Interference with Cell Viability and Poliovirus Multiplication by Polyinosinic-Polycytidylic Acid

Summary The double-stranded complex of polyinosinic and polycytidylic acids (poly I:C) inhibits the replication of poliovirus in Detroit cells. By a plaque reduction assay a linear relationship was found between the logarithm of the plaque reduction % and the logarithm of the poly I:C concentration, with about 50% inhibition by 0.1 µg./ml. of poly I:C. The maximum hypochromic effect at 233 nm. on complexing of the polynucleotides occurred with 6 volumes of poly I and 4 volumes of poly C from equimolar solutions of the two homopolynucleotides. Gel-filtration of such a complex on Sepharose 4 B separated double and single strands. Of the added poly I 7% remained as single strands at the conditions of maximum hypochromic effect. The poly C was found to have a chain length several times larger than that of poly I. Cell multiplication proceeded at normal rate for 48 hr in a spinner culture with 5 µg./ml. of poly I:C. With 25 µg./ml. no cell multiplication took place within 3 days, and 65% of the cells were dead, whereas in a control culture the cell density doubled and only 15% of cells were dead. Isolation of RNA from the cells 3 hr after addition of the inducer showed about 20% higher incorporation of [14C]uridine-2 into the treated cells. The increase of incorporation was evenly distributed in all RNA bands except for the 32 s RNA band which contained about 60% more 14C than the 32 s RNA of the control.