The direct anti-viral activity of single stranded polyribonucleotides II. The effect of molecular size and the involvement of cellular receptors

We have examined the dependence on molecular size of various singlestranded polynucleotides that protect mice against encephalomyocarditis (e. m. c.) virus infection in the absence of circulating interferon. Sequential treatment of mice with various sizes of poly(I) at 8 h before infection followed by poly(C) at 4 h before infection conferred highly significant protection against e. m. c. virus infection. At 100 μg/mouse of both the polynucleotides significant protection occurred with all the sizes of poly(I) examined but the degree of protection decreased with poly(I) smaller than S20, w of 6.13. In this case a decrease in the size of the poly(C) component lowered the degree of protection. On lowering the polynucleotide doses to 20 μg/mouse, significant protection was achieved only when the poly(I) had an S20, w value equal to or greater than 4.39 and again the degree of protection conferred was related to the size of poly( C). Mixtures of poly(I) and a copolymer containing 5-hydroxycytidylic acid, here designated poly(ho5C) copolymer, also conferred significant protection against infection at 8 h before infection providing that the two components were sufficiently large. We only examined the anti-viral activity of mixtures containing equal masses of poly (I) and the poly(ho5C) copolymer at a dose of 20 μg/mouse of each polynucleotide. With poly(l) of all sizes examined (S20,W between 2.50 and 12.5) significant protection occurred when the poly(ho5C) copolymer had an S20,W value of 8.29 or greater. With poly(ho5C) copolymer preparations of progressively smaller sizes significant protection only occurred with progressively larger sizes of poly(I). These results are considered in relation to other phenomena, including interferon induction by the double stranded complex, poly(I:C), showing dependence on the size of poly(i).