Inhibition of HIV-1 replication in H9 cells by nystatin-A compared with other antiviral agents.
Nystatin A was compared in vitro with amphotericin B, AZT, or foscarnet for their respective abilities to inhibit the replication of human immunodeficiency virus type 1 (HIV-1) in H9 cells. HIV-1-infected H9 cells were cultured for 7 days in the presence of each of these drugs, at various concentrations. Reverse transcriptase activity and p24 antigen production were quantitated. Untreated, HIV-1-infected H9 cells served as the control. Nystatin A inhibited viral replication most effectively at 10 micrograms/ml, a concentration that did not affect cell viability. Nystatin-A treatment inhibited RT activity by 85% and p24 production by 90%. These levels of inhibition were comparable to that mediated by amphotericin B, AZT, or foscarnet at 10, 25, and 50 micrograms/ml, respectively. Western blot analysis of the HIV-1-infected H9 cells treated with these drugs did not detect any expression of viral proteins. These findings were further corroborated by indirect immunofluorescence studies using monoclonal anti-gp120 FITC-conjugated antibodies and by polymerase chain reaction for proviral DNA analysis, using a 32P-labeled probe. These results suggest that Nystatin A merits attention as an antiviral drug for the treatment of HIV-1 infection. In vivo drug delivery by liposome encapsulation to overcome problems of bioavailability is currently under study.
Selvam
M P
MP
Laboratory of Immunochemistry, Food and Drug Administration, Rockville, MD 20852.
Blay
R A
RA
Geyer
S
S
Buck
S M
SM
Pollock
L
L
Mayner
R E
RE
Epstein
J S
JS
D000666:Amphotericin B / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D017245:Foscarnet / Q000494:pharmacology; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D009761:Nystatin / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
D000998:Antiviral Agents; D016655:HIV Core Protein p24; D018894:Reverse Transcriptase Inhibitors; D009761:Nystatin; D017245:Foscarnet; D015215:Zidovudine; D000666:Amphotericin B; D054303:HIV Reverse Transcriptase