Comparison of the effect of FK506 and cyclosporin A on virus production in H9 cells chronically and newly infected by HIV-1.
The presence of FK506-binding protein-12 was demonstrated in virions of HIV-1, although its concentration was lower than that of cyclophilin A. The effect of two inhibitors of the peptidyl-prolyl cis-trans isomerases FK506 and cyclosporin A (CsA) was studied in H9 cells that were chronically infected by HIV-1. 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 antigen content of virions produced in the presence of this drug. Furthermore, FK506 treatment of uninfected H9 cells did not diminish their susceptibility toward HIV-1 infection, whereas CsA treatment decreased the degree of HIV-1 infection with an IC(50) of 1-2 microg/ml. Also, pretreatment of the virus with CsA decreased its infectivity in HeLaCD4-LTR/beta-gal cells; in contrast, at concentrations up to 10 microg/ml, FK506 did not have an effect. Our findings on the antiviral activity of FK506 and CsA suggest that FK506 is effective only in chronically infected cells, by selectively inhibiting the growth of HIV-1 infected cells, whereas CsA has a specific effect on virus replication.
Briggs
C J
CJ
Molecular Virology and Carcinogenesis Laboratory, ABL-Basic Research Program, Frederick, Maryland, USA.
Ott
D E
DE
Coren
L V
LV
Oroszlan
S
S
Tözsér
J
J
D019380:Anti-HIV Agents / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016655:HIV Core Protein p24 / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D020104:Immunophilins / Q000032:analysis; D016559:Tacrolimus / Q000494:pharmacology*; D022021:Tacrolimus Binding Proteins; D014407:Tumor Cells, Cultured
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D016572:Cyclosporine; D054303:HIV Reverse Transcriptase; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins; D016559:Tacrolimus