Inducers of interferon and host resistance. I. Double-stranded RNA from extracts of Penicillium funiculosum.

Since interferon' per se shows little promise as a prophylactic or therapeutic agent, interest has shifted to a search for acceptable inducers by which the body might be stimulated to make its own interferon. Shope2 demonstrated that a substance which was derived from Penicilliumfuniculosum and which was called helenine induced resistance to Semliki Forest and to Columbia SK virus infections in mice. Lewis et al.3 fractionated helenine and prepared a factor active in the mouse assay which exhibited properties of a nucleoprotein. Rytel, Shope, and Kilbourne4 demonstrated that helenine elicited a viral inhibitor in cell cultures and in mice which exhibited properties similar to those of interferon. In commenting, they stated that "the active principle in helenine is still a matter of conjecture since it has not been obtained in a sufficiently pure form to permit definite identification." Studies in our laboratories during the past several years have been directed toward the discovery of an interferon inducer which would be worthy of clinical evaluation. It was found that certain ribonucleic acids were highly active in inducing interferon and host resistance but were dependent upon (a) freedom from inhibitory protein and (b) multistrandedness of the RNA. Ribonucleoproteins and single-stranded nucleic acids were inactive. This series of papers describes the purification or synthesis and characterization of three kinds of multistranded RNA active in inducing interferon and host resistance. The present report describes the isolation and characterization of a double-stranded RNA from extracts of Penicillium funiculosum (helenine) which, when freed of protein, is a highly active inducer of interferon and host resistance. The substance is referred to as HeI-RNA. Subsequent papers will present data showing high level interferon and host resistance-inducing activities of multistranded complexes of synthetic polynucleotides5 and of double-stranded RNA of reovirus origin.6