Interferons-α/β- and -γ-Resistant Friend Cell Variants Exhibiting Receptor Sites for Interferons but No Induction of 2-5A Synthetase and 67K Protein Kinase

Abstract

A number of Friend leukemia cell variants with a interferon-γ (IFN-γ)-resistant phenotype have been isolated. They appear resistant to the antiproliferative action of IEN-γ and to the induction of the antiviral state assessed by Friend leukemia virus release and vesicular stomatitis virus yield. Selection was performed via a prolonged exposure to increasing amounts of highly purified recombinant IFN-γ of wild-type Friend cells or of variant clones thereof already resistant to IFN-α/β (Affabris et al., 1982, Virology 120, 441-452). Only the clones derived from IFN-α/β-resistant variants showed a phenotype fully resistant to IFN-γ treatment while keeping their previously acquired resistance to IFN-α/β. These cells are not deficient in high-affinity receptors for IFN-γ so that their resistant phenotype appears to be mediated by events distal to binding of IFN-γ to its receptors. Furthermore, analysis of IFN-induced dsRNA-dependent 2-5A synthetase and 67K protein kinase enzymatic activities, biochemical markers for cellular responses to IFN, showed that both these activities were not induced in IFN-α/β and IFN-γ-resistant clones when treated with either type of IFN. Accordingly, no increased expression of 2-5A synthetase mRNA(s) could be detected by probing poly(A)⁺-enriched RNA from cells exposed to IFN-α/β or IFN-γ treatment with murine or human specific cDNAs. On the other hand, no major changes in restriction patterns of 2-5A synthetase gene(s) were observed in these variant cells by restriction endonuclease digestion and Southern blotting. In addition, analysis of 2-5A synthetase mRNA induction, performed on wildtype cells, showed that the kinetic of induction due to IFN-γ treatment is slower than that obtained with IFN-α/β.