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  • Title: Control of Polyomavirus T-antigen and DNA synthesis in mouse embryo fibroblast cells by vitamin A.
    Author: Russell JK, Blalock JE.
    Journal: Cancer Res; 1985 May; 45(5):2098-102. PubMed ID: 2985244.
    Abstract:
    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.
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