Isolation of Daudi Cells with Reduced Sensitivity to Interferon. II. On The Mechanisms of Resistance

Laboratoire d'Oncologie Virale, Institut de Recherches Scientifiques sur le Cancer, 94802 Villejuif Cedex and 1 Laboratorie de Biochimie des Protéines, Université de Montpellier, France The mechanism of interferon resistance was studied in two clones of Daudi cells, DIF 2 and DIF 3 , which exhibit respectively moderate and pronounced resistance to both the antiviral and antiproliferative actions of human interferons- and - . Clones DIF 2 and DIF 3 were found to possess specific high affinity interferon receptors similar to those of parental Daudi cells. However, DIF 2 cells, which have a tetraploid karyotype, had approximately twice as many interferon-binding sites as either DIF 3 or parental Daudi cells. One of the first detectable changes in Daudi cells following interferon treatment is a rapid increase in the intracellular concentration of cyclic GMP. No increase in cyclic GMP was observed in DIF 2 or DIF 3 cells treated with interferon- . However, neither DIF 2 nor DIF 3 cells respond to sodium azide, a non-physiological inducer of cyclic GMP. Interferon treatment was found to induce the production of 2'-5'-oligo-isoadenylate synthetase in DIF 2 and DIF 3 cells in a manner similar to parental Daudi cells, indicating that these cells possess functional interferon receptors. The levels of 2'-5'-oligo-isoadenylate synthetase and 2'-5' A phosphodiesterase activity were similar in all three cell lines, suggesting that the interferon resistance of clones DIF 2 and DIF 3 was not due to a deficiency of pp(A2' p) n A. Keywords: IFN resistance, IFN receptors, cGMP, 2'-5' A synthetase, Daudi cells Received 7 April 1983; accepted 25 August 1983.