MECHANISM OF THE INHIBITORY EFFECT OF CURDLAN SULFATE ON HIV-1 INFECTION IN-VITRO

To study the mechanism by which sulfated polysaccharides with 1,3-beta -D-glucan as a main chain exert anti-HIV-1 activity, we analyzed the e ffects of curdlan sulfate (CRDS) on HIV-1 infection of SupT-1 cells an d peripheral blood mononuclear cells. CRDS had no effect on virions, i nhibited weakly HIV-1 attachment to cells, and had to be present for 2 4 hr to achieve protection. Lack of HIV-1 DNA corresponding to the gag region in cells incubated with the virus and CRDS and inhibition of i nfection after addition of 2',3'-dideoxyinosine to cells treated with CRDS and HIV-1 for less than 24 hr suggest that CRDS delays events tha t precede and/or include reverse transcription. Analysis of the effect of CRDS on binding of HIV-1 neutralizing antibodies to gp120 demonstr ated that both the continuous epitopes on the V3 loop and the disconti nuous CD4 binding site of gp120 represent targets for CDRS. This inter action of CRDS with functional gp120 domains suggests that CRDS interf eres with the membrane fusion process during HIV-1 infection. Concentr ations of CRDS that were protective against infection with T cell- and macrophage-tropic HIV-1 isolates had less suppressive effects on T ce ll function in comparison with the related compound, dextran sulfate. (C) 1994 Academic Press, Inc.