MECHANISM OF INHIBITORY EFFECT OF DEXTRAN SULFATE AND HEPARIN ON HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I (HTLV-I)-INDUCED SYNCYTIUM FORMATION IN-VITRO - ROLE OF CELL-TO-CELL CONTACT

Cell-to-cell contact is usually essential for syncytium formation by HTLV-I-infected cell lines. The present study was undertaken to determine the inhibitory effect of polyanionic compounds, dextran sulfate and heparin, on HTLV-I-induced syncytium formation, as demonstrated by the fusion of HTLV-I-infected cells with target cells. These two compounds almost completely blocked syncytium formation in the early phase of the reaction at a concentration of 125 mu g/ml, but dextran, as a control, did not inhibit it at concentrations up to 625 mu ug/ml. 50% inhibition of syncytium formation was detected at a concentration of 2 mu g/ml of dextran sulfate 5000, 3 mu g/ml of dextran sulfate 8000 and 8 mu ug/ml of heparin. The binding of radiolabeled HTLV-I-infected cells (HCT-1) to the target cells was inhibited by addition of dextran sulfate and heparin, and the inhibitory effects were concentration-dependent. No marked changes were detected in the expression of adhesion molecules on the virus-infected cells and target cells, and in the expression of envelope proteins on the virus-infected cells after exposing them to the polyanionic compounds. These results suggest that the blocking of cell-to-cell contact by polyanionic compounds, probably independent of surface adhesion molecules, is important for their inhibitory effect on HTLV-I-induced syncytium formation.