title: Gammaherpesvirus latency accentuates EAE pathogenesis: relevance to Epstein-Barr virus and multiple sclerosis.
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.
authors.affiliation: Department of Microbiology and Immunology, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Costanza
authors.initials: C
authors.lastname: Casiraghi
authors.forename: Iryna
authors.initials: I
authors.lastname: Shanina
authors.forename: Sehyun
authors.initials: S
authors.lastname: Cho
authors.forename: Michael L
authors.initials: ML
authors.lastname: Freeman
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Blackman
authors.forename: Marc S
authors.initials: MS
authors.lastname: Horwitz
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D006566:Herpesviridae Infections / Q000276:immunology / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology / Q000821:virology; D018144:Rhadinovirus / Q000472:pathogenicity*; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology / Q000821:virology; D020825:T-Box Domain Proteins / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D017735:Virus Latency; D000098815:T-bet Transcription Factor
chemical_list: D020381:Interleukin-17; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma