Kinetics of the Development of Factors Responsible for Interferon-Induced Resistance

Summary and Conclusions

. The present study was performed to help determine the interaction of some of the factors which determine the development and maintenance of the antiviral state in IF-treated mouse embryo (ME) cell culture. Actinomycin D timing experiments were used to estimate the rate of formation of the hypothesized mRNA for the antiviral protein (AVP) of the IF system. Earliest formation is detectable by 1–2 hr and the amount of mRNA required for the production of the maximum resistance at each dose level is synthesized by 5–7 hr. Inhibition by actinomycin D of RNA production at the time of viral challenge of IF-treated ME cells, indicated that no new mRNA for AVP is transcribed and then translated after removal of IF and simultaneous challenge. Arrest of RNA synthesis in ME cells pretreated with IF was followed by an unchanged level of resistance over 6 hr, thereby suggesting that translation of the hypothesized mRNA into AVP is completed very rapidly and that the mRNA is unstable relative to AVP. Removal of IF from cultures in the presence or absence of inhibition of protein synthesis was also followed by an unchanged level of resistance. This finding was interpreted to mean that removal of IF from ME cultures rapidly results in the cessation of production of the hypothesized mRNA for the AVP.