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 ti ssue inhibitors of metalloproteinases (TIMPs), are involved in modulat ion of the extracellular matrix, which participates in neural cell dif ferentiation, brain morphogenesis and tissue integrity. Metalloprotein ases and TIMPs are associated with inflammatory and degenerative proce sses in the central nervous system and are regulated by cytokines. Hum an retroviral infections are frequently associated with neurological d isturbances. In the present paper, we have studied the changes occurri ng in human primitive neuroectodermal cells following infection with h uman T cell lymphotropic virus type 1 (HTLV-I), a retrovirus responsib le for HTLV-l-associated myelopathy. Infected neural cells were found to have high metalloproteinase 9 (MMP9-92 kDa gelatinase) activity. MM P9 induction is dependent on HTLV-I infection of neural cells. In addi tion, soluble factors, especially tumour necrosis factor a, secreted b y infected cells, act as mediators of induction. HTLV-I infection also induces expression of RNA coding for tissue inhibitor of metalloprote inase 2. These observations indicate that HTLV-I infection selectively modulates the expression of molecules involved in the dynamic equilib rium between the synthesis and degradation of the neural cell matrix a nd leads to its remodelling, which modifies cell-cell interactions and cellular function.