Light and electron microscopic studies of ?nude? mice CNS after subcutaneous administration of the E variant of the encephalomyocarditis (EMC) virus

Abstract

Sixteen 3 month old "nude" mice, 24 of their litter mates and 30 Swiss mice were injected subcutaneously with 0.1 ml suspension of the E variant of the encephalomyocarditis (EMC) virus. While the mortality rate of the litter mates and Swiss mice during 5-7 days after inoculation was more than 40%, none of the "nude" mice died during the experiment. The surviving animals were sacrificed at 24 h intervals from day one to seven days after injection. Brain suspensions assayed for the presence of the virus yielded significant titers at 24 h in all groups, which increased during 7 days. The litter mates and Swiss mice showed proliferation of lymphocytes and microglial cells in the perivascular areas of the brain during the fifth to the seventh day. The "nude" mice, on the other hand, displayed no perivascular lymphocytic infilteration during the same periods. Ultrastructurally, all groups showed aggregates of ribosomes in the cytoplasmic matrix on the third day, which became enlarged in size on the 5th day. At 7 days, both litter mates and Swiss mice showed an increased number of necrotic cells, while these changes were not observed in the "nude" mice. These findings suggest that the high mortality rate in immunologically normal mice was related to the efforts of T cells to eliminate virus-infected cells and to produce extensive necrosis, while T cell-depleted animals showed good survival rates.

Oncolytic Effects of the E Variant of Encephalomyocarditis Virus to Human Neuroblastoma in in Vitro and in Vivo

“…The EMC virus causes a high mortality rate in mice [1,2,10,11,13]. However, an extensive clinical study has shown that this rodent virus is not implicated in any significant pathogenesis in man [1,14].…”

“…The virus has been investigated at our laboratory for many years [1][2][3][4][5][6][7][8][9][10][11][12]. The E variant (EMC-E) is highly neurotropic [1][2][3][4][5]7,[9][10][11]13] and usually not pathogenic to man [1,14]. The present investigation shows the oncolytic effects of the EMC-E virus on human neuroblastoma.…”

“…The virion is 20 to 30 nm in diameter and it consists of a capsid shell of 60 subunits arranged with icosahedral symmetry around a genome that has 11 variants [1]. The virus has been investigated at our laboratory for many years [1][2][3][4][5][6][7][8][9][10][11][12]. The E variant (EMC-E) is highly neurotropic [1][2][3][4][5]7,[9][10][11]13] and usually not pathogenic to man [1,14].…”