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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
and¹ Laboratorie de Biochimie des Protéines, Université de Montpellier, France

The mechanism of interferon resistance was studied in two clones of Daudi cells, DIF₂ and DIF₃, which exhibit respectively moderate and pronounced resistance to both the antiviral and antiproliferative actions of human interferons- and -. Clones DIF₂ and DIF₃ were found to possess specific high affinity interferon receptors similar to those of parental Daudi cells. However, DIF₂ cells, which have a tetraploid karyotype, had approximately twice as many interferon-binding sites as either DIF₃ 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 DIF₂ or DIF₃ cells treated with interferon-. However, neither DIF₂ nor DIF₃ 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 DIF₂ and DIF₃ 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 DIF₂ and DIF₃ was not due to a deficiency of pp(A2' p)_nA.

Keywords: IFN resistance, IFN receptors, cGMP, 2'-5' A synthetase, Daudi cells

Received 7 April 1983; accepted 25 August 1983.

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