Human papillomaviruses: A window into the mechanism and regulation of eucaryotic cellular DNA replication

Papillomaviruses are ubiquitous pathogens of humans and other vertebrates. Productive infections lead to hyperproliferative lesions in squamous epithelia from diverse anatomic sites, both cutaneous and mucosal. The 7,900 bp double-stranded, circular DNA genome replicates as extrachromosomal plasmids in the nuclei of infected cells. The productive phase of the HPV infection takes place in differentiated, post-mitotic squamous keratinocytes. However, viral DNA replication requires the host cells to supply much of the replication machinery and substrates. Consequently, these viruses usurp the cellular control mechanisms via protein interactions and provide an excellent model system to investigate cellular processes. This paper summarize our investigations and insight into the virus-host interactions observed in productively infected patient lesions, in a model organotypic culture system of primary human keratinocytes transduced with viral genes, and in a cell-free viral DNA replication system with purified viral and host protein.