Russell J K, Blalock J E
Cancer Res. 1985 May;45(5):2098-102.
Vitamin A (retinoic acid, 10(-6) M) treatment of confluent mouse embryo cells for only 7 h resulted in optimal inhibition of Polyomavirus replication. Depending upon the input multiplicity of virus, one could wait until between 12 and 18 h postinfection to add vitamin A and still observe maximal inhibition of virus yields. Taken together, and assuming the same kinetics before and after virus infection, these results suggested that the inhibitory action of vitamin A occurred between 19 and 25 h into the Polyomavirus replication cycle. In this model system, such a time corresponded to the onset of T-antigen expression and virus-induced cellular DNA synthesis. Analysis of both viral and virus-induced cellular DNA synthesis by the method of Hirt (J. Mol. Biol., 26: 365-369, 1967) and by cesium chloride gradients suggested that vitamin A preferentially inhibited viral, more than virus-induced cellular, DNA synthesis in confluent cell monolayers. Vitamin A also concomitantly inhibited Polyomavirus T-antigen expression in such confluent cultures. In contrast, viral DNA synthesis and infectious virus yields were not significantly inhibited by vitamin A in subconfluent cell cultures. The antagonistic effect of vitamin A on Polyomavirus replication in confluent monolayers could be blocked with cycloheximide, a reversible protein synthesis inhibitor. This suggested that vitamin A inhibition of Polyomavirus replication was indirect and mediated by a newly synthesized protein. Taken together, these results suggest that vitamin A induced a protein in confluent, but not subconfluent, cells, which blocked the expression of Polyomavirus T-antigen. Decreased amounts of T-antigen most likely reduced Polyomavirus and cellular DNA synthesis and virus yield.
用维生素A（视黄酸，10⁻⁶ M）处理汇合的小鼠胚胎细胞仅7小时，即可对多瘤病毒复制产生最佳抑制作用。根据病毒的输入复数，可在感染后12至18小时之间添加维生素A，仍可观察到对病毒产量的最大抑制。综合考虑，并假设病毒感染前后的动力学相同，这些结果表明维生素A的抑制作用发生在多瘤病毒复制周期的19至25小时之间。在该模型系统中，这样的时间对应于T抗原表达和病毒诱导的细胞DNA合成的开始。通过Hirt方法（《分子生物学杂志》，26: 365 - 369, 1967）以及氯化铯梯度对病毒和病毒诱导的细胞DNA合成进行分析，结果表明维生素A在汇合的细胞单层中优先抑制病毒DNA合成，而非病毒诱导的细胞DNA合成。维生素A在这种汇合培养物中还同时抑制了多瘤病毒T抗原的表达。相比之下，在亚汇合细胞培养物中，维生素A对病毒DNA合成和感染性病毒产量没有显著抑制作用。维生素A对汇合单层中多瘤病毒复制的拮抗作用可被环己酰亚胺（一种可逆的蛋白质合成抑制剂）阻断。这表明维生素A对多瘤病毒复制的抑制是间接的，由一种新合成的蛋白质介导。综合这些结果表明，维生素A在汇合而非亚汇合的细胞中诱导产生一种蛋白质，该蛋白质阻断了多瘤病毒T抗原的表达。T抗原量的减少很可能降低了多瘤病毒和细胞DNA合成以及病毒产量。
