Pathogenic Properties of Encephalomyocarditis Virus Plaque Variants.

The pathogenic properties of two plaque-variants (r+ and r) of the EMC virus were investigated in mice of different ages. Both variants caused lethal infections in newborn animals after i.c., i.p. and s.c. inoculation. They also were virulent for 3-week mice when introduced i.c. However, the r+ variant was non-pathogenic in adult animals injected by peripheral routes. The two variants grew for extended periods of time in soft tissues at the s.c. site of inoculation. Although viremia and central nervous system disease appeared in animals receiving r, a generalized infection failed to develop in those inoculated with r+. No evidence was found to indicate that interferon or antibody altered the pathogenicity of this variant. Revertant PFU invariably developed when r+ variant was grown in cell cultures; virulent r or r-like viruses comprised 0.5 to 2% of the PFU in r+ pools. Accordingly, it was necessary to employ fewer than 100 PFU of r+ to obtain a uniform population of the variant for pathogenicity studies. When larger dosages were introduced s.c. into animals, revertants disseminated and caused a lethal generalized infection. Growth of r and r-like revertants was favored in animal tissues and they were selected during serial passage in vivo. Since r+ variant multiplied in L cells at a faster rate and produced more PFU per cell than r, passage of virus in cell cultures yielded a predominant population of r+. Thus, the “wild” form of this strain of EMC virus differed according to the system in which it was maintained.