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Journal of Virology, May 2006, p. 4431-4439, Vol. 80, No. 9
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.9.4431-4439.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Different Modes of Human Papillomavirus DNA Replication during Maintenance

Ralf Hoffmann,1 Bernhard Hirt,2 Viviane Bechtold,1 Peter Beard,2 and Kenneth Raj1*

National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom,1 Swiss Institute for Experimental Cancer Research, 1066-Epalinges, Switzerland2

Received 11 November 2005/ Accepted 10 February 2006

Human papillomavirus (HPV) begins its life cycle by infecting the basal cells of the epithelium. Within these proliferating cells, the viral genomes are replicated, maintained, and passed on to the daughter cells. Using HPV episome-containing cell lines that were derived from naturally infected cervical tissues, we investigated the mode by which the viral DNAs replicate in these cells. We observed that, whereas HPV16 DNA replicated in an ordered once-per-S-phase manner in W12 cells, HPV31 DNA replicated via a random-choice mechanism in CIN612 cells. However, when HPV16 and HPV31 DNAs were separately introduced into an alternate keratinocyte cell line NIKS, they both replicated randomly. This indicates that HPV DNA is inherently capable of replicating by either random-choice or once-per-S-phase mechanisms and that the mode of HPV DNA replication is dependent on the cells that harbor the viral episome. High expression of the viral replication protein E1 in W12 cells converted HPV16 DNA replication to random-choice replication and, as such, it appears that the mode of HPV DNA replication in proliferating cells is dependent on the presence or the increased level of this protein in the host cell. The implications of these observations on maintenance, latency, and persistence are discussed.


* Corresponding author. Mailing address: National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. Phone: 44 20 8816 2191. Fax: 44 20 8906 4477. E-mail: kraj{at}nimr.mrc.ac.uk.


Journal of Virology, May 2006, p. 4431-4439, Vol. 80, No. 9
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.9.4431-4439.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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Copyright © 2006 by the American Society for Microbiology. All rights reserved.