Experimental old dog encephalitis (ODE) in a gnotobiotic dog

Area of Science:

• Veterinary Neurology
• Virology
• Immunology

Background:

• Canine distemper virus (CDV) causes severe neurological disease in dogs.
• Old Dog Encephalitis (ODE) is a chronic neurological condition in dogs with unclear etiology.
• The R252 strain of CDV is known for its neurovirulence.

Purpose of the Study:

• To investigate the pathogenesis of canine distemper virus-induced Old Dog Encephalitis.
• To characterize the long-term central nervous system (CNS) infection by CDV.
• To understand the viral dynamics and evolution within the CNS.

Main Methods:

• Experimental infection of gnotobiotic Beagle dogs with neurovirulent R252-CDV.
• Longitudinal clinical monitoring and neurological examination over 33 months.
• Histopathological examination of brain and spinal cord tissues.
• Immunocytochemistry to detect viral antigens within CNS tissues.
• Attempts at direct viral transmission and virus reisolation from infected brain tissue.

Main Results:

• Long-term CNS infection with R252-CDV resulted in lesions consistent with ODE.
• Eight clinical cycles of relapsing neurological signs were observed over 33 months.
• Chronic and active inflammatory demyelinating lesions were found throughout the neuraxis.
• CDV antigen was exclusively detected within neurons.
• Direct transmission to susceptible dogs using fresh brain tissue was unsuccessful.
• Virus reisolation required prolonged culture and co-culture techniques, suggesting a cell-associated, possibly replication-defective form.

Conclusions:

• Old Dog Encephalitis can arise de novo within the CNS as a variant of virulent CDV infection.
• The virus evolves within the CNS, independent of external reinfection.
• The highly cell-associated nature of the recovered virus suggests a unique replication strategy within the CNS.