Mechanism of activation of early viral transcription by the adenovirus E1A gene product.

Results obtained with certain adenovirus host range mutants (dl312 and hr1) have demonstrated that a functional viral E1A gene is required for the accumulation of early viral mRNA. In this report, it is demonstrated that the failure to accumulate early viral mRNA in E1A mutant-infected cells is due to a lack of transcription of the appropriate transcription units. The E1A gene product appears to enhance transcription of the early transcription units since there is not an absolute requirement for its function. At low multiplicities of infection, transcription from the early transcription units can be detected but at a later time. By increasing the multiplicity of infection, this show activation of early transcription can be enhanced, even though at this multiplicity all input viruses are still mutant. It was also found that early transcription could be detected in mutant-infected cells if the virus was added to cells in which protein synthesis was inhibited prior to infection. Thus inhibition of cellular protein synthesis can mimic the function of the E1A gene. It is proposed that the role of the E1A gene product in the activation of early viral transcription is to inactivate a cellular factor that prevents transcription from the early viral promoters.