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Development and characterization of a novel xenograft model permissive for human papillomavirus DNA amplification and late gene expression

¹ Glaxo-Wellcome Research Laboratories, Beckenham, Kent BR3 3BS
and² Department of Experimental Dermatology, The London Hospital Medical School, Whitechapel, London E1 2AD, UK

Human papillomaviruses (HPVs) are important human pathogens associated with a range of epithelial neoplasia. The rising incidence of HPV infection and association of HPV with malignancy has led to increased interest in appropriate management of these infections. Development of new therapies for viral warts has been frustrated by the lack of availability of models permissive for viral replication. Here we describe the development of a HPV-severe combined immunodeficient mouse model which reproduces mature HPV-infected epithelia. Grafting of anogenital and laryngeal papillomas harbouring either HPV-6 or HPV-11 resulted in the formation of a differentiated neo-epithelium exhibiting the hallmark features of HPV infection including basal hyperplasia, acanthosis and koilocytosis. The reformed warty epithelium contained amplified HPV DNA and expressed capsid protein in the differentiated layers. A striking feature is the production of macroscopic papillomata in an anatomically relevant and accessible site, providing a system of particular relevance for the temporal evaluation of developing lesions and selection of antiviral agents.

^* Author for correspondence. Fax +44 181 663 3532.

Received 24 April 1995; accepted 31 July 1995.

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