Characterization of Canine Distemper Viruses Adapted to Neural Cells and Their Neurovirulence in Mice

Abstract

Interaction of the Onderstepoort strain of canine distemper virus (CDV)with three established human neural cells, i.e. IMR-32 neuroblastoma, 118-MGC glioma and KG-I oligodendroglioma, was examined, and adaptation of CDV to these cells was also attempted. The unadapted virus was found to grow at relatively low titers in the three neural cells inducing moderate to minimal cytopathic effects (CPE). The virus was successfully grown at high titers in these cells after 8 to 10 passages. Biological characteristics such as growth rate, morphology of CPE and plaque size changed after adaptation. Analysis by SDS-polyacrylamide gel electrophoresis, however, failed to show any difference in the molecular weight of component proteins among the unadapted and three adapted viruses.Inbred DDD strain of mice developed clinical signs after intracerebral inoculation with the unadapted virus but most of them survived with histological lesions of encephalitis. Neuroblastoma-adapted virus induced only transient clinical signs in some animals with mild encephalitic lesions in the gray matter. Increases in neurovirulence were found for viruses adapted to glioma and oligodendroglioma cells. Almost all mice inoculated with these two viruses at 3 weeks of age died within 8 days with histological lesions consisting of hyperemia, edema, severe degeneration of nerve cells and a few giant cells. Demyelinating lesions in the absence of inflammatory changes were observed in the cerebellum, pons and medulla oblongata of animals inoculated with oligodendroglioma-adapted virus.

Characterization of Canine Distemper Viruses Adapted to Human Neural Cells

“…Variation in the H proteins was observed by peptide mapping, but not by 2-dimensional gel electrophoresis, in which H protein was not detected except for the MGC-virus. The absence of H proteins of the three viruses in 2-dimensional gel electrophoresis may be due to diffusion in the first dimension, because H proteins of these viruses have been clearly detected by SDS-PAGE (31). H proteins of measles virus, HN proteins of other paramyxoviruses are receptor-binding proteins in virus adsorption; F proteins of paramyxoviruses are responsible for the penetration of viruses into the cells and virus-induced cellfusion and hemolysis (4).…”

“…By SDS-PAGE, the MW of viral proteins in infected cells among these adapted viruses has been found to be identical (31).…”

“…In mice, the adapted viruses showed a neurovirulence different from that of the original virus. The glioblastoma-adapted virus induced fatal necrotizing encephalopathy that affected nerve and glial cells; the oligodendroglioma-adapted virus induced spongy degeneration, demyelination, and axonal degeneration in addition to fatal necrotizing encephalopathy; and the neuroblastoma-adapted virus induced diffuse nerve cell degeneration (18,31).To understand the basis of such differences in terms of the biological properties 1211 …”

“…The resemblance of the lesions of old-dog encephalitis to those of multiple sclerosis (l) and the epidemiological considerations that suggest the possible involvement of CDV in the etiology of multiple sclerosis (5,6) led us to study the interaction between CDV and human neural cells. We have adapted CDV to human glioblastoma, oligodendroglioma, and neuroblastoma cells (31). The adapted viruses replicated more efficiently, producing larger plaques in the neural cells, than the original virus.…”

Growth of Defective Subacute Sclerosing Panencephalitis Viruses in Human Neural Cells and Their Neurovirulence in Mice

“…Such changes in neurovirulence after passage in different cells have been reported for canine distemper and rabies viruses. After adaptation of canine distemper virus to the same three human neural cells types used in this study, increased neurovirulence in mice was observed (Yoshikawa et al, 1983). Attenuated rabies virus was reported to show increased neurovirulence after a few passages in neuroblastoma cells, and it was speculated that randomly occurring virulent virus mutants replicated selectively in neuroblastoma cells (Clark, 1978(Clark, , 1980.…”