Rabies and distemper exhibit distinct patterns of axonal damage and apoptotic cell death in the central nervous system of dogs and foxes.

Rabies is a fatal zoonosis caused by the rabies virus (RABV), which enters the central nervous system via a retrograde axonal pathway with histopathologically often very subtle but fatal polioencephalitis. Distemper is characterized by neuronal and/or axonal damage, as well as leukoencephalitis with demyelination in dogs and polioencephalitis without demyelination in foxes. This study aimed to compare the neuropathological lesions and the amount of axonal damage and apoptosis in the central nervous system of dogs and foxes infected with RABV or canine distemper virus (CDV), alongside non-infected control groups. Staining with hematoxylin and eosin, luxol fast blue-nuclear fast red, and immunohistochemistry for lyssaviral nucleoprotein, CDV nucleoprotein, β-amyloid precursor protein (a marker for early axonal damage) and active caspase-3 (a marker for apoptosis) was performed on archival formaldehyde-fixed, paraffin-embedded brain specimens. Dogs and foxes infected with RABV showed no change in the number of active caspase-3-immunoreactive cells and β-amyloid precursor protein-immunoreactive axons and no demyelinating areas. In contrast, CDV infection was characterized by an increase in active caspase-3-immunoreactive cells and β-amyloid precursor protein-immunoreactive axons in both species, and additionally demyelinating areas in the dog. These results suggest that RABV effectively evades recognition by intrinsic neuroaxonal antiviral mechanisms on its route to the central nervous system.