After a first exposure to single-stranded polyriboinosinic and polyribocytidylic acids, which initiates interferon production, rabbit kidney cultures become refractory for about 3 days to further stimulation with polyriboinosinic and polyribocytidylic acids. However, when polyriboinosinic and polyribocytidylic acids are left in contact with the cells for several days, the interferon response is not restored to normal, as appears from a gradually decreasing production rate and a decreasing responsiveness to a higher dose. This is interpreted as indicating that refractoriness is not merely due to exhaustion of interferon precursors, but also to a blocking of synthesis of interferon or interferon precursors. Small doses of polyriboinosinic and polyribocytidylic acids which did not induce measurable interferon, but which did stimulate resistance to virus, caused a hyper-reactivity to a second exposure to a high dose of polyriboinosinic and polyribocytidylic acids. It was concluded that in rabbit kidney cells, refractoriness is not correlated with the antiviral state resulting from stimulation of the interferon mechanism.


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