Sokolova T M, Antonov A Iu, Makhov A M
Antibiot Khimioter. 1991 Jun;36(6):31-5.
Novel original preparations of double-stranded RNAs (dsRNAs), i.e. larifan, ridostin and rifastin, and recombinant alpha 2- and beta-interferons promising for the clinical use were studied. The size and morphology of the dsRNAs in the preparation composition, the dynamics of their induction of interferon and the antiviral state in human fibroblasts and the effect of the DEAE dextran polycation on the activity of the dsRNAs were specified. For the first time the dynamics of 2',5'-oligoadenylate synthetase activity in the nuclei and cytoplasm of the human fibroblasts treated with the dsRNAs of different origin and their complexes with DEAE dextran was defined. To elucidate the specific features of the mechanism of antiviral action of dsRNAs and interferon, the relation of the 2',5'-oligoadenylate synthetase activity to dsRNAs was investigated. In the cells treated with dsRNAs and DEAE dextran there were an early activation of the enzyme and predominance of the enzyme activated forms requiring no addition of poly I.poly C to the reaction mixture. The results were indicative of possible intracellular activation of its isoforms, similar to that in the cells treated with interferon and contaminated with viruses. All the tested preparations of dsRNAs and interferons induced an increase in the activity of 2',5'-oligoadenylate synthetase both in the cytoplasm and the nuclei of human fibroblasts. The same ability was observed in DEAE dextran which is likely to be one of the causes of the increase in dsRNAs antiviral activity under its effect.
研究了新型双链RNA(dsRNA)的原始制剂,即拉里凡、利多斯汀和利法斯汀,以及有望用于临床的重组α2和β干扰素。明确了制剂成分中dsRNA的大小和形态、其在人成纤维细胞中诱导干扰素和抗病毒状态的动力学,以及二乙氨基乙基葡聚糖聚阳离子对dsRNA活性的影响。首次确定了用不同来源的dsRNA及其与二乙氨基乙基葡聚糖的复合物处理的人成纤维细胞核和细胞质中2',5'-寡腺苷酸合成酶活性的动力学。为阐明dsRNA和干扰素抗病毒作用机制的具体特征,研究了2',5'-寡腺苷酸合成酶活性与dsRNA的关系。在用dsRNA和二乙氨基乙基葡聚糖处理的细胞中,该酶有早期激活,且在反应混合物中无需添加聚肌苷酸-聚胞苷酸的酶激活形式占优势。结果表明其同工型可能在细胞内被激活,类似于用干扰素处理且感染病毒的细胞。所有测试的dsRNA和干扰素制剂均诱导人成纤维细胞细胞质和细胞核中2',5'-寡腺苷酸合成酶活性增加。在二乙氨基乙基葡聚糖中也观察到同样的能力,这可能是其作用下dsRNA抗病毒活性增加的原因之一。