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.
D000227:Adenine Nucleotides / Q000494:pharmacology; D000818:Animals; D001681:Biological Assay; D002460:Cell Line; D006358:Hot Temperature; D007369:Interferon Inducers / Q000494:pharmacology*; D007668:Kidney; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D011063:Poly A-U / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D011072:Poly U / Q000494:pharmacology; D011119:Polynucleotides / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D013942:Thymine Nucleotides / Q000494:pharmacology; D014500:Uracil Nucleotides / Q000494:pharmacology; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects; D010948:Viral Plaque Assay
D000227:Adenine Nucleotides; D007369:Interferon Inducers; D011119:Polynucleotides; D013942:Thymine Nucleotides; D014500:Uracil Nucleotides; D011063:Poly A-U; D011072:Poly U; D011070:Poly I-C