Transcriptional regulation of early-response genes during polyomavirus infection

Infection of quiescent BALB/c 3T3 cells with polyomavirus leads to the biphasic accumulation of RNA from several early-response genes. The steady-state levels of RNA of c-fos, c-myc, and c-jun were detected at 0 to 1 and 12 to 30 h after infection but not at 6 h postinfection. Infections with mutant viruses suggest that in the context of a virus infection with other tumor (T) antigens present, large T and middle T antigens are dispensable for the effect and small t antigen is important for the regulation, perhaps in conjunction with large T or middle T antigens. These results are in agreement with those of Zullo et al. (Proc. Natl. Acad. Sci. USA 84:1210-1214). We have further found that this regulation occurs in NIH 3T3 cells and primary mouse embryo fibroblasts. DNA synthesis is not required for this effect. Half-lives of c-fos, c-myc, and c-jun were similarly short at both early and late times after infection, as determined by dactinomycin chase. The regulation of expression occurs at the transcriptional level. Nuclear run-on experiments showed increased rates of transcription both early and late after infection. Also, the polyomavirus early region can transactivate the c-fos promoter in transient transfection assays.