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 (gamma HV-68), the murine homolog to EBV, to examine how infection by a virus like EBV could enhance CNS autoimmunity. Mice latently infected with gamma HV-68 developed more severe EAE including heightened paralysis and mortality. Similar to MS, gamma HV-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 gamma HV-68 EAE mice were primarily Th1, producing heightened levels of IFN-gamma and T-bet accompanied by IL-17 suppression, whereas a Th17 response was observed in uninfected EAE mice. Clearly, gamma HV-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.
Gammaherpesvirus Latency Accentuates EAE Pathogenesis: Relevance to Epstein-Barr Virus and Multiple Sclerosis / Costanza Casiraghi;Iryna Shanina;Sehyun Cho;Michael L. Freeman;Marcia A. Blackman;Marc S. Horwitz. - In: PLOS PATHOGENS. - ISSN 1553-7374. - ELETTRONICO. - 8:(2012), pp. e1002715.1-e1002715.16. [10.1371/journal.ppat.1002715]
Gammaherpesvirus Latency Accentuates EAE Pathogenesis: Relevance to Epstein-Barr Virus and Multiple Sclerosis
CASIRAGHI, COSTANZA;
2012
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 (gamma HV-68), the murine homolog to EBV, to examine how infection by a virus like EBV could enhance CNS autoimmunity. Mice latently infected with gamma HV-68 developed more severe EAE including heightened paralysis and mortality. Similar to MS, gamma HV-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 gamma HV-68 EAE mice were primarily Th1, producing heightened levels of IFN-gamma and T-bet accompanied by IL-17 suppression, whereas a Th17 response was observed in uninfected EAE mice. Clearly, gamma HV-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.File | Dimensione | Formato | |
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ppat.1002715.s001.tif
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Descrizione: Figure S1: γHV-68 EAE mice show increased amount of immune cells infiltrations in the spinal cords.
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Descrizione: Figure S2: γHV-68 EAE mice show increased T cell expression of IFN-γ accompanied by IL-17 suppression after MOG restimulation.
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Descrizione: Figure S3: γHV-68 EAE mice show increased levels of pro-inflammatory cytokines in the serum.
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ppat.1002715.s004.tif
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Descrizione: Figure S4: γHV-68 EAE mice show increased levels of IFN-γ in CNS supernatants
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ppat.1002715.s005.tif
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Descrizione: Figure S5: γHV-68 EAE mice show increased levels of CXCR3 on splenic T cells.
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