Role of adenovirus type 2 early region 4 in the early-to-late switch during productive infection.

Deletion of 98% of the adenovirus type 2 E4 transcription unit resulted in a delay of several events characteristic of the intermediate stage of infection, including viral DNA synthesis, induction of the cellular gene coding for dihydrofolate reductase, and the onset of the switch from viral early to late gene expression. Although delayed, both viral DNA replication and dihydrofolate reductase induction eventually approached wild-type levels. Events characteristic of the late stage of infection were both delayed and diminished in mutant-infected cells. Therefore, the viral E4 gene family is involved in the transition from the early to late stages of infection, and events whose timing is coincident or dependent upon the early-to-late switch are delayed.