A
purine analogue,
2-aminopurine, reported to act as an inhibitor of
protein kinase, selectively, reversibly and in a dose-dependent manner blocked a very early stage in
interferon induction. With chick embryo cells and mouse L cells as hosts, and different viral inducers of
interferon, maximal effects of
2-aminopurine were observed during the first 4 h of induction.
At 10 mM-2-aminopurine there was a 20-fold reduction in the yield of
interferon from both cell types.
2-Aminopurine and
actinomycin D both prevented
interferon induction with the same time course, indicating a transcriptional block to induction; however, only the action of the former was reversed upon removal of the
drug. Addition of
2-aminopurine to an
agarose overlay resulted in high efficiency plaque formation by
vesicular stomatitis virus New Jersey (Hazelhurst) under conditions where endogenous induction of
interferon and its feedback action on aged chick embryo cells normally prevented plaque formation. Two other inducible systems, representing genes involved in
interferon action (both its development and activation), and those of heat shock, were not affected by
2-aminopurine. A model is presented implicating the
interferon-inducible dsRNA-dependent
protein kinase as an
interferon induction receptor which, on interaction with dsRNA, generates an amplified signal via phosphorylation that ultimately derepresses the
interferon gene(s).