Playing with fire: consequences of human papillomavirus DNA replication adjacent to genetically unstable regions of host chromatin

Papillomaviruses are small DNA viruses that replicate persistently in the stratified epithelial surfaces of the host. They have minimal coding capacity and must hijack many cellular processes to complete their life cycle. For example, viral genomes are tethered to host chromatin to ensure that they are effectively partitioned in dividing cells, and the host DNA damage and repair pathways are usurped to replicate viral DNA in differentiated cells. These processes result in the close juxtaposition of viral DNA with host DNA that is undergoing replication stress. This could explain the propensity of oncogenic human papillomaviruses (HPVs) to accidently integrate into common fragile sites in host DNA.