Analysis of nonpermissivity in mouse cells overexpressing simian virus 40 T antigen

To analyze the nature of the nonpermissivity of mouse cells for simian virus 40 (SV40) DNA replication, we isolated mouse cells producing SV40 T antigen (Tag) at levels equal to or greater than that found in COS1 cells. These mouse cells were nonpermissive for the replication of exogenously added SV40 DNA, although purified Tag isolated from these cells was able to support SV40 DNA replication in vitro. Furthermore, when mouse cells expressing Tag were fused to monkey cells, SV40 DNA replication was observed. These results indicate that the mere production of large quantities of wild-type SV40 Tag does not overcome the block of nonpermissivity in mouse cells and that cellular factors must play a critical role.