Abstract

The antiviral activities and/or interferon-inducing abilities of poly(I)·poly(C), poly(I)·poly(br⁵C), poly(c⁷I)·poly(C), and poly(c⁷I)·poly(br⁵C) have been assessed in a variety of cell cultures (human, rabbit, and mouse) and animals (rabbits, mice). In cultured cells the compounds were also examined for inhibition of host cell macromolecule synthesis. Lethal effects were looked for in mice sensitized with lead acetate. Although the extent of antiviral activity of the polymers varied from one assay system to another, the following order of (decreasing) activity appeared applicable to all systems: poly(I)·poly(br⁵C) [unknown] poly(I)·poly(C) > poly(c⁷I)·poly(b⁵C) [unknown] poly(c⁷I)·poly(C). Poly(I)·poly(C) and poly(I)·poly(br⁵C) did not differ markedly in antiviral activity, interferon-inducing ability, or toxicity. However, in human skin fibroblasts, poly(I)·poly(br⁵C) was distinctly superior as an interferon inducer, especially at lower doses. Poly(c⁷I)·poly(C) was the least active of the four polymers and was also the most potent inhibitor of host cell macromolecule synthesis. Poly(c⁷I)·poly(br⁵C) equaled or even surpassed poly(I)·poly(C) in interferon-inducing activity in human skin fibroblasts; in animals, however, it proved definitely less active. In determining the antiviral behavior of the complexes studied, two effector mechanisms should be taken into account: interferon induction and inhibition of macromolecule biosynthesis. Which of these parameters will predominate would ultimately depend on the fate of the double-stranded complex after it has reacted with the cell.