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Journal of Virology, May 2005, p. 5914-5922, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.5914-5922.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Variant Upstream Regulatory Region Sequences Differentially Regulate Human Papillomavirus Type 16 DNA Replication throughout the Viral Life Cycle

Walter G. Hubert*

Department of Dermatology, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, Arkansas 72205

Received 11 October 2004/ Accepted 8 January 2005

While the central role of the viral upstream regulatory region (URR) in the human papillomavirus (HPV) life cycle has been well established, its effects on viral replication factor expression and plasmid replication of HPV type 16 (HPV16) remain unclear. Some nonprototypic variants of HPV16 contain altered URR sequences and are considered to increase the oncogenic risk of infections. To determine the relationship between viral replication and variant URRs, hybrid viral genomes were constructed with the replication-competent HPV16 prototype W12 and analyzed in assays which recapitulate the different phases of normal viral replication. The establishment efficiencies of hybrid HPV16 genomes differed about 20-fold among European prototypes and variants from Africa and America. Generally, European and African genomes exhibited the lowest replication efficiencies. The high replication levels observed with American variants were primarily attributable to their efficient expression of the replication factors E1 and E2. The maintenance levels of these viral genomes varied about fivefold, which correlated with their respective establishment phenotypes and published P97 activities. Vegetative DNA amplification could also be observed with replicating HPV16 genomes. These results indicate that efficient E1/E2 expression and elevated plasmid replication levels during the persistent stage of infection may comprise a risk factor in HPV16-mediated oncogenesis.


* Mailing address: Department of Dermatology, MS576, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205. Phone: (501) 686-5110. Fax: (501) 686-7264. E-mail: wghubert{at}uams.edu.


Journal of Virology, May 2005, p. 5914-5922, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.5914-5922.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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