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

Abstract

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