Dynamic chromatin accessibility profiling reveals changes in host genome organization in response to baculovirus infection

DNA viruses can hijack and manipulate the host chromatin state to facilitate their infection. Multiple lines of evidences reveal that DNA virus infection results in the host chromatin relocation, yet there is little known about the effects of viral infection on the architecture of host chromatin. Here, a combination of epigenomic, transcriptomic and biochemical assays were conducted to investigate the temporal dynamics of chromatin accessibility in response to Bombyx mori nucleopolyhedrovirus (BmNPV) infection. The high-quality ATAC-seq data indicated that progressive chromatin remodeling took place following BmNPV infection. Viral infection resulted in a more open chromatin architecture, along with the marginalization of host genome and nucleosome disassembly. Moreover, our results revealed that chromatin accessibility in uninfected cells was regulated by euchromatic modifications, whereas the viral-induced highly accessible chromatin regions were originally associated with facultative heterochromatic modification. Overall, our findings illustrate for the first time the organization and accessibility of host chromatin in BmNPV-infected cells, which lay the foundation for future studies on epigenomic regulation mediated by DNA viruses. Author summary As a well-studied arthropod-specific double-stranded DNA virus, Bombyx mori nucleopolyhedrovirus (BmNPV) is a representative member of baculoviruses. BmNPV infection results in significant host chromatin marginalization, which has also been found in most DNA viruses. However, the effects of baculovirus infection on the organization and accessibility of host chromatin are poorly understood. Here, by using ATAC-seq, we show that DNA virus BmNPV infection gradually remodels the accessibility of host chromatin. ATAC-seq data reveal that the marginalized host chromatin is a more accessible architecture along with the depletion of multi-nucleosome depositions. Moreover, our findings suggest the increased accessibility regions are regulated by the facultative heterochromatic modification. Overall, we provide a novel understanding of molecular mechanisms by which baculovirus and DNA viruses alter the organization of host chromatin in epigenomic regulation.