A pVII positioning code determines the dynamics of Adenoviral nucleoprotein structure and primes it for early gene activation

Abstract

SUMMARYInside the capsid adenovirus DNA is associated with the structural protein pVII. However, the viral DNA organisation, pVII positioning and the dynamic changes of viral packaging upon infection, to form a transcriptional active genome, are not known. We combined MNase-Seq and single genome imaging during early infection to provide the structure and time resolved dynamics of viral chromatin changes, correlated with gene transcription. pVII complexes form nucleosome-like arrays, being precisely positioned on DNA, creating a defined and unique adenoviral nucleoprotein-architecture. The structure renders the viral genome transcription competent with lower pVII densities at early gene loci, correlating with viral chromatin de-condensation upon infection. Nucleosomes specifically replace pVII at transcription start sites of early genes, preceding transcriptional activation. Our study suggests an underlying regulatory pVII nucleoprotein-architecture, required for the dynamic changes during early infection, including transcription related nucleosome assembly. We suggest that our study provides a basis for the development of recombinant adenoviral vectors exhibiting sustained expression in gene therapy.