Modulation of the Antiviral Activity of Poly (A-U) by Ethidium Bromide and Propidium Iodide

Abstract

The role of ethidium bromide (EB) and propidium iodide (PI) in modulating the antiviral and interferon-inducing activities of poly(adenylate-uridylate) (poly (A-U)) was examined using the human foreskin fibroblast-vesicular stomatitis virus (HSF-VSV) bioassay system in which the concentration of poly (A-U) was fixed at 0.05 mM or 0.2 mM while the EB or PI concentration was varied to produce variable EB (or PI)/ribonucleotide ratios ranging from 1:16 to 2:1. EB, PI and poly (A-U) tested individually were not efficacious antiviral agents. When poly (A-U) was combined with the ethidium bromide or propidium iodide the antiviral activity was potentiated 15- to 22-fold at EB (or PI)/ribonucleotide ratios in the region of 1/4. The interferon-inducing activity of the EB (or PI)/poly (A-U) combinations were equal to the sum of the interferon-inducing activity of the poly (A-U) and the EB or (PI). These results indicate that the EB and PI potentiate the antiviral activity of the poly (A-U) without superinduction of interferon. The direct viral inactivation study demonstrated that EB, PI, poly (A-U) and the EB (or PI)/poly (A-U) combinations did not inactivate the VSV at concentrations near the 50% viral inhibitory dose.