Interferon Induction by Synthetic Polynucleotides: Importance of Purine N-7 and Strandwise Rearrangement

The antiviral activity and interferon-inducing ability of single-, double-, and triple-stranded polynucleotides, modified at pyrimidine C-5 or purine N-7, were evaluated in primary rabbit kidney cells challenged with vesicular stomatitis virus. (1 ) There is a parallel increase in antiviral activity and the temperature at which double-stranded polynucleotides rearrange to inactive triple-stranded complexes. (2 ) When the purine N-7 of (A)n is replaced by CH, all resulting double-stranded complexes fail to provide antiviral protection or to induce interferon, even though such complexes meet all requirements previously recognized for interferon induction. (3 ) Competition experiments between inactive and active polynucleotides indicate that single-stranded polynucleotides apparently do not bind to the cellular receptor sites for interferon induction, whereas triple-stranded complexes and inactive double-stranded complexes bind to such receptor sites but, probably for conformational reasons, fail to trigger the necessary message for interferon induction.