Requirement of Newly Synthesized Protein for the Priming Activity of Interferon

Abstract

Pretreatment of mouse L cells with interferon (IF) enhanced IF production in response to polyinosinic-polycytidylic acid (poly I.poly C). Post-treatment of cells with IF caused no significant enhancement of IF production. The enhancing effect of IF pretreatment (priming) reached a maximum after incubation with IF (10 or 100 units/ml) for 4-6 hr at 37 C, but this effect was absent \A hen the incubation was done at 4 C. Cells which were incubated for additional several hours at 37 C after IF pretreatment at 4 C did not develop the primed state nor the antiviral state. The presence of protein synthesis inhibitors during the IF pretreatment depressed, though not completely, the development of the primed state. The residual priming effect was lost when the cells were incubated with the inhibitors at 37 C for 2 hr before they were exposed to poly I.poly C. There was no significant difference in the binding rate of poly I.poly C to cells between IF-treated and untreated cells. The degradation rate of cell-bound poly I.poly C and its sensitivity to exogenous pancreatic ribonucicase in the pretreated cells were also similar to those in the untreated cells.Interferon (IF) preparations have been shown to possess various activities other than the antiviral activity. These are inhibition of cell growth [3], enhancement or suppression of IF production [8,10], and enhancement of cytopathic effect of double-stranded RNA [9]. However, it is still unclear whether these activities are ascribable to IF itself or to some other components in IF preparations. It is also unknown whether IF exerts these activities on cells through a common induction mechanism.We previously demonstrated that the priming activity of IF always paralleled the antiviral activity regardless of the source and purity of the IF preparation [4]. The finding suggested that these activities could be ascribed to IF molecules and that there might be some common steps in the development of the primed and antiviral states in IF-treated cells. It has been well known that certain metabolic activities such as RNA and protein syntheses are necessary for developing the antiviral state in cells [5 , 7, 12]. It is, therefore, of interest to determine whether these metabolic processes are also required in the priming process.We report here the effects of temperature, duration of IF treatment and metabolic inhibitors on the priming process in IF-treatied cells and discuss a possible mechanism of the priming action. MATERIALS AND METHODSCells and virus. Mouse L cells were grown in Eagle's minimal essential medium (MEM) supplemented with 5% calf serum (CS) and maintained in MEM supplemented with 2% CS.

Effect of the oral administration of Lactobacillus brevis subsp. coagulans on interferon-alpha producing capacity in humans.

“…As one of the probable causes of the significant increase of IFN-a production, a priming effect [33], a dramatic increase of IFN production by pretreatment with a low dose of IFN followed by stimulation with a virus in vitro, has been reported. 2-5A synthetase is one of the enzymes induced by IFNs [34,35,36].…”

Study of the in vivo Priming Effect of Interferon in Mice

“…This recognition has prompted extensive studies with the aim of elucidating its mechanism of action (Stewart et al, 1971 ;Ito et al, 1975;Roszt6czy 1977;Abreu et al, 1979;Fujita & Kohno, 1981 ;Nir et al, 1985). Though all these studies were conducted under in vitro conditions, priming in vivo may also be important.…”