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Regulation of human interferon production stimulated with poly inosinic acid poly cytidylic acid correlation between shutoff and hypo responsiveness to re induction

, : Regulation of human interferon production stimulated with poly inosinic acid poly cytidylic acid correlation between shutoff and hypo responsiveness to re induction. Virology 76(1): 47-54

The exposure of [human fibroblast] FS-4 cells to poly(I).cntdot.poly(C) [2 .mu.g/ml] for 1 h resulted in rapid interferon production which peaked in 3-4 h and was rapidly shut off thereafter, declining to low or undetectable levels by 6 h. Reexposure of cells to 50 .mu.g/ml of poly(I).cntdot.poly(C) at 2, 3, 4 or 5 h after the 1st induction did not prevent the shutoff of interferon production due to the 1st induction. The restimulated cultures underwent a 2nd round of interferon production peaking at 8-10 h. The appearance of the 2nd peak could be inhibited with actinomycin D, if the drug was added 3 h after reexposure to poly(I).cntdot.poly(C), i.e., before the actual onset of the 2nd round of interferon production. The 2nd interferon peak resembled the peak seen after the 1st induction since it also showed a rather steep rise and rapid shutoff. The shutoff of the 2nd peak could be prevented by treatment with actinomycin D at 9 h (5 h after the 2nd stimulation). A 2nd interferon peak at 9 h was also seen following a single 1 h exposure to a high concentration (50 .mu.g/ml) of poly(I).cntdot.poly(C). A rapidly turning over repressor system is apparently induced coordinately with interferon. This repressor system causes irreversible inactivation of interferon mRNA and is likely to be responsible for the shutoff of interferon production and the phenomenon of hyporesponsiveness to repeated interferon induction.

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