Two mechanisms contribute to the superinduction of poly(I)·poly(C)-induced human fibroblast interferon production

The cumulative interferon yield from cultures of poly(I)·poly(C)-induced human diploid fibroblasts (FS-4) in the first 24 hr after induction is increased (superinduced) approximately 50-fold by appropriate treatment with 5,6-dichloro-1-β- d -ribofuranosylbenzimidazole (DRB) and cycloheximide. Two components have been defined in the biochemical mechanism of this paradoxical enhancement. The content of polyadenylated interferon mRNA in induced and superinduced FS-4 cells was assayed by translation in oocytes in Xenopus laevis. First, as reported earlier (P. B. Sehgal, D. S. Lyles, and I. Tamm, Virology 89, 186–198, 1978), interferon mRNA is approximately 14-fold more stable in the continuous presence of DRB (40 μ M ) than in inhibitor-free controls. Second, estimates of the content of interferon mRNA during the first 3 hr of induction in control cultures and in those exposed to DRB alone or cycloheximide alone are consistent with a 3- to 4-fold higher apparent rate of synthesis of interferon mRNA in treated cultures than would be expected if cycloheximide had no effect on transcription and DRB (40 AM) inhibited transcription ∼80% (P. B. Sehgal, I. Tamm, and J. Vilbek, Virology, 70, 256–259; 542–544, 1976).