A rat model of human T lymphocyte virus type I (HTLV-I) infection: In situdetection of HTLV-I provirus DNA in microglia/macrophages in affected spinal cords of rats with HTLV-1-induced chronic progressive myeloneuropathy

To investigate the pathogenetic role of human T lymphocyte virus type I (HT LV-I) in central nervous system disease, a rat model for HTLV-I-associated myelopathy/tropical spastic paraparesis, designated as HAM rat disease, has been established. Wistar-King-Aptekman-Hokudai strain rats with induced HT LV-I infection develop a chronic progressive myeloneuropathy with parapares is of hind limbs after an incubation period of 15 months. In the affected s pinal cord in these rats, white matter degeneration, demyelination and vacu olar change with microglia/macrophage infiltration are present as are the p rovirus DNA and the virus mRNA. To identify infected cells in the affected lesions, we carried out in situ hybridization of amplified fragments of the provirus DNA by polymerase chain reaction on thin sections, plus immunohis tochemistry on the same sections. The provirus DNA was localized in some mi croglia/macrophages in the spinal cord lesion. In addition, the HTLV-I prov irus was clearly evident not only in ED-1-negative lymphoid cells but also in ED-1-positive macrophages from lymph nodes. These observations suggest t hat cells of microglia/macrophage lineage may be one of dominant viral rese rvoirs in the spinal cords and lymph nodes in HAM rat disease. These infect ed microglia/macrophages may relate to cause the myeloneuropathy through ne urotoxic cytokine synthesis.