EFFECT OF SERINE-PROTEASE INHIBITOR, N-ALPHA-TOSYL-L-LYSYL CHLOROMETHYL KETONE (TLCK), ON CELL-MEDIATED AND CELL-FREE HIV-1 SPREAD

The effect of a serine protease inhibitor, N-alpha-tosyl-L-lysyl-chloromethyl ketone (TLCK), on cell adhesion and resulting cell-to-cell HIV-1 transmission was examined. Cell-mediated viral spread was blocked by 10(-4) M TLCK-the nontoxic dose at which the maximum inhibition of cell adhesion was achieved. TLCK (10(-4)-10(-8) M range) exhibited a similar dose-dependent effect when tested against cell-free virus infection. These findings suggest that TLCK acts by preventing both cell-cell adhesion and viral binding to the target cell. The effect of TLCK could be attributed to an irreversible modification of surface and/or intracellular proteases required for functional activation of HIV-1 envelope glycoproteins. (C) 1994 Academic Press, Inc.