4165 total record number 127 records this year

Latent virus infection upregulates CD40 expression facilitating enhanced autoimmunity in a model of multiple sclerosis

Casiraghi, C;Mrquez, AC;Shanina, I;Horwitz, MS;

Epstein-Barr virus (EBV) has been identified as a putative environmental trigger of multiple sclerosis (MS) by multiple groups working worldwide. Previously, we reported that when experimental autoimmune encephalomyelitis (EAE) was induced in mice latently infected with murine -herpesvirus 68 (HV-68), the murine homolog to EBV, a disease more reminiscent of MS developed. Specifically, MS-like lesions developed in the brain that included equal numbers of IFN- producing CD4(+) and CD8(+) T cells and demyelination, none of which is observed in MOG induced EAE. Herein, we demonstrate that this enhanced disease was dependent on the HV-68 latent life cycle and was associated with STAT1 and CD40 upregulation on uninfected dendritic cells. Importantly, we also show that, during viral latency, the frequency of regulatory T cells is reduced via a CD40 dependent mechanism and this contributes towards a strong T helper 1 response that resolves in severe EAE disease pathology. Latent -herpesvirus infection established a long-lasting impact that enhances subsequent adaptive autoimmune responses.