Phenotypic heterogeneity among temperature-sensitive mutants of rous sarcoma virus. Studies with inhibitors of protein synthesis

Abstract

Fourteen temperature-sensitive ( ts), transformation-defective mutants have been isolated from mutagenized Schmidt-Ruppin Rous sarcoma virus. We report that, while in cells infected with most of the mutants all parameters of cell transformation were coordinately suppressed, certain ts mutants induced the ability of infected cells to multiply in soft agarose and to express the tumor-specific surface antigen (TSSA), in the absence of morphological conversion. Studies with inhibitors of protein synthesis have shown that cycloheximide (Ch) and pactamycin (Pac) act differently on focus formation from Pu and that the heat-labile src gene product of these mutants may be spontaneously reactivated following a downshift to permissive temperature. Our data also indicate the existence of two classes of mutants regarding the response of infected cells to Pu. In most cases, focus formation is inhibited by Pu when infected cells are shifted to 37°. However, cells infected with three ts mutants resume morphological transformation at permissive temperature in the presence of this inhibitor. In addition, the fact that the same mutants induce high levels of TSSA expression at restrictive temperatures suggests that the two properties may be linked.