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Published online ahead of print on 19 August 2009 as doi:10.1099/vir.0.012872-0
Journal of General Virology 2009;90:2855.

A more recent version of this article appeared on December 1, 2009 J Gen Virol (2009), DOI 10.1099/vir.0.012872-0
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Spontaneous tumor development in human papillomavirus type 8 E6 transgenic mice and rapid induction by UV-light exposure and wounding.

Gian Paolo Marcuzzi1,4, Martin Hufbauer1, Hans Udo Kasper2, Sönke Jan Weißenborn1, Sigrun Smola3 and Herbert Pfister1

1 Institute of Virology, Cologne;
2 Institute of Pathology, Cologne;
3 Institute of Virology, Homburg

4 E-mail: gian.marcuzzi{at}uk-koeln.de

The cutaneous human papillomavirus 8 (HPV8) is carcinogenic in patients with epidermodysplasia verruciformis. Transgenic mice with the complete early region (CER) of HPV8 spontaneously developed papillomas, dysplasia and squamous cell carcinomas of the skin. To characterize the role of individual early genes in carcinogenesis E6 and E6/E7 were expressed separately in transgenic mice. Nearly all HPV8-E6 positive mice spontaneously developed multifocal tumors, characterized by papillomatosis, hyperkeratosis and varying degrees of epidermal dysplasia. In 6% of the cases the tumors became malignant, comparable with HPV8-CER mice. Thus, in the murine epidermis, E6 is the major oncogene, necessary and sufficient to induce spontaneous tumor development up to squamous cell carcinoma. To evaluate synergistic effects of UV-light or wound healing, the skin of HPV8 mice was irradiated with UVA- and UVB- light or wounded with punch biopsies. These treatments induced papillomatosis in HPV8-CER and -E6 mice within three weeks. Irradiation with UVA alone did not induce papillomatosis and UVB alone had a weaker effect than UVA/B, pointing to a synergistic role of UVA in UVB induced papillomatosis. An HPV8 infection persisting over decades in interaction with sun burns and wound healing processes may be a relevant cause of skin cancer in man.

Received 22 April 2009; accepted 17 August 2009.




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