16 (3) AbstractMultiple sclerosis is characterised at the gross pathological level by the presence of widespread focal demyelinating lesions of the myelin-rich white matter. However, in recent years it has become clear that grey matter is not spared, even during the earliest phases of the disease. Furthermore, grey matter damage has been suggested to have an important role both in physical and cognitive disability. Grey matter pathology involves both inflammatory and neurodegenerative mechanisms, but the relationship between the two is unclear. This review will summarize and highlight important histological, immunological, and neuroimaging results from this rapidly expanding field and will address the most recent hypotheses on the pathogenesis of grey matter damage.

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Section: Inflammatory Grey Matter Damagementioning

confidence: 99%

Exploring the origins of grey matter damage in multiple sclerosis

et al. 2015

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“…With these studies as a basis, there are many further questions to address. How might EBV infection, particularly a history of IM, predispose both to an autoimmune disease, multiple sclerosis [95] and to Hodgkin Lymphoma [96]? Might an inflammatory environment, particularly that induced by a high EBV load in IM, allow rogue T cell priming, leading in one case to cross-reactive auto-immune recognition of neuronal cells and in the other to wrongly polarized T cells that nurture rather than deter lymphoma growth?…”

Section: Conclusion and Future Challengesmentioning

confidence: 99%

Cellular immune controls over Epstein–Barr virus infection: new lessons from the clinic and the laboratory

Rickinson

Long

Palendira

et al. 2014

Trends in Immunology

110

104

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Epstein-Barr virus (EBV), a human herpesvirus with potent B cell growth transforming ability, induces multiple cellular immune responses in the infected host. How these host responses work together to prevent virus pathogenicity, and how immune imbalance predisposes to disease, remain poorly understood. Here, we describe three ongoing lines of enquiry that are shedding new light on these issues. These focus on: (i) patients with infectious mononucleosis or its fatal equivalent, X-linked lymphoproliferative disease; (ii) EBV infection in a range of new, genetically defined, primary immune deficiency states; and (iii) experimental infection in two complementary animal models, the rhesus macaque and the human haemopoietic stem cell reconstituted mouse.

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“…6 Compared with controls, MS patients often show elevated levels of antibody reactivity against EBVrelated antigens such as viral capsid antigen, Epstein Barr nuclear antigen 1 (EBNA1) 7,8 and several EBNA1 domains, in particular the 385-420 amino-acid domain. 9 The aim of this study was to investigate the interaction of reported IM and antibody titres toward EBV antigens with HLA-DRB1*15 and A*02 in a large populationbased case-control study comprising newly diagnosed MS cases in Sweden.…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr virus and multiple sclerosis: interaction with HLA

et al. 2011

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Epstein-Barr virus (EBV) infection, history of infectious mononucleosis (IM)and HLA-A and DRB1 have all been proposed as risk factors for multiple sclerosis (MS). Our aim was to analyse possible interactions between antibodies against Epstein-Barr virus nuclear antigen 1 (EBNA1) or EBNA1 fragments, presence of DRB1*15 and absence of A*02. The study population includes newly diagnosed cases and matched controls. Interaction on the additive scale was calculated using attributable proportion due to interaction (AP), which is the proportion of the incidence among individuals exposed to two interacting factors that is attributable to the interaction per se. IM showed association with MS, odds ratio (OR) ¼ 1.89 (1.45-2.48% confidence interval (CI)), as did raised EBNA1 IgG OR ¼ 1.74 (1.38-2.18 95%CI). All EBNA1 fragment IgGs were associated with MS risk. However, EBNA1 fragment 385-420 IgG levels were more strongly associated to MS than total EBNA1 IgG, OR ¼ 3.60 (2.75-4.72 95%CI), and also interacted with both DRB1*15 and absence of A*02, AP 0.60 (0.45-0.76 95%CI) and AP 0.39 (0.18-0.61 95%CI), respectively. The observed interaction between HLA class I and II genotype and reactivity to EBV-related epitopes suggest that the mechanism through which HLA genes influence the risk of MS may, at least in part, involve the immune control of EBV infection.

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Epstein–Barr Virus Infection and Multiple Sclerosis: A Review

Cited by 230 publications

References 73 publications

Exploring the origins of grey matter damage in multiple sclerosis

Exploring the origins of grey matter damage in multiple sclerosis

Cellular immune controls over Epstein–Barr virus infection: new lessons from the clinic and the laboratory

Epstein-Barr virus and multiple sclerosis: interaction with HLA

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