Selection against large T-antigen expression in cells transformed by lymphotropic papova virus

Large T-antigen (T-Ag) in hamster cells transformed by the lymphotropic papova virus (LPV) exhibits similar properties as the T-Ag of simian virus 40 (SV40) with regard to its interaction with cellular targets. However, in contrast to SV40-transformed cells, LPV-transformed cells in cell culture select against high expression of LPV T-Ag. Southern analysis revealed that this selection process was accompanied by drastic changes at the DNA level, involving the loss of most of the integrated viral DNA copies. These changes probably were responsible for an approximately 100-fold downregulation of LPV T-Ag transcription. To elucidate the biological significance of this phenomenon, we studied the effects of the expression of LPV and SV40 T-Ag, respectively, in a variety of cells. Our data suggest that LPV T-Ag, like SV40 T-Ag, acts as an immortalizing and transforming protein. However, in contrast to SV40 T-Ag, high-level expression of LPV T-Ag seems to be detrimental to the establishment and maintenance of LPV-transformed cells in vitro.