We previously demonstrated that the efficiency of cell transformation by simian virus 40 (SV40) is reduced when proliferating rat 3Y1 cells are inoculated with SV40 as compared with when density-arrested cells are inoculated. In this study, we characterized in more detail the cellular state at the time of virus inoculation that affects the susceptibility to SV40 transformation. When density-arrested 3Y1 cells were stimulated to progress one round of cell cycle by refeeding with medium containing high serum, they began to reduce the susceptibility to SV40 transformation before entering S phase. After re-entry into the non-proliferative state, prolonged maintenance of cells in the non-proliferative state was necessary for restoration of the susceptibility to SV40 transformation. Such dependency of the transformation efficiency on the cellular state at the time of SV40 inoculation paralleled with that of the expression of T antigen in nuclei, while virus adsorption and degradation of the DNA of the adsorbed virus was not dependent on the cellular state. We conclude that after inoculation of proliferating cells with SV40, an unidentified event between the virus adsorption and the accumulation of T antigen protein in nuclei is blocked and that this blockage causes the inhibition of the initiation of transformation.

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