Studies on the antiviral activity and cell interaction of synthetic double-stranded polyribo- and polydeoxyribonucleotides

Abstract

A variety of (radiolabeled) RNA and DNA polymers, including (poly rA)·(poly rU), poly r(A-U), (poly rI)·(poly rC), poly r(I-C), (poly dA)·(poly dT), poly d(A-T), (poly dI)·(poly dC), and poly d(I-C), were compared in their antiviral activity as measured in terms of inhibition of virus plaque formation by vesicular stomatitis virus in human skin fibroblasts. These polymers were also studied with respect to the kinetics of their binding to cells and with respect to their persistence at the outer cell membrane. The kinetics of cell binding was monitored by the loss of acid-insoluble radioactivity from the supernatant fluid; persistence of the polymer at the cell surface was determined by measuring the amount of cell-bound radioactivity that was released upon nuclease treatment. Although preincubation of the polymer at 37° increased the antiviral activity and rate of cell binding, and persistence at the cell surface of each individual polymer, there was no direct correlation between antiviral activity, rate of cell binding, and persistence at the cell surface with all polymers studied. These findings suggest that the differences in antiviral activity among polyribo- and polydeoxyribonucleotides are not related to differences in kinetics of cell binding or persistence of polymer at the cell surface, but reflect an as yet undefined interaction of the polymer with the cell.