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Journal of Virology, November 2009, p. 11784-11794, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01370-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Human Papillomavirus (HPV) Type 18 Induces Extended Growth in Primary Human Cervical, Tonsillar, or Foreskin Keratinocytes More Effectively than Other High-Risk Mucosal HPVs{triangledown}

Michael J. Lace,1,2* James R. Anson,1 Aloysius J. Klingelhutz,3 John H. Lee,4 Aaron D. Bossler,2 Thomas H. Haugen,1,2 and Lubomir P. Turek1,2

Veterans Affairs Medical Center, 601 Highway 6 West, Iowa City, Iowa 52246,1 Department of Pathology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242,2 Department of Microbiology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52244,3 Department of Otolaryngology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 522444

Received 3 July 2009/ Accepted 28 August 2009

Mucosal high-risk (HR) human papillomaviruses (HPVs) that cause cervical and other anogenital cancers also are found in ~25% of head and neck carcinomas (HNCs), especially those arising in the oropharynx and the tonsils. While many HR HPV types are common in anogenital cancer, over 90% of HPV-positive HNCs harbor HPV type 16 (HPV-16). Using a quantitative colony-forming assay, we compared the ability of full-length mucosal HPV genomes, i.e., the low-risk HPV-11 and HR HPV-16, -18, and -31, to persist in and alter the growth of primary human keratinocytes from the foreskin, cervix, and tonsils. The HR HPV types led to the formation of growing keratinocyte colonies in culture independent of the site of epithelial origin. However, HPV-18 induced colony growth in all keratinocytes >4-fold more effectively than HPV-16 or HPV-31 and >20-fold more efficiently than HPV-11 or controls. HPV-11-transfected or control colonies failed to expand beyond 32 to 36 population doublings postexplantation. In contrast, individual HR HPV-transfected clones exhibited no apparent slowdown of growth or "crisis," and many maintained HPV plasmid persistence beyond 60 population doublings. Keratinocyte clones harboring extrachromosomal HR HPV genomes had shorter population doubling times and formed dysplastic stratified epithelia in organotypic raft cultures, mirroring the pathological features of higher-grade intraepithelial lesions, yet did not exhibit chromosomal instability. We conclude that, in culture, the HR HPV type, rather than the site of epithelial origin of the cells, determines the efficacy of inducing continued growth of individual keratinocytes, with HPV-18 being the most aggressive mucosal HR HPV type tested.

* Corresponding author. Mailing address: Veterans Affairs Medical Center, 601 Highway 6 West, Iowa City, IA 52246. Phone: (319) 338-0581, ext. 7504. Fax: (319) 339-7179. E-mail: michael-lace{at}uiowa.edu

{triangledown} Published ahead of print on 9 September 2009.

Journal of Virology, November 2009, p. 11784-11794, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01370-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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