Mouse hepatitis virus type 4 (JHM strains). induced fatal central nervous system disease. I. genetic control and murine neuron as the susceptible site of disease

The tropism of neuronal cells explains the E + phenotype in susceptible MHV-4 infected mouse strains. This indicates the need for studying the specialized cells(s) involved in any disease process to understand the basic host restriction in susceptibility to disease. That principle is supported by our observations here and in studies with two other viruses. In an encephalomyocarditis virus model of diabetes, virus replication differed notably only in cultures of pancreatic beta cells from resistant and susceptible strains (33) . Using cytomegalovirus, Nedrud et al. (34) found significant differences in the amount of virus replicated by resistant and susceptible mice, but only in tracheal ring cultures, not in fihroblast cultures. The ability to generate homogeneous cultures of primary neuronal cells and the expectation of obtaining similar cultures for oligodendrocytes, now offers the opportunity to dissect the molecular basis of host restriction for virus induced demyelinating and degenerative diseases of the CNS. Further, definition of the genetic restriction in vitro using cells from recombinant inbred strains of mice should allow for allelic localization of the gene(s) involved in susceptibility.