Experimental old dog encephalitis (ODE) in a gnotobiotic dog

Experimental infection of a gnotobiotic Beagle dog with the neurovirulent R252 strain of canine distemper virus (R252-CDV) resulted in long-term central nervous system (CNS) infection; cerebral and brain stem lesions were consistent with old dog encephalitis (ODE). Eight clinical cycles of relapsing cortical and subcortical signs were documented over 33 months and were corroborated by the presence of both chronic and active inflammatory demyelinating lesions within the neuraxis. Immunocytochemistry revealed that CDV antigen was restricted to neurons. Attempts to use fresh brain tissue to directly transmit the infection to CDV-susceptible gnotobiotic dogs were unsuccessful. Reisolation of infectious virus from the infected dog required prolonged culture and coculture of brain explant cells with CDV-susceptible Vero cell monolayers. These findings demonstrate that ODE is a variant of virulent CDV-induced canine neurologic disease that can evolve de novo within the CNS of subclinically infected dogs in the absence of external sources of reinfection. The highly cell-associated nature of the virus, when first recovered from this dog, suggests that the virus was present within the CNS in a replication-defective form.