INDUCTION OF MMP9 (92 KDA GELATINASE) ACTIVITY AND EXPRESSION OF TISSUE INHIBITOR OF METALLOPROTEINASE-2 MESSENGER-RNA (TIMP-2) IN PRIMITIVE NEUROECTODERMAL CELLS INFECTED WITH RETROVIRUS HTLV-I

Matrix-degrading proteases, including metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), are involved in modulation of the extracellular matrix, which participates in neural cell differentiation, brain morphogenesis and tissue integrity. Metalloproteinases and TIMPs are associated with inflammatory and degenerative processes in the central nervous system and are regulated by cytokines. Human retroviral infections are frequently associated with neurological disturbances. In the present paper, we have studied the changes occurring in human primitive neuroectodermal cells following infection with human T cell lymphotropic virus type 1 (HTLV-I), a retrovirus responsible for HTLV-l-associated myelopathy. Infected neural cells were found to have high metalloproteinase 9 (MMP9-92 kDa gelatinase) activity. MMP9 induction is dependent on HTLV-I infection of neural cells. In addition, soluble factors, especially tumour necrosis factor a, secreted by infected cells, act as mediators of induction. HTLV-I infection also induces expression of RNA coding for tissue inhibitor of metalloproteinase 2. These observations indicate that HTLV-I infection selectively modulates the expression of molecules involved in the dynamic equilibrium between the synthesis and degradation of the neural cell matrix and leads to its remodelling, which modifies cell-cell interactions and cellular function.