Central nervous system lesions in rats infected with Friend murine leukemia virus-related PVC441: ultrastructural and...

Newborn F344 rats were injected intraperitoneally with PVC441 virus, a neuropathogenic variant of Friend murine leukemia virus, and developed paraparesis of hind limbs 35-40 days after infection. Immunohistochemical study using monoclonal anti-PVC441 antibody revealed that in the central nervous system endothelial cells but not neuronal or glial cells were infected with PVC441 virus. The major pathological changes were myelin vacuolation and oligodendrocyte degeneration in the white matter at the white-gray border zone. Anterior and lateral funiculi and intercalated myelin of anterior horns were dominantly affected in the spinal cord from the sacral to cervical level. The midbrain was also vacuolated. An ultrastructural study demonstrated that many viral particles were present outside the endothelial cells but only sparsely inside endothelial cells and pericytes. Endothelial cell membranes and tight junctions were also disrupted. Immunohistochemical studies with antibodies against major histo-compatibility complex class Ia, intercellular adhesion molecule-I, glial fibrillary acidic protein, neurofilament protein, CD3 and OX42 revealed the presence of abundant microglia but not of lymphocytes or polymorphonuclear cells in the lesions. Axonal degeneration and astrogliosis were mild in degree. These pathological changes explain the observed spastic paraparesis in the rats, and represent a good model of spongiform diseases of the human central nervous system of retroviral origin, such as human T cell leukemia virus-associated myelopathy and AIDS.