Interferons-alpha/beta- and -gamma-resistant Friend cell variants exhibiting receptor sites for interferons but no induction of 2-5A synthetase and 67K protein kinase.
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.
Coccia
E M
EM
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Federico
M
M
Romeo
G
G
Affabris
E
E
Cofano
F
F
Rossi
G B
GB
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D004351:Drug Resistance; D004790:Enzyme Induction / Q000187:drug effects; D005622:Friend murine leukemia virus; D005786:Gene Expression Regulation / Q000187:drug effects; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007942:Leukemia, Experimental / Q000473:pathology*; D051379:Mice; D011494:Protein Kinases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000502:physiology*; D017471:Receptors, Interferon; D014407:Tumor Cells, Cultured; D014762:Viral Interference
D007370:Interferon Type I; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D007371:Interferon-gamma; D011494:Protein Kinases; D015088:2',5'-Oligoadenylate Synthetase