Chronic progressive myeloneuropathy in WKAH rats induced by HTLV-I infection as an animal model for HAM/TSP in humans

Abstract

We immortalized rat T cells with helper-inducer phenotype, by HTLV-I superinfection. These immortalized cells had integrated human T-cell lymphotropic virus (HTLV)-I provirus genomes and showed nuclear polymorphism resembling adult T-cell leukemia cells. Among HTLV-I carrier rats of several strains, only WKAH strain rats developed a chronic progressive myeloneuropathy with spastic paraparesis of the hind limbs (HAM rat disease), after a long incubation period. Clinical and neuropathological features of HAM rat disease generally mimic those of HAM/TSP in humans, although T-cell infiltration is absent in the affected spinal cord lesions in the case of HAM rat disease. The collective evidence suggests that the major pathogenetic pathway of HAM rat disease appears to be closely related to apoptotic death of myelin-forming cells, oligodendrocytes and Schwann cells. Putative factors involved in apoptosis of these cells are discussed in relation to HTLV-I infection.