Inhibition of HIV-1 Replication in H9 Cells by Nystatin-A Compared with Other Antiviral Agents

Abstract

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.

Amphotericin B derivative blocks human immunodeficiency virus type 1 entry after CD4 binding: effect on virus-cell fusion but not on cell-cell fusion

“…MS8209 may therefore be useful to define the early steps of HIV-1 entry and their viral and cellular requirements. Amphotericin B and its derivatives, as well as nystatin A, are structurally related to MS8209 and also exert an antiviral effect on HIV-1 (28,31). Although a detailed study of their mechanisms of action has not yet been reported, our preliminary experi-ments indicate a mode of action similar to that of MS8209.…”

HIV-1 preferentially binds receptors copatched with cell-surface elastase

“…Nystatin is a cholesterol-binding antibiotic that selectively disrupts HIV-1 receptors residing on cholesterolcontaining platforms 25 and has been demonstrated to interfere with in vitro HIV-1 infectivity (IC 50 ϭ 4 M) in H9, HUT-78, and U937 cells, but has little effect in vivo except against candidiasis. 26 HLE and CXCR4 copatching stimulated by ␣ 1 PI was found to be completely abrogated by pretreating for 60 minutes with 50 M nystatin (data not shown).…”

The Role of Lipids in Retrovirus Replication

“…Because virions bud from cholesterol-rich microdomains, cholesterol depletion results in a reduced amount of cholesterol on the viral membrane, which in turn inhibits viral infectivity. Cholesterol-chelating compounds like nystatin have also been reported to inhibit HIV-1 infectivity [42,47]. Recently, we have shown that the cholesterol-binding compound amphotericin B methyl ester (AME), a water-soluble derivative of amphotericin B, inhibits HIV-1 entry [48–51].…”