The Continued Presence of Interferon is not Required for Activation of Cells by Interferon

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Abstract
This study was undertaken to help determine whether or not the reaction of interferon with cells which leads to the rapid induction of the antiviral state (a) is initiated by the first binding of interferon to cells and (b) continues to occur after removal of the interferon. Experiments measuring the binding of interferon to cells over 15 min at 0 and 37° and the development of resistance showed that there was no significant difference between the amount of interferon bound to the cells at the two temperatures, but the rate of development of resistance was slowed if the initial binding occurred at 0°. This indicated that cell-bound interferon alone could not account for the rapidly developing resistance since equal amounts of interferon were bound at 0° and 37° but the rates of development of resistance were different. Experiments employing different volumes of medium for elution of interferon bound to cells at 0 or 37° showed that the eluting volume influenced the development of resistance in cells initially exposed to interferon at 0° but not in cells initially exposed at 37°. This indicated that the eluting interferon did not play a role in the rapid development after initial reaction at 37° as it does after initial reaction at 0°. The failure of antibody to inter-feron to prevent the development of resistance after brief reaction of interferon with cells at 37° indicates that the continued presence of cell membrane-bound interferon is not required for development of this resistance. The present findings when taken together with previous findings indicate that a brief temperature-dependent interaction between interferon and human cells initiates one or more cellular processes which no longer requires the presence of interferon and leads 30 min later to the derepression of the cistron which controls the development of the antiviral state.