Latent murine cytomegalovirus infection contributes to EAE pathogenesis

Abstract

© 2014 University of Kragujevac, Faculty of Science. All rights reserved. Viral infection has been identifi ed as the most likely environmental trigger of multiple sclerosis (MS). Th ere are confl icting data regarding the role of cytomegalovirus (CMV) in MS pathogenesis. We utilised experimental autoimmune encephalomyelitis (EAE)-resistant BALB/c mice and murine cytomegalovirus (MCMV), the murine homolog of CMV, to examine the mechanism by which viral infection enhances autoimmune neuroinfl ammation. Mice subjected to latent neonatal MCMV infection developed the typical characteristics of EAE. Similar to MS, the MCMV-infected EAE-induced mice developed infi ltrates in the central nervous system (CNS) composed of similar percentages of CD4+ and CD8+ T cells. Th e infl ux of both Th 1 and Th 17 cells into the CNS of MCMV-infected EAE-induced mice was observed. Interestingly, the development of autoimmune neuroinfl ammation after latent MCMV infection was accompanied by a signifi cant infl ux of Tc17 cells (CD8+IL-17+ and CD8+RoRγt+) but not Tc1, cells. Our results suggest that latent MCMV infection aff ects the development of infl ammatory lymphocytes that exhibit encephalitogenic potential, thereby mediating increased CNS pathology following EAE induction, and that CMV represents a possible environmental factor in the pathogenesis of MS and other autoimmune diseases.