CHRONIC PROGRESSIVE MYELONEUROPATHY IN WKAH RATS INDUCED BY HTLV-I INFECTION AS AN ANIMAL-MODEL FOR HAM TSP IN HUMANS/

We immortalized rat T cells with helper-inducer phenotype, by HTLV-I s uperinfection. These immortalized cells had integrated human T-cell ly mphotropic virus (HTLV)-I provirus genomes and showed nuclear polymerp hism resembling adult T-cel leukemia cells. Among HTLV-I carrier rats of several strains, only WKAH strain rats developed a chronic progress ive myeloneuropathy with spastic paraparesis of the hind limbs (HAM ra t disease), after a long incubation period. Clinical and neuropatholog ical features of HAM rat disease generally mimic those of HAM/TSP in h umans, although T-cell infiltration is absent in the affected spinal c ord lesions in the case of HAM rat disease. The collective evidence su ggests that the major pathogenetic pathway of HAM rat disease appears to be closely related to apoptotic death of myelin-forming cells, olig odendrocytes and Schwann cells. Putative factors involved in apoptosis of these cells are discussed in relation to HTLV-I infection.