HUMAN T-LYMPHOCYTE VIRUS TYPE I-INDUCED MYELONEUROPATHY IN RATS - IMPLICATION OF LOCAL ACTIVATION OF THE PX AND TUMOR-NECROSIS-FACTOR-ALPHAGENES IN PATHOGENESIS

The pathogenetic roles of human T lymphocyte virus type I (HTLV-I) and cytokines were investigated in HTLV-I-induced myeloneuropathy in Wist ar-King-Aptekman-Hokudai rats. In the nervous system, pX messenger RNA s of HTLV-I were selectively expressed in the diseased spinal cord and peripheral nerves but not in the unaffected cerebrum and cerebellum, even though proviral DNAs were consistently identified in these tissue s. Among several cytokines examined, mRNA expression and production of tumor necrosis factor (TNF)-alpha in the spinal cord and cerebrospina l fluid correlated positively with the development of spinal cord lesi ons. The collective evidence strongly suggests that selective activati on of HTLV-I, in particular Tax expression and production of TNF-alpha induced by HTLV-I infection in target spinal cord and peripheral nerv es, is causally related to apoptotic death of oligodendrocytes and Sch wann cells, a major pathogenetic pathway of the HTLV-I-induced myelone uropathy.