AUROTHIOLATES INHIBIT HIV-1 INFECTIVITY BY GOLD(I) LIGAND-EXCHANGE WITH A COMPONENT OF THE VIRION SURFACE

Aurothioglucose and aurothiomalate have anti-HIV-1 activity in vitro. Antiviral activity requires the formation of a reactive intermediate with a molar equivalent amount of a thiol ligand. This activates gold(I) ligand exchange between the reactive species bis(thiolato)gold(I) and acidic thiol groups exposed on the surface of proteins. Bis(thioglucose)gold(I) (bisAuTG) which is formed by the reaction of molar equivalent amounts of aurothioglucose and 1-thio-β-D-glucose completely protected MT-4 and CEM cells against HIV-1(NL4-3)-induced cytopathogenicity. Although bisAuTG is an inhibitor of human immunodeficiency virus-1 (HIV-1) reverse transcriptase in a cell-free assay, its antiviral effect is due to modification of a surface component of the virion. The HIV-1 strain NL4-3 is 200-fold more sensitive to inhibition of infectivity by bisAuTG than are the strains MN, RF, and SF-2, HIV-1(NL4-3) has a unique cysteine residue close to the amino terminus of its gp41 envelope glycoprotein (residue 532 of gp160) which we hypothesize is the target of bisAuTG binding. Mutation of that residue alters HIV-1(NL4-3) infectivity and dominantly suppresses virus assembly when coexpressed with the wild-type NL4-3 genome. We show that bisAuTG treatment releases gp120 from the surface of cells expressing wild-type HIV-1(NL4-3) envelope glycoprotein, but it does not release gp120 if Cys532 is mutationally altered to Ala. Thus, the antiviral effect of bisAuTG on HIV-1(NL4-3) is due to an effect on the association of gp120 with gp41. © 1993 Academic Press, Inc.