Biphasic disease of central nervous system induced in DBA/2 mice by the D variant of encephalomyocarditis virus (EMC-D).

DBA/2 mice infected with the D variant of encephalomyocarditis virus (EMC-D) (10(1) PFU/head) developed biphasic hind limb paralysis. At 12 days post inoculation (12 DPI), 60% of the infected mice developed hind limb paralysis and two-thirds of them showed recovery by 33 DPI. Thereafter, about 30% of the mice which once showed paralysis developed hind limb paralysis again by 56 DPI. Histopathologically, the spinal cord lesion of paralysed mice was characterized by demyelination associated with infiltration of macrophages in the funiculus lateralis and by degeneration of neurons in the cornu ventrale. Virus antigens were detected in the cytoplasm of degenerated neurons and oligodendrocytes in the demyelinated lesions from 3 to 14 DPI. At 28 DPI, demyelinated lesions reduced in size due to prominent remyelination. At 56 DPI, infiltration of mononuclear cells mainly composed of anti-L3T4-positive (CD4+) T cells were observed in the cornu ventrale of the mice showing recurrence of hind limb paralysis. These results suggested that the early paralysis was mainly due to demyelination in funiculus lateralis caused by EMC-D and macrophages and that the late paralysis was due to degeneration of motor neurons, probably brought about by CD4+ T cells.