Alternative mechanisms for gene activation induced by poly(rI) · poly(rC) and Newcastle disease virus

Abstract

After poly(rI) · poly(rC) induction of FS‐4 fibroblasts, both human interferon‐β (IFN‐β) mRNA and an additional induced RNA class (12S RNA) hybridize to a genomic cosmid clone containing the human IFN‐β gene as well as 35 kbp of flanking sequences. However, this coinduced 12S RNA does not originate from regions in the neighborhood of the IFN‐β gene, but hybridizes to the genomic cosmid clone via repetitive Alu‐family sequences. While IFN‐β mRNA rapidly decays after reaching a maximum 2–4 h after induction, this 12S RNA is stably maintained in the fibroblast cell for more than 16 h. Contrary to IFN‐β mRNA, the level of the 12S RNA is not further elevated by superinduction conditions (cycloheximide treatment) during poly(rI) · poly(rC) induction. However, subsequent to treatment with the weaker viral inducer Newcastle disease virus (NDV) both IFN‐β and the 12S RNA transcripts are induced to a higher level in the presence of cycloheximide. Cell‐free translation of hybrid‐selected 12S RNA leads to detection of an induced protein of 14 kDa. cDNA cloning reveals that the 12S RNA contains part of an Alu‐family sequence in the 5′‐untranslated region. The 12S RNA is probably not an RNA polymerase III transcript and codes for a protein of 9 kDa (as monitored by in vitro cell‐free translation). This discrepancy in molecular mass can be attributed to a retarded migration of the protein in SDS/PAGE.

Footprinting Studies on the Sequence-Selective Binding of Tilorone to DNA

“…response genes whose products induce and maintain the antiviral state. Such an explanation has been advanced to explain the antiviral activity of the double-stranded RNA poly(rl).poly(rC) Which also acts as a potent interferon inducer (Lammers et al, 1988). But because of the poor sequence selectivity of binding of tilorone to DNA we feel that this explanation is probably unrealistic.…”

Synergistic Anti-Human Immunodeficiency Viral (HIV-1) Effect of the Immunomodulator Ampligen (Mismatched Double-Stranded RNA) with Inhibitors of Reverse Transcriptase and HIV-1 Regulatory Proteins

“…The cells were grown in RPMI 1640 medium supplemented with 15% (vlv) fetal calf serum; cultures were maintained at 3rC in a humidified 5% CO2 in air atmosphere (Muller et al, 1988). stomatitis virus system without affecting the interferon production. The authors suggest that the polynucleotide together with the intercalating dyes directly activate the interferon response genes, which are known to maintain the antiviral state (Lammers et al, 1988).…”