Comparison of the effect of FK506 and cyclosporin A on virus production inH9 cells chronically and newly infected by HIV-1

The presence of FK506-binding protein-12 was demonstrated in virions of HIV -I, although its concentration was lower than that of cyclophilin A. The ef fect of two inhibitors of the peptidyl-prolyl cis-trans isomerases FK506 an d cyclosporin A (CsA) was studied in H9 cells that were chronically infecte d by HIV-I. Both drugs inhibited virus production in the infected cells in a concentration-dependent manner, by decreasing the number of the producing cells. FK506 did not have an effect on Gag processing, based on the p24 an tigen content of virions produced in the presence of this drug. Furthermore , FK506 treatment of uninfected H9 cells did not diminish their susceptibil ity toward HIV-1 infection, whereas CsA treatment decreased the degree of H IV-1 infection with an IC50 of 1-2 mu g/ml. Also, pretreatment of the virus with CsA decreased its infectivity in HeLaCD4-LTR/beta-gal cells; in contr ast, at concentrations up to 10 mu g/ml, FK506 did not have an effect. Our findings on the antiviral activity of FK506 and CsA suggest that FK506 is e ffective only in chronically infected cells, by selectively inhibiting the growth of HIV-1 infected cells, whereas CsA has a specific effect on virus replication.