Exacerbation of experimental autoimmune encephalomyelitis in rodents infected with murine gammaherpesvirus‐68

Viral infections have long been suspected to play a role in the pathogenesis of multiple sclerosis. In the present study, two different rodent models of experimental autoimmune encephalomyelitis (EAE) were used to demonstrate the ability of murine gammaherpesvirus‐68 (γHV‐68) to exacerbate development of neurological symptoms. SJL mice received UV‐inactivated γHV‐68 or intranasalγHV‐68, followed by immunization against proteolipid‐protein peptide 139–151. Infected mice became moribund within 10 days post‐immunization, whereas mice exposed to UV‐inactivated γHV‐68 recovered. In the second model, Lewis rats were exposed to UV‐inactivated γHV‐68 or to γHV‐68, followed by passive transfer of encephalitogenic T lymphocytes specific for myelin basic protein. Consistently, infected rats had higher clinical scores, and this result was observed during acute or latent γHV‐68 infection. It is unlikely that this γHV‐68‐induced exacerbation was due to significant viral replication within the central nervous system since nested PCR, viral plaque assays, and infectious‐centers assays demonstrated no detectable virus in spinal cords or brains of infected rodents undergoing EAE. Taken together, these studies demonstrate increased clinical symptoms of EAE in rodents infected by a gammaherpesvirus that has a limited ability to invade the central nervous system.