Polyinosinic acid

Interferon is a low molecular weight protein, produced by vims-infected cells, that itself induces the formation of a second protein inhibiting the transcriphon of viral mRNA. Interferon is produced by the host cell in response to the vims particle, the viral nucleic and non-viral agents, including synthetic polynucleides such as polyinosinic acid polycytidylic acid (poly I C). There are two types of interferon. 

Lysine-rich proteinoids preferentially interact to form microparticles with polycytidylic acid and polyuridylic acid. On the other hand arginine-rich proteinoids interacts much more readily with polyguanylic acid and polyinosinic acid to form such particles under the same condition57>. Lysine-rich proteinoids had most often shown a preferential precipitation with polyuridylic acid in the experiments for interaction between polynucleotides and the proteinoids in the presence of Mg2+ 56). 

Figure 22 represents the depolymerization by zinc ions of RNA molecules and other polyribonucleotides, in which all of the bases are the same—i.e., polyadenylic, polycytidylic, polyuridylic, and polyinosinic acid 12). Notice that the rates of degradation, or depolymerization, are not the same. The ability of the metal ion to cleave a phosphodiester linkage seems to depend on the nature of the base adjacent to that linkage. 

Synthetic polynucleotide complexes have been shown to be effective immune response modulators in animals and man (Braun et al. 1971, Johnson 1979). The polynucleotides are formed foUowing the action of an enzyme, polynucleotide phosphor-ylase on the synthetic mononucleotide diphosphates. Complexing takes place following the mixing of polymers composed of opposite base pairs. Two have been utilised, polyinosinic acid complexed with polycytidylic acid (poly I poly C) and polyad-enylic acid complexed with polyuridylic acid (poly A poly U). The single strands mononucleotides are ineffective. 

Theoretically, it may be possible to artificially increase the production of interferon by the action of an inducer. Synthetic double-stranded ribonucleotide polymers, in particular the double-helical complex of polyinosinic acid with poly-cytidylic acid RNA (poly IC) are used in this way These agents activate the synthesis of interferon. They increase the resistance to viruses of cells m culture, and promote recovery in rabbits suffering from herpetic eye infection. This type of activity is an important prospect in the field of antiviral therapy. 

Fig. 8. A view down the helix axis of four stranded polyguanylic acid. Polyinosinic acid has the same...

Fig. 9. Calculated and observed CD for polyinosinic acid. The calculated curves used either the Ar-nott et al [20] coordinates for the bases or the Zimmerman et al [21] coordinates. (Reprinted from C.L. Cech and 1. Tinoco, Jr. Nucleic Acids Research.)...

Anari MR, Cribb AE and Renton KW (1995). The duration of induction and species influences the downregulation of cytochrome P450 by the interferon inducer polyinosinic acid-polycytidylic acid. Drug Metabolism and Disposition, 23 536-41. 

Bleaney, R. C., Jones, A. S., and Walker R. T. (1975) Synthetic analogs of polynucleotides XIV. The synthesis of poly-(3 -0-carboxylmethyl-2 -deoxycytidine), and its interaction with polyinosinic acid. Nucl Acids Res 2, 699-706. 

Davies, D. R., Rich, A. The formation of a helical complex between polyinosinic acid and polycytidylic acid. J. Amer. chem. Soc. 80, 1003-1004 (1958). 

Replication of various viruses in cells may also be inhibited by exposure of cells to interferon. Interferon is a glycoprotein formed by cells themselves when they are exposed to specific inducers. The most effective synthetic inducers of interferon are found between nucleic acids and polynucleotides. Electroneutral polyvinyl analogs of nucleic acids are incapable of inducing interferon in cells in culture (10). On the other hand, the complex of polyvinyl-l-cytosine with a polynucleotide, polyinosinic acid, is a very effective inducer of interferon (11). A principal reason for this effectiveness may be a high uptake of this complex by cells (10). 

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