Cellular Mechanisms of Interferon Production

Rabbit kidney cell cultures stimulated with either double-stranded polyinosinate-polycytidylate (poly I:poly C) or with ultraviolet-irradiated Newcastle disease virus (UV-NDV) produce two types of interferon response, designated "early" and "late," respectively. The early response is suppressed by inhibitors of RNA or protein synthesis and is therefore thought to represent de novo synthesis of interferon. Circumstantial evidence suggested that this interferon response is regulated by a translation control mechanism. Late interferon production with poly I:poly C only took place in the presence of inhibitors of RNA or protein synthesis. The late interferon is therefore likely to be derived by the activation of an interferon precursor. The stimulation of late poly I:poly C-induced interferon production by cycloheximide suggested the existence of a second, posttranslational level of control of interferon production. This posttranslation control seems to be activated by interferon. UV-NDV can probably suppress the synthesis of the posttranslation inhibitory protein, and therefore it stimulates a late interferon response in the absence of inhibitors of RNA or protein synthesis. It is postulated that both the translation and posttranslation inhibitor participate in the development of a cellular refractory state to repeated interferon stimulation. The picture of interferon which emerges from this study is one of a heterogenous class of proteins whose production is controlled by cellular repressors acting at various levels.