Lethality in mice of double-stranded ribonucleic acid from virus-like particles of Penicillium stoloniferum.

The LD 50 in mice of intact virus-like particles (VLP) from Penicillium stololllferum NRRL 5267 was greater than 240 mg/kg body weight, and their component double-stranded ribonucleic acid (dsRNA) was 34·0 mg/kg. Judged by decreases in LD50 values, administration of sublethal amounts of actinomycin D or cycloheximide simultaneously with sublethal amounts of intact VLP or mycoviral dsRNA enhanced lethality in mice. A 2400-fold increase in the letahlity of intact VLP occurred in mice treated with actinomycin D and a 65-fold increase with cycloheximide and VLP. Increases in lethality of 850-fold with actinomycin D and 10-fold with cycloheximide were determined when mice were treated simultaneously with either antibiotic and mycoviral dsRNA. Similar lethality effects were observed in mice simultaneously treated with polyriboinosinic-polyribocytidylic acid and either of the antibiotics. Animals treated at zero-time with mycoviral dsRNA and subsequently treated at 1,2,4, 8, and 12 hr with actinomycin D generally exhibited a reduced toxic response after the 4-hr injection with actinomycin D. Animals treated at zero-time with actinomycin D and subsequently with mycoviral dsRNA also exhibited a reduced toxic response after the 4-hr injection with the nucleic acid.