Abstract

Human adenoviruses are tools for gene therapy and vaccination. The viral DNA genome is compacted by protein VII inside the capsid. We show that decompaction of the viral genome and acquisition of host nucleosomes at early promoters enables efficient viral transcriptional activation. Decompaction starts upon maturation, directed by a DNA sequence code, pre-arranging the genome for capsid release and rapid transcriptional activation, highlighting an exceptional example of evolutionary adaptation.