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Journal of Virology, August 2001, p. 7712-7716, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7712-7716.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Centrosome Abnormalities and Genomic Instability by Episomal Expression of Human Papillomavirus Type 16 in Raft Cultures of Human Keratinocytes

Stefan Duensing,1 Anette Duensing,2 Elsa R. Flores,3,dagger Anh Do,3 Paul F. Lambert,3 and Karl Münger1,*

Department of Pathology and Harvard Center for Cancer Biology1 and Department of Pathology, Solid Tumor Cytogenetics, Brigham and Women's Hospital,2 Harvard Medical School, Boston, Massachusetts 02115, and McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 537063

Received 12 March 2001/Accepted 10 May 2001

Primary human keratinocytes with ectopic expression of high-risk human papillomavirus (HPV) E6 and E7 oncoproteins display abnormal centrosome numbers, multipolar mitoses, and aneusomy. However, it has not been explored whether these abnormalities can occur in cells containing HPV episomes where E6 and E7 expression is under viral transcriptional control. Here, we demonstrate that centrosome abnormalities and genomic instability occur in organotypic raft cultures of human keratinocytes with episomal HPV-16 even at low copy numbers. We conclude that HPV-16 DNA, when maintained as an episome, can disturb centrosome homeostasis and subvert genomic integrity of the host cell during early stages of the viral infection.

* Corresponding author. Mailing address: Department of Pathology and Harvard Center for Cancer Biology, Harvard Medical School, Armenise Research Building, 200 Longwood Ave., Boston, MA 02115-5701. Phone: (617) 432-2878. Fax: (617) 432-0426. E-mail: karl_munger{at}hms.harvard.edu.

dagger Present address: Department of Biology, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.

Journal of Virology, August 2001, p. 7712-7716, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7712-7716.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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