Mechanisms and Regulation of Papillomavirus DNA Replication
Louise T. Chow and Thomas R. Broker
from: Papillomavirus Research: From Natural History To Vaccines and Beyond (Edited by: M. Saveria Campo). Caister Academic Press, U.K. (2006)
Human and animal papillomaviruses each contain a double-stranded circular DNA genome of approximately 7,400 to 8,200 base pairs which replicates as multicopy, extrachromosomal plasmids in the nucleus of infected keratinocytes. To initiate DNA synthesis from the origin of replication (ori), papillomaviruses encode an ori recognition protein E2 and a replicative DNA helicase E1. All other replication proteins as well as anabolic systems that synthesize the deoxynucleotide substrates are supplied by the host. In cycling cells, viral DNA replication maintains a steady copy number of viral genomes per cell. In post-mitotic, differentiated keratinocytes the papillomaviruses induce the host cells back into S-phase and viral DNA undergoes multiple rounds of replication for progeny virion production. In this Chapter, we summarize the findings of numerous laboratories on the mechanisms regulating the initiation of papillomaviral DNA replication as well as the maintenance and amplification of viral DNA, as characterized by in vitro assays independent of other viral proteins that are required in the context of the whole genomic sequence in the host tissues read more ...