BmNPV interacts with super-enhancer regions of the host chromatin to hijack cellular transcription machinery.

Effective transcriptional activation relies on the spatial interaction between specific DNA elements. DNA interactions have also been observed between DNA viruses and their hosts, with limited understanding of the involved details. Baculovirus is a representative species of DNA virus and has been reported to interact with the host genome in our previous study. However, the biological significance of the baculovirus-host trans-species DNA interaction and its underlying mechanisms remain elusive. Here, using Bombyx mori nucleopolyhedrovirus (BmNPV) as the model virus, we combine epigenome, transcriptome, and biochemical assays to investigate the baculovirus-host DNA interaction. Our data show that BmNPV hijacks the transcriptional regulatory capacity of host super-enhancers (SEs) by physically interacting with these regions on the host genome. This results in the usurpation of the activating capacity of an SE-binding transcription factor GATA by the virus, thereby impairing the SE-induced specific transcriptional activation of the target antiviral genes. Moreover, the hijacked regulatory capacity is spread on BmNPV genome through cis-interaction of viral DNA, leading to enhanced viral gene expression. Overall, our results provide novel insights into the intricate interplay of viruses with host gene expression regulatory networks and broaden the vision in the mechanisms of viral exploitation on cellular machinery.