Different kinetics of antiviral and anticellular activities between human recombinant and natural interferon-gamma arising from different receptor-binding properties.

Abstract

Human recombinant interferon-gamma (ReIFN-gamma) and human natural interferon-gamma (IFN-gamma) showed significant differences in antiviral and anticellular activities. Namely, ReIFN-gamma exhibited antiviral activity against Sindbis virus and anticellular activity against HeLa S3 cells at significantly lower concentrations as compared with IFN-gamma at short exposure times of between 1 and 4 hr. This difference of activities was explicable in terms of different binding activities of the two IFNs to the receptors. The binding of 125I-ReIFN-gamma to the receptors was competitively decreased in a dose dependent manner by unlabeled ReIFN-gamma, whereas the competition by unlabeled IFN-gamma was significantly weaker. The results of pretreatment of the cells with unlabeled ReIFN-gamma or IFN-gamma suggested that the binding of IFN-gamma to the receptors was slower than that of ReIFN-gamma. ReIFN-gamma and IFN-gamma exhibited greater colony formation-inhibitory activity against HeLa S3 cells, as compared with IFN-alpha or ReIFN-beta. ReIFN-gamma also inhibited DNA, RNA and protein syntheses of HeLa S3 cells more potently than ReIFN-beta. However, the 2'-5' oligoadenylate (2'-5' A) synthetase activity in ReIFN-gamma-treated cells was significantly lower than that in ReIFN-beta-treated cells, suggesting that 2'-5' A synthetase does not play a major role in the anticellular activity of ReIFN-gamma, at least against HeLa S3 cells.