While there is no evidence of an active, cytolytic viral infection in the central nervous system (CNS) in multiple sclerosis (MS), viruses may participate in the pathogenesis of MS in one or more ways. Many viruses have sequence homologies with myelin proteins, and through the mechanism of molecular mimicry viral infections might stimulate T cells specific for myelin antigens, thereby initiating a T cell-mediated autoimmune attach on CNS myelin. Viral antigens expressed in the CNS during chronic, non-cytolytic infection might serve as targets of a viral-specific T cell response resulting in demyelination. Finally, a viral infection that initially causes demyelination, either through a cytolytic infection of oligodendrocytes or as a target of a T cell response, could secondarily elicit an autoimmune reaction to myelin antigens through the mechanism of epitope spread. Acute onset demyelinating encephalomyelitis with morphologic features similar to MS was first observed in group-housed Japanese macaques in 1986. The incidence of the disease peaked the following year, affecting 3% of the population. Subsequently, approximately 1% of the population develop demyelinating encephalomyelitis annually. A novel herpesvirus was initially recovered from an animal that developed demyelinating encephalomyelitis in 1994. This isolate has been characterized as a member of the rhadinovirus family of gamma herpesvirus and is closely related to rhesus rhadinovirus and human herpesvirus-8. Serologic studies reveal that 100% of the animals more than one year of age are infected with most animals seroconverting by 130 days of age. Approximately 10% of the seroconverted animals have recoverable virus in their peripheral blood mononuclear cells for years, indicating chronic active infection. Animals that develop demyelinating encephalitis segregate to the subpopula tion of animals with chronic active herpesvirus infection; however, active herpesvirus infection has not been demonstrated in the CNS. This pilot study will further characterize the immunopathology of herpesvirus-associated demyelinating encephalomyelitis (HVDE) in Japanese macaques, assess serologically for anti-myelin antibodies in animals that developed HVDE and establish whether or not the rhadinovirus genome resides within the CNS of these animals. FUNDING Department of Veterans Affairs Research Enhancement Award Program PUBLICATIONS None
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