Initiation and maintenance of cell transformation by simian virus 40: a viral genetic property.

Abstract

The transforming ability in 10% serum medium of the temperature-sensitive mutants of simian virus 40 in the complementation group III (ts640 type mutants) was greatly reduced when the infected rat 3Y1 cells were incubated at the restrictive temperature of 400 or incubated first at 40°for 3 days and then shifted to the permissive temperature of 33°. Transformation did occur efficiently after incubation at 330 or after an initial incubation at 330 for 5 days followed by a shift to 400. When growth properties of 3Y1 cells transformed at 330 by the group III mutants were examined at 40°, several aspects of the transformed state were rendered temperature-sensitive. These aspects were the ability of cells to grow in low serum (1.5%) medium and to make colonies, in 10% serum medium, on monolayers of untransformed 3Y1 cells and in soft agar. It is concluded that a simian virus 40 gene (cistron III) controls the initiation, as well as at least some aspects of the maintenance, of transformation and that the initiation reaction is a more heat-labile event than the maintenance reaction(s) under the experimental conditions.

Recombinant retroviruses encoding simian virus 40 large T antigen and polyomavirus large and middle T antigens.

“…6C) 70). Subsequently, use of conditional or deletion mutants and cloned DNA fragments demonstrated that both of the T antigens encoded by the early region were necessary and sufficient for transformation (10,29,70 (22,39,60,65,70 45,53,59,70). This difference between the type A and N transformants may be attributable to a partial stabilization of the newly synthesized large T antigen in the A-type transformants at the nonpermissive temperature (22).…”

“…Extensive work has shown that genes encoded by the early regions of these viruses are both necessary and sufficient for transformation (1,10,12,14,15,18,29,38,43,49,67; for a review see reference 70). Analysis of the respective roles of these genes has been complicated because the early regions are multiply spliced to specify more than one protein: Py encodes three antigens, the large T (100 kilodaltons [kDa]), the middle T (56 kDa), and the small T (22 kDa) (20,21,24,25,58); SV40 encodes two antigens, the large T (95 kDa) and the small T (20 kDa) (48,51,69).…”

Phenotypic Characterization of Adenovirus Type 12 Temperature‐Sensitive Mutants in Productive Infection and Transformation

“…It is then clear that cell transformation by Ad12 consists of at least two events, initiation and maintenance. A similar situation has been reported for cell transformation by other small DNA containing viruses, SV40 (17) and polyoma virus (6,14), by using DNA-negative ts mutants.…”

“…Since clonal cultures of 3Y1 cells were used for the parental cells, the temperaturedependent properties of the ts505-transformed cells do not appear to be due to the accidental isolation of ts cells which might have existed in the original cell population. That a viral ts mutation can influence the properties of transformed cells has been shown for SV40 (1,17,24,25,31) and polyoma virus (10,14).…”

“…Untransformed 3Y1 cells grow well in medium containing a high concentration (10%) of serum but less well in a low (2%) serum concentration (14,17), whereas 3Y1 cells transformed by polyoma virus (14), simian virus 40 (17), or Ad12 (13) grow well in both low and high concentrations of serum. Six independently transformed ts505-3Y1 lines were tested for their ability to grow in 2% serum (and 10% for some lines) at 40.5 C and 37 C, together with four WT(Ad)-transformed 3Y1 lines and the parental 3Y1 cells.…”