EXTRACELLULAR MATRIX-REMODELING METALLOPROTEINASES AND INFECTION OF THE CENTRAL-NERVOUS-SYSTEM WITH RETROVIRUS HUMAN T-LYMPHOTROPIC VIRUS TYPE-I (HTLV-I)

Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are invo lved in physiological processes and contribute to the phenotype of sev eral pathological conditions associated with uncontrolled tissue degra dation. In the central nervous system (CNS), MMPs are thought to play a role in cell migration and synaptic plasticity. We have investigated the expression, regulation and possible role of MMPs and TIMPs during infection of glial cells with human T-lymphotropic virus type 1 (HTLV -I), the causative agent of a progressive chronic myelopathy, TSP/HAM. The major alteration consists in a high increase in MMP-9 secretion a nd TIMP-2 mRNA expression. Cytokines TNF alpha and IL1 alpha, induced in glial cells during HTLV-I infection, promote the upregulation of MM P-9. Tn addition, cerebrospinal fluid from TSP/HAM patients contain hi gh MMP-9 level. The exact role of dysregulated MMPs/TIMPs in the patho genesis of TSP/HAM is not known; however, functions of these proteases in physiological processes should provide valuable clues. MMPs can af fect the blood-brain barrier and the intercellular connectivity by deg rading the extracellular matrix of endothelial and neural cells, They can be involved in autoimmunity by generating preformed specific pepti des from myelin components. Finally, they can direct and prolong TNF a ctivity in the CNS by converting its inactive precursor into active mo lecules. Copyright (C) 1996 Elsevier Science Ltd.