Adenovirus IVa2 protein plays an important role in transcription from the major late promoter in vivo

Adenovirus IVa2 protein is essential and multifunctional, with roles in encapsidation and transcriptional activation of the Major Late Promoter (MLP), but the importance of the transcriptional function to viability has not been assessed. To address this question, viral genomes with multiple nonbinding mutations in the MLP downstream elements DE1 and DE2, alone or in combination with nonbinding mutations in the UPE (USF0), were constructed. The results show that DE1/2 and the UPE are functionally redundant, suggesting an important role of IVa2 protein in the activation of the MLP in vivo. Previously, a virus (vIVa2) expressing a 40-kDa IVa2 isoform was created. Neither the DE1/2 mutations nor the USF0 mutations could be recovered in this genetic background. These results suggest that this 40-kDa isoform can play a role in transcription.