The direct anti-viral activity of single stranded polyribonucleotides I. Potentiation of activity by mixtures of polymers which do not anneal

Mixtures containing equal masses of polyinosinic acid (poly (I)) and copoly­mers containing poly(5-hydroxycytidylic acid), (poly(ho5C) copolymers), protect mice against encephalomyocarditis (e. m. c.) virus infection and the protective effect is greatest 6 h before infection. The batches of poly(ho5C) copolymer used in these studies were obtained by bromine water treat­ ment of polycytidylic acid (poly(C)) and contained cytidine, bromocytidine and hydroxycytidine residues with the latter component comprising between 50% and 81% of the total residues in different preparations. These copolymers were used in solution or in a gelled form obtained by freezing in the absence of salt. Evidence is presented which shows that double stranded complexes do not form when the poly(ho5C) copolymers are mixed with poly(I). Protection of mice with mixtures of poly(I) and poly(ho5C) copolymer was slightly greater than had previously been observed with sequential administration of poly(I) followed by poly(C) or the homopolymer form of poly(ho5C). The gelled form of poly(ho5C) copolymer conferred slightly greater protection than poly(ho5C) copolymer used in the soluble state. The percentage of hydroxycytidine residues in the copolymers did not affect the degree of protection conferred by mixtures of the copolymers with poly (I). Administration of mixtures of poly(I) and soluble poly (ho5C) copoly­mer by the intraperitoneal route was more effective than the intravenous route when high doses were used at 6 h before infection. At this time, 200 μg/mouse of a mixture of poly (I) and poly(ho5C) copolymer was as protec­tive as 60μg/mouse poly(I:C) but the toxicity of mixtures of poly(I) and poly(ho5C) was less than one tenth that of poly(I:C). The mechanism of the protective effect with single stranded polynucleo­ tides cannot yet be stated with confidence. However, the protection by mixtures of poly(I) and poly(ho6C) copolymer does not seem to be through interferon production. Serum from mice treated with the nurture of polynucleotides cannot confer protection on other mice subsequently exposed to infection. Further, the mixtures do not hypo-reactivate the protective effect of poly (I : C) treatment which would have been expected had both effects had a common basis in the interferon phenomenon. Moreover, treatment with the mixture does not result in a stimulation of immune response produced by e. m. c. virus infection.