Abstract

Tropical Spastic Paraparesis or HAM/TSP Human T-lymphotropic virus type-l-Associated Myelopathy/Tropical Spastic Paraparesis) is produced by the HTLV-I retrovirus, being characterized by a progressive distal degeneration of the motoneurons axons of the cortico-spinal tract. The virus in vivo infects mainly T CD4+ lymphocytes but not neurons. The secreted protein Tax seems to cause the pathology. In the present work, using PC12 cells as a model of differentiation to neuronal type induced by NGF, we determined the extracellular effect of secreted products from HTLV-I infected T cells (MT-2 cells). PC12 differentiation was followed in the presence of MT-2 secreted compounds or in the absence (with non infected K-562 cells) using a co-culture system separated by a semipermeable membrane. This treatment did not affect the initial process of extending neurite, whereas the further elongation was developed with a significantly reduced rate. Western blots of cell lysates during the differentiation period did not show changes in the levels of postranslational modifications of tubulin (tyrosynated, unstable microtubule marker and acetylated tubulin, stable microtubule marker) therefore, no correlation with the reduction in neurite elongation rate was found. The culture medium contains Tax protein and higher levels of Sema4D compared with the control coculture. Previous studies in our Laboratory have shown an interaction between Tax and Sema4D, this last protein is involved in neurite growth decrease. This data allows us to propose that extracellular Tax effects are produced through semaphorin receptors