Different kinetics of antiviral and anticellular activities between human recombinant and natural interferon-gamma arising from different receptor-binding properties.
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.
D015088:2',5'-Oligoadenylate Synthetase / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004274:DNA, Recombinant; D004790:Enzyme Induction / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000378:metabolism; D012845:Sindbis Virus / Q000276:immunology
D004273:DNA, Neoplasm; D004274:DNA, Recombinant; D007370:Interferon Type I; D011971:Receptors, Immunologic; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase