title: Multiple sclerosis and virus induced immune responses: autoimmunity can be primed by molecular mimicry and augmented by bystander activation.
abstract: Polymicrobial infections have been associated with plausible immune mediated diseases, including multiple sclerosis (MS). Virus infection can prime autoimmune T cells specific for central nervous system (CNS) antigens, if virus has molecular mimicry with CNS proteins. On the other hand, infection of irrelevant viruses will induce two types of cytokine responses. Infection with a virus such as lymphocytic choriomeningitis virus (LCMV), can induce interferon (IFN)-alpha/beta production and suppress autoimmunity, while infection with a virus, such as murine cytomegalovirus (MCMV), can activate natural killer (NK), NKT and dendritic cells, resulting in interleukin (IL)-12 and IFN-gamma production. These cytokines can cause bystander activation of autoreactive T cells. We established an animal model, where mice infected with vaccinia virus encoding myelin protein can mount autoimmune responses. However, the mice develop clinical disease only after irrelevant immune activation either with complete Freund's adjuvant or MCMV infection. In this review, we propose that a combination of two mechanisms, molecular mimicry and bystander activation, induced by virus infection, can lead to CNS demyelinating diseases, including MS. Viral proteins having molecular mimicry with self-proteins in the CNS can prime genetically susceptible individuals. Once this priming has occurred, an immunologic challenge could result in disease through bystander activation by cytokines.
authors.affiliation: University of Utah School of Medicine, Department of Neurology, 30 North 1900 East, Room 3R330, Salt Lake City, UT 84132-2305, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: McCoy
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tsunoda
authors.forename: Robert S
authors.initials: RS
authors.lastname: Fujinami
mesh_terms: D000818:Animals; D006801:Humans; D018716:Molecular Mimicry / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*