EAE symptoms are enhanced by gammaherpesvirus latenlty infetected memory B cells (VIR1P.1143)

Abstract

Abstract While the description of the genetic and environmental factors responsible for the onset of Multiple Sclerosis has remained elusive, it is believed that previous infection with Epstein Barr Virus (EBV) plays an important role in the development of MS. Our lab has hypothesized that latent EBV infection alters the immune system’s response in genetically predisposed individuals, thereby exacerbating autoimmunity. The study of this relationship is difficult, however, since EBV only infects humans. To address this question we previously developed a murine model where latent infection with gamma herpesvirus 68 (γHV-68), the murine homolog to EBV, enhances the symptoms of experimental autoimmune encephalomyelitis (EAE), which closely resembles human MS pathogenesis. These enhanced symptoms are driven by the upregulati/on of CD40 on dendritic cells in latently infected mice, which drives the priming of a strong Th1 response as well as a decrease in Treg frequencies. Latency of γHV-68 mainly occurs in memory B cells. Here, we demonstrate that latently infected memory B cells are capable of enhancing EAE symptoms when transferred from mice latently infected with γHV-68 into uninfected mice. To understand the impact of γHV-68 on B cells, we propose a mechanism where type 1 interferons play an important role in skewing a Th1 response in latently infected mice. This is a novel mechanism that describes how EBV latency can spur the onset of MS and potentially other autoimmune diseases.