Hyporeactivity to Interferon Production by Double-Stranded RNA Associated with Hyporeactivity to Antiviral Protection and Hyporeactivity to Toxicity

Mice given repeated injections of either synthetic [poly (I)·poly (C)] or natural (mycophage) double-stranded (ds) RNA developed a marked hyporeactivity in their interferon response to these agents. Two different treatment schedules were used to induce hyporeactivity: (a) repeated injections of poly (I)·poly (C) or mycophage ds-RNA on Days 0, 1, 2 and 4 and (b) two injections of either ds-RNA on days 0 and 4. During the hyporesponsive period mice were significantly less protected against intranasal vesicular stomatitis virus (VSV) challenge, but markedly more tolerant to the lethal effects of the double-stranded RNA. However, repeated injections of the mycophage ds-RNA on Days 0, 1, 2 and 4 brought about a significant decrease of interferon production and toxicity, but no loss of protection against VSV challenge. In all other systems, hyporeactivity to interferon production closely paralleled hyporeactivity to antiviral protection and hyporeactivity to toxicity. The findings presented herein tend to reinforce the interpretation that, in welldefined conditions, these three parameters of the biological activity of double-stranded RNA are interrelated.