Enhancement of the Antiviral Activity of Poly (A-U) by Adriamycin and Daunomycin

Abstract

The role of adriamycin (ADR) and daunomycin (DMN) in modulating the antiviral activity of poly (adeylate-uridylate) (poly (A-U)) was examined using a human foreskin fibroblast – vesicular stomatitis virus (HSF-VSV) bioassay in which the concentration of poly (A-U) was fixed at 0.05 mm or 0.2 mm while the ADR or DMN concentration was varied to produce ADR (or DMN)/ribonucleotide ratios ranging from 1:16 to 2:1. Poly (A-U), ADR and DMN were not efficacious antiviral agents when tested individually at the concentrations employed in the ADR (or DMN)/poly (A-U) combinations. When the ADR or DMN was combined with the poly (A-U) to produce ADR (or DMN)/poly (A-U) ratios of 1/6, the 50% effective doses (ED50) of the poly (A-U), ADR and DMN decreased 18, 104, and 185-fold, respectively. However, when ADR or DMN was combined with polyriboinosinic-polyribocytidylic acid [poly (I) · poly (C)], the ED50 of the ADR, DMN and the poly (I) · poly (C) were not affected. Interferon neutralization studies indicated that ADR, DMN, poly (A-U) and the ADR (or DMN)/poly (A-U) combination induced the production of interferon-beta (IFN-β). The amount of IFN produced by the ADR (or DMN)/poly (A-U) combinations was equal to the sum of the IFN prduced by their constituents. These results indicate that the ADR and DMN potentiate the antiviral activity of the poly (A-U) without affecting the amount of IFN induced. The direct viral inactivation study demonstrated that ADR, DMN, poly (A-U) and the ADR (or DMN)/poly (A-U) combinations do not inactivate the VSV at concentrations near the ED50.