Abstract
Epstein-Barr virus (EBV) has been identified as a putative environmental trigger of multiple sclerosis (MS), yet EBV's role in MS remains elusive. We utilized murine gamma herpesvirus 68 (γHV-68), the murine homolog to EBV, to examine how infection by a virus like EBV could enhance CNS autoimmunity. Mice latently infected with γHV-68 developed more severe EAE including heightened paralysis and mortality. Similar to MS, γHV-68EAE mice developed lesions composed of CD4 and CD8 T cells, macrophages and loss of myelin in the brain and spinal cord. Further, T cells from the CNS of γHV-68 EAE mice were primarily Th1, producing heightened levels of IFN-γ and T-bet accompanied by IL-17 suppression, whereas a Th17 response was observed in uninfected EAE mice. Clearly, γHV-68 latency polarizes the adaptive immune response, directs a heightened CNS pathology following EAE induction reminiscent of human MS and portrays a novel mechanism by which EBV likely influences MS and other autoimmune diseases.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain / immunology*
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Brain / pathology
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Brain / virology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / virology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / virology
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Cells, Cultured
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Encephalomyelitis, Autoimmune, Experimental / virology*
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Herpesviridae Infections / immunology
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Herpesviridae Infections / pathology
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Herpesvirus 4, Human / pathogenicity
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Interferon-gamma / biosynthesis
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Interleukin-17 / biosynthesis
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Macrophages / immunology
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Macrophages / virology
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Mice
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Mice, Inbred C57BL
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Multiple Sclerosis / immunology
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Multiple Sclerosis / virology
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Rhadinovirus / pathogenicity*
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Spinal Cord / immunology*
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Spinal Cord / pathology
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Spinal Cord / virology
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T-Box Domain Proteins / biosynthesis
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Th1 Cells / immunology
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Th17 Cells / immunology
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Virus Latency*
Substances
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Interleukin-17
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Interferon-gamma