Impact of Epstein-Barr Virus Nuclear Antigen 1 on Neuroinflammation in PARK2 Knockout Mice.

This study aimed to explore the intricate relationship between mitochondrial dysfunction, infection, and neuroinflammation, focusing specifically on the impact of pathogenic epitopes of the Epstein-Barr Virus (EBV) nuclear antigen 1 (EBNA1) in a mouse model of mitochondrial dysfunctions. The investigation included female middle-aged PARK2(-/-) and C57BL/6J wild-type mice immunized with EBNA1(386-405) or with active experimental autoimmune encephalomyelitis (EAE) induction by the myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide. The PARK2(-/-) mice developed more severe EAE than the wild-type mice. Following immunization with EBNA1(386-405), only PARK2(-/-) exhibited symptoms resembling EAE. During the acute phase, PARK2(-/-) mice immunized with either MOG(35-55) or EBNA1(386-405) exhibited a similar infiltration of the T cells and macrophages in the spinal cord and decreased glial fibrillary acidic protein (GFAP) expression in the brain. However, the EBNA1(386-405) -immunized PARK2(-/-) mice showed significantly increased frequencies of CD8a(+) T cells and CD11c(+) B cells, and distinct cytokine profiles in the periphery compared to the wild-type controls. These findings highlight the role of EBV in exacerbating inflammation, particularly in the context of mitochondrial deficiencies.