Tovey M G, Dron M, Mogensen K E, Lebleu B, Mechti N, Begonlours-Guymarho J
J Gen Virol. 1983 Dec;64 ( Pt 12):2649-53. doi: 10.1099/0022-1317-64-12-2649.
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.
在Daudi细胞的两个克隆DIF2和DIF3中研究了干扰素抗性机制，这两个克隆分别对人α-干扰素和β-干扰素的抗病毒及抗增殖作用表现出中度和显著抗性。发现克隆DIF2和DIF3拥有与亲本Daudi细胞相似的特异性高亲和力干扰素受体。然而，具有四倍体核型的DIF2细胞的干扰素结合位点数量大约是DIF3细胞或亲本Daudi细胞的两倍。干扰素处理后Daudi细胞最早可检测到的变化之一是细胞内环磷酸鸟苷（cGMP）浓度迅速增加。在用α-干扰素处理的DIF2或DIF3细胞中未观察到cGMP增加。然而，DIF2和DIF3细胞均对非生理性cGMP诱导剂叠氮化钠无反应。发现干扰素处理以类似于亲本Daudi细胞的方式诱导DIF2和DIF3细胞产生2'-5'-寡聚异腺苷酸合成酶，表明这些细胞具有功能性干扰素受体。在所有三种细胞系中，2'-5'-寡聚异腺苷酸合成酶水平和2'-5'A磷酸二酯酶活性相似，这表明克隆DIF2和DIF3的干扰素抗性并非由于pp(A2' p)nA缺乏所致。
