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.
Bourinbaiar
A S
AS
Department of Biochemistry, New York University Medical Center, New York 10016.
Nagorny
R
R
D002448:Cell Adhesion / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D013601:T-Lymphocytes / Q000382:microbiology*; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D014107:Tosyllysine Chloromethyl Ketone