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


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