Abstract
Abstract Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). Chronic infection with the gammaherpesvirus Epstein Barr virus (EBV) is the leading environmental risk factor, and the mechanisms behind this risk, including the role of host genetics, are still unclear. We have previously shown that host genetics play an essential role in the infection outcomes of a rodent pathogen homologous to EBV, murine gammaherpesvirus 68 (MHV68), where poor control of MHV-68 replication was associated with an expansion of cytotoxic CX3CR1+KLRG1+ T helper cells (ThCTL). To explore how genetically-determined infection outcomes modulate CNS autoimmunity, C57BL/6J (B6) and 129S1/SvImJ (129S) mice were first chronically infected with MHV-68 and then immunized for induction of experimental autoimmune encephalomyelitis (EAE), a rodent model of MS. Viral load was higher in 129S mice, and EAE clinical scores were more exacerbated by MHV-68 infection compared with B6. MHV-68 infection induced higher levels of CD8 T cells and IFNg production in CNS in both strains. In contrast, MHV-68 infection only promoted ThCTL infiltration into the CNS of B6 mice. Ongoing experiments will address the functional role of CD8 T cells and ThCTL. Because poor control of EBV and enhanced anti-EBV responses are associated with greater MS risk, our findings suggest that this could result from genetically determined control of viral load and augmented ThCTL and/or CD8 T cell responses in the CNS.
Published Version
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