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

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Abstract
A number of Friend leukemia cell variants with a interferon-.gamma. (IFN-.gamma.)-resistant phenotype have been isolated. They appear resistant to the antiproliferative action of IFN-.gamma. 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-.gamma. of wild-type Friend cells or of variant clones thereof already resistant to IFN-.alpha./.beta. (Affabris et al., 1982, Virology 120, 441-452). Only the clones derived from IFN-.alpha./.beta.-resistant variants showed a phenotype fully resistant to IFN-.gamma. treatment while keeping their previously acquired resistance to IFN-.alpha./.beta.. These cells are not deficient in high-affinity receptors for IFN-.gamma. so that their resistant phenotype appears to be mediated by events distal to binding of IFN-.gamma. 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-.alpha./.beta. and IFN-.gamma.-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-.alpha./.beta. or IFN-.gamma. 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 wild-type cells, showed that the kinetic of induction due to IFN-.gamma. treatment is slower than that obtained with IFN-.alpha./.beta.