Experimental rabies in skunks and foxes. Pathogenesis of the spongiform lesions

The pathogenesis of rabies spongiform lesions in striped skunks (Mephitis mephitis) and red foxes (Vulpes vulpes) was studied by light and electron microscopy and peroxidase-antiperoxidase immunocytochemistry. Studies in skunks included use of several street virus variants (different antigenic profiles as tested by monoclonal antibodies) different routes of inoculation (intranasal, intracerebral and intramuscular), immunosuppression of infected skunks, different preparations of virus (brain and salivary gland suspensions and infective tissue culture fluids), and sequential development of the lesions. Foxes (Vulpes vulpes) were infected intramuscularly with a street virus isolate. Except for the group of immunosuppressed skunks, all animals that developed clinical signs of rabies had encephalitis characterized by varying degrees of mononuclear perivascular cuffing, focal gliosis, and Negri bodies. Spongiform change occurred in the neuropil of the grey matter (especially thalamus and cerebral cortex) in rabid animals from all groups, but not in controls or exposed animals that did not develop rabies. Rabies antigen (detected by peroxidase-antiperoxidase immunocytochemistry) occurred only in small amounts in many thalami; some vacuolated areas were devoid of antigen. Ultrastructurally, there was a gradation in lesions from small to large membrane-bound vacuoles in cellular processes (mainly dendrites, less frequently axons) and to large tissue spaces containing granular and/or membranous material. These studies indicate that rabies spongiform change occurs in skunks given street virus of several different antigenic profiles and challenge virus standard rabies virus and that the distribution of the lesions has remarkable similarities to those of the traditional spongiform encephalopathies. The occurrence of the lesion is not affected by the immune response, the route of inoculation of virus, the preparation (suspension of salivary gland or brain, or tissue culture fluid), or the incubation period. The paucity of antigen in many thalami suggests that incorporation of viral components into vacuolar membranes is not necessary for development of the spongiform change. The development of the lesions includes formation of small membrane-bound vacuoles in cellular processes, rapid enlargement (less than 3 days) with compression of adjacent neural tissue, and rupture resulting in the large tissue spaces readily visible by light microscopy.