Adenovirus E1B-55K alters histone modifications in human cells

Oncogenic viruses can induce epigenetic changes in host cells, which may contribute to cell transformation and tumorigenesis by altering gene expression patterns. Human adenoviruses, while primarily known for their lytic infections, have also been implicated in oncogenic transformation in experimental settings; yet the mechanisms underlying adenovirus oncoprotein-induced epigenetic dysregulation remain poorly defined. Building on our recent findings that the adenoviral oncoprotein E1B-55K coordinates cellular transformation through interactions with DNA-bound host transcription factors, we next sought to determine whether these interactions also influence the chromatin landscape. For this purpose, we investigated the epigenetic consequences of E1B-55K expression in primary human mesenchymal stromal cells using histone-targeting MNase-seq, complemented by RNA-seq analysis. We demonstrate that stable expression of HAdV-C5 E1B-55K leads to widespread changes in histone post-translational modifications across the genome. Most notably, E1B-55K expression results in a marked loss of the activating histone marks H3K4me3 and H3K27ac, particularly at specific promoters and enhancers. These epigenetic alterations correspond with significant changes in gene expression, suggesting that E1B-55K interferes with normal transcriptional programming by altering the establishment of key histone modifications. Our findings aid in revealing the mechanism utilized by E1B-55K in driving viral transformation through epigenetic reprogramming and expanding the current understanding of virus-host interactions at chromatin level. By describing how human adenoviruses disrupt epigenetic homeostasis, we provide insights into the mechanisms by which oncogenic viruses promote early events in cellular transformation.