Experimental canine distemper encephalomyelitis in neonatal gnotobiotic dogs. A sequential ultrastructural study

The ultrastructural morphogenesis of neuronal degeneration and necrosis and patterns of associated myelin and axonal degeneration were studied in gnotobiotic dogs neonatally infected with neurovirulent R252 strain of canine distemper virus (CDV-R252). Distemper virus-infected neurons underwent a distinct sequence of ultrastructural changes culminating in direct viral-induced necrosis beginning after 21 days post inoculation (DPI). Viral-induced neuronal cytolysis occurs apparently independently of anti-viral immune mechanisms of immunologic destruction. Viral nucleocapsid aggregates in postsynaptic axosomatic and axodendritic complexes and in structurally intact axons provided morphologic evidence for viral-induced functional modulation of synaptic transmission and possible trans-synaptic interneuronal viral spread. There were secondary degenerative axonal and myelin changes, particularly in heavily myelinated tracts. There was no evidence of primary demyelination. Active phagocytosis of degenerating axons and myelin debris in foci of virus-associated necrosis was apparently restricted to CDV-containing macrophages. Demonstration of a productive CDV infection of choroid plexus epithelium 10 DPI and thereafter was identified as an intracranial source of free infectious virus.