Cis-acting induction of adenovirus transcription

At early times after adenovirus infection, transcription from all early viral promoters requires the expression of a 289 amino acid phosphoprotein encoded in the pre-early transcription unit E1A. Mutations in E1A result in a marked delay in the induction of early viral transcription. To distinguish between possible models that could account for this delayed transcription, superinfection experiments were performed. Cells were first infected with one E1A mutant, incubated until viral transcription was detectable, and then superinfected with a second E1A mutant with distinguishable transcripts from early region 3 (E3). We found that the second virus to infect the cell recapitulated the delayed transcription induction of E3. Therefore, the delayed expression of early regions after infection with E1A mutants is the result of a time-dependent cis-acting modification of the template. Models which can account for these observations and for the function of E1A protein are discussed.