Role of type I interferon in the Theiler's virus‐induced encephalitis, cellular infiltration to the CNS and function of immune cells

Abstract

Theiler's murine encephalomyelitis virus (TMEV), a single stranded RNA virus, causes a persistent infection in the central nervous system (CNS) and an immune‐mediated demyelination similar to human multiple sclerosis. To examine the role of type I interferon (IFN‐I)‐mediated signals in TMEV infection, mice lacking a subunit of the type I IFN receptor (IFN‐IR KO mice) were utilized. In contrast to the wildtype 129S2/SP mice unaffected after intracerebral infection with TMEV, IFN‐IR KO mice developed rapid fetal encephalitis accompanied with high viral load. IFN‐IR KO mice showed greater infiltration of immune cells to the CNS. Because of the higher levels of infiltration, the overall numbers of virus‐specific, IFN‐γ‐producing T cells were higher, despite the lower proportions of the virus‐specific infiltrating cells. Interestingly, altered expression patterns of MHC and co‐stimulatory molecules were observed in antigen presenting cells of IFN‐IR KO mice, leading to the cytokine production pattern of T cells differing from that of the wildtype control mice. These results suggest that IFN‐I‐mediated signals play important roles in cellular infiltration to the CNS and shaping protective immune responses, in addition to modulating viral replication. (Supported by RO1 NS28752, RO1 NS33008, RG 3392‐A5)