Isolation of Daudi cells with reduced sensitivity to interferon. II. On the mechanisms of resistance.

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-alpha and -beta. 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-alpha. However, neither DIF2 nor DIF3 cells respond to sodium azide, a nonphysiological 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.