MHV-68 induces central nervous system autoimmunity in an MBP-specific TCR transgenic mouse model of multiple sclerosis

Abstract Multiple Sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. Latent infection with Epstein-Barr virus (EBV) has been identified as necessary yet insufficient factor in development disease. Several groups have demonstrated that murine EBV analogue, MHV-68, exacerbates severity experimental encephalomyelitis (EAE). However, induction EAE requires immunization and does not fully replicate clinical features MS. We sought to develop virus-inducible model accurately represents MS etiology rely on classical immunization. Using transgenic mouse line myelin basic protein-specific T cell receptor, we found MHV-68 induces 72% infected mice. These mice exhibit such optic neuritis, incontinence, head tilt, which are commonly observed patients but EAE. This phenomenon was specific seen other viral pathogens including PR8 influenza. Our work demonstrates latent gammaherpesvirus can drive CNS autoimmunity genetically predisposed without prior induction, thus providing more natural National Institute Health R01AI140741-04