Abundant expression of viral nucleoprotein mRNA and restricted translation of the corresponding viral protein in inclusion body polioencephalitis of canine distemper.

Brain and other tissues of three dogs aged 4-21 months with inclusion body polioencephalitis caused by canine distemper virus (CDV) were examined for CDV nucleoprotein (N) antigen and mRNA distribution. Two animals (nos 3 and 1) had suddenly shown central nervous system (CNS) signs 4 days and 5 months, respectively, after vaccination with a modified live CDV vaccine; animal no. 2 had shown similar signs 4 weeks after vaccination with an unknown product. Lesions in the CNS, which were restricted to the grey matter, occurred most frequently in the diencephalon, mesencephalon, medulla oblongata and, in one animal, in the cerebral cortex. Changes were characterized by mild to moderate perivascular lymphohistiocytic cuffs, loss of neurons, neuronal necrosis, glial nodules, and oedema. Intranuclear and cytoplasmic inclusion bodies, especially prominent in neurons, were observed. By in-situ hybridization, CDV N mRNA expression was confirmed with a non-radioactively labelled N-specific mRNA probe. The corresponding RNA translation product was detected immunohistochemically with a proteinspecific monoclonal antibody. Viral antigen and mRNA were observed in the same cell types and brain compartments. However, the number of cells expressing N mRNA exceeded the number of cells containing viral antigen greatly in two animals and slightly in one. Some areas with abundant viral mRNA expression were almost completely devoid of viral antigen. mRNA and the corresponding translation product were demonstrated in neurons and less frequently in astrocytes, but not in perivascular inflammatory cells. It would appear that distemper inclusion-body polioencephalitis may be due to a non-productive CDV infection of neurons, characterized by abundant expression of CDV N mRNA and reduced translation of the corresponding viral protein. These findings suggest that in distemper the pathogenesis of grey-matter lesions differs substantially from that of white-matter lesions, which constitute the most common manifestation of distemper encephalitis.