| Association of innate immune activation with latent Epstein-Barr virus in active MS lesions. | |
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MedLine Citation:
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PMID: 22156987 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE:To determine whether the activation of innate immune responses, which can be elicited by pathogenic and endogenous triggers, is associated with the presence of Epstein-Barr virus (EBV) infection in the multiple sclerosis (MS) brain. METHODS:White matter postmortem MS (n = 10) and control tissue (n = 11) was analyzed for the expression of the proinflammatory cytokine interferon α (IFNα) by immunohistochemistry and for EBV by using the highly sensitive method of EBV-encoded RNA (EBER) in situ hybridization. RESULTS:We detected overexpression of IFNα in active areas of white matter MS lesions but not in inactive MS lesions, normal-appearing white matter, or normal brains. The presence of IFNα in macrophages and microglia (expressing human leukocyte antigen class II) is suggestive of local production as part of an acute inflammatory process. Interestingly, EBERs were also specifically detected in areas where IFNα was overexpressed in these preselected active MS lesions. EBER+ cells were also found in CNS lymphoma and stroke cases, but were absent in other control brains. We next addressed a potential mechanism, e.g., the role of EBERs in eliciting IFNα production, and transfected EBERs into human embryonic kidney (HEK) cells. We used HEK cells that stably expressed Toll-like receptor-3, which recognizes double-stranded RNAs, associated with many viral infections. EBERs elicited IFNα production in vitro. CONCLUSION:These findings suggest that latent EBV infection may contribute to the inflammatory milieu in active MS lesions by activating innate immune responses, e.g., IFNα production. Unraveling the underlying mechanisms may help in uncovering causal pathways and developing better treatment strategies for MS and other neuroinflammatory diseases. |
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Authors:
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J S Tzartos; G Khan; A Vossenkamper; M Cruz-Sadaba; S Lonardi; E Sefia; A Meager; A Elia; J M Middeldorp; M Clemens; P J Farrell; G Giovannoni; U-C Meier |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-7 |
Journal Detail:
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Title: Neurology Volume: - ISSN: 1526-632X ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0401060 Medline TA: Neurology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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From the Department of Neuropathology (J.S.T.), John Radcliffe Hospital, University of Oxford, UK; Department of Biochemistry (J.S.T.), Hellenic Pasteur Institute, Athens, Greece; Faculty of Medicine and Health Sciences (G.K.), Department of Microbiology and Immunology, United Arab Emirates University, Al-Ain, UAE; Institute of Cell and Molecular Sciences, Neuroimmunology Group, Neuroscience Centre (U.C.M., G.G., E.S.), and Centre for Infectious Disease (A.V.), Queen Mary University of London, UK; Biotherapeutics (A.M.), National Institute for Biological Standards and Control, Health Protection Agency, South Mimms, Potters Bar, UK; St George's (A.E.), University of London, Basic Medical Sciences, of London, UK; Department of Biochemistry (J.S.T.), Hellenic Pasteur Institute, Athens, Greece; VU University Medical Centre (J.M.), Amsterdam, the Netherlands; Department of Chemistry & Biochemistry (M.C.), School of Life Sciences, University of Sussex, Brighton, UK; Section of Virology (P.F.), Imperial College Faculty of Medicine, London, UK; Department of Surgical Pathology (S.L.), University of Brescia, Italy; and Instituto de Medicina Molecular Aplicada (M.C.S.), University San Pablo, Madrid, Spain. |
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