Infection with murine gamma herpesvirus 68 modifies experimental autoimmune encephalomyelitis (101.1)

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Abstract Recent findings have identified Epstein-Barr virus (EBV) as a putative environmental trigger of multiple sclerosis (MS) but the mechanisms by which this virus causes MS remains elusive. We used murine gamma herpesvirus 68 (MγHV), the murine homolog to EBV, to examine how MγHV infection could aid in the enhancement of an autoimmune reaction against the CNS. C57Bl/6 mice were infected with MγHV and five weeks later, when the virus is cleared and has established latency, EAE was induced. Mice previously infected with MγHV developed a more severe EAE course showing both signs of paralysis and other neurological symptoms such as ataxia. MγHV EAE mice had higher levels of IFN-γ and TNF-α in the serum when compared to EAE mice and showed pronounced CD4 and CD8 T cell infiltrations both in the spinal cord and the brain parenchyma. On the other hand, CD4 T cells were less prominent in the brain parenchyma of uninfected EAE mice and CD8 T cells were absent. CD4 and CD8 T cells isolated from the CNS of MγHV EAE mice produced higher levels of IFN-γ accompanied by IL-17 suppression, whereas CD4 T cells isolated from the CNS of EAE mice produced high levels of IL-17 and lower IFN-γ levels. The absence of IL-17 production in infected mice suggests that the disease might be triggered by different T cell subsets than typical EAE. In conclusion, the ability of MγHV to elicit a more pathogenic T cell response could represent a new mechanism through which EBV triggers autoimmunity.