Development and characterization of a novel xenograft model permissive for human papillomavirus DNA amplification and late gene expression.
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 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.
Sexton
C J
CJ
Glaxo-Wellcome Research Laboratories, Beckenham, Kent, UK.
Williams
A T
AT
Topley
P
P
Shaw
R J
RJ
Lovegrove
C
C
Leigh
I
I
Stables
J N
JN
D000818:Animals; D002213:Capsid / Q000032:analysis; D003218:Condylomata Acuminata / Q000821:virology; D004261:DNA Replication; D004195:Disease Models, Animal; D004848:Epithelium / Q000737:chemistry / Q000821:virology; D015870:Gene Expression; D006801:Humans; D007633:Keratins / Q000032:analysis; D007822:Laryngeal Neoplasms / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010212:Papilloma / Q000821:virology; D027383:Papillomaviridae / Q000502:physiology*; D030361:Papillomavirus Infections / Q000821:virology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011498:Protein Precursors / Q000032:analysis; D012867:Skin / Q000737:chemistry; D016038:Skin Transplantation; D014183:Transplantation, Heterologous; D014412:Tumor Virus Infections / Q000821:virology*; D014779:Virus Replication
D018809:Proliferating Cell Nuclear Antigen; D011498:Protein Precursors; C032253:involucrin; D007633:Keratins