Antagonism of Non‐Inducer Ribonucleic Acid against Induction of Antiviral Cell Resistance and Interferon by Inducer Ribonucleic Acid

ABSTRACT Various single‐stranded RNAs, which do not induce antiviral cell resistance in L and chick embryo cells, were found to antagonize the action of inducer RNAs such as poly(C)·poly(I). The non‐inducing RNA inhibited production of interferon stimulated by inducer RNA, but did not inhibit the action of exogenously added interferon. Two aspects were discerned in the antagonism of non‐inducing RNA, namely intrinsic antagonism and anti‐protamine effect. The intrinsic antagonism is the one observed in the absence of protamine. The anti‐protamine effect is elimination of the potentiating action of protamine on inducing RNA [10] by non‐inducing RNA in a large excess over protamine. The relative importance of the two effects will vary depending on the concentrations of protamine and non‐inducing RNA used. Non‐inducer RNA added to cells pretreated with inducer RNA for 1–3 hr effectively inhibited the development of antiviral cell resistance, but was not very effective when added prior to inducer RNA. RNA from MS2 phage virions was found to be an inducer in chick embryo cell but a non‐inducer and antagonist in human embryo lung fibroblasts, indicating that a given RNA may possess both the inducer and the antagonist characters. The induction of interferon by viruses was not significantly inhibited by non‐inducing RNA. The results obtained are consistent with an assumption that non‐inducing RNA competitively inhibits the binding of inducer RNA to cellular receptor sites, although alternative interpretations are not excluded.