Induction of chronic inflammatory myelopathy in rats infected with recombinant HTLV-I

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Human T-lymphotropic virus type 1 (HTLV-I) is closely linked to HTLV-associated myelopathy (HAM), arthritis, uveitis and bronchial alveolitis. Immunological changes caused by HTLV-I infection may affect the condition, but the pathomechanism remains unknown. To elucidate the pathomechanism of these diseases, it is important to make animal models. Although induction of HAM-like paraparesis through experimental infection of WKA rats with HTLV-I has been reported, neither inflammatory changes nor alteration of the immune response has been observed in these animals. In addition, HTLV-I transgenic mice or rat has been reported to induce rheumatoid arthritis (RA)-like but not HAM-like myelopathy.We established many HTLV-infected T cell lines from HAM patients. One of them (Fuk line) inoculated to WKA rat caused RA-like arthritis. On the other hand, when MT-2, which is a HTLV-infected T cell line derived from ATL patient, was inoculated to WAK rats, they developed myeloneuropathy. These findings suggest that clinical expression in part depends on the HTLV-infected cell lines inoculated. Recently, it becomes technically possible to make infectious cDNA clones of HTLV-I. So, we tried to make infections cDNA clones from MT-2 cells and Fuk cells, respectively, to clarify which portion of HTLV-I genome play a pivotal role for the induction of myelopathy or arthritis. We sequenced the HTLV-I proviral DNA of MT-2 and Fuk line and found several mutations producing amino acid substitution in the pX region of HTLV-I derived from Fuk cells. It is now underway to make infections cDNA clone of HTLV-I of each cell lines.