Fig. 2.

Overview of common types of animal models used to study the role of small DNA tumor viruses in human cancers. A. Infection models used to study the papillomavirus life cycle and pathogenesis. Pseudoviruses contain plasmid DNA, often expressing reporter proteins like GFP (green circles), encapsidated by the HPV capsid proteins in vitro. Natural viruses, such as those that infect laboratory hosts, are often used to establish animal models of papillomavirus infection and disease. B. Constitutive transgenic models express transgenes (Viral Protein; red) driven by either ubiquitous (e.g., ROSA26) or cell/tissue-specific (e.g., keratin 14; K14) promoters (shown as arrows). C. Conditional transgenic models often employ recombinase systems, such as the Cre/loxP system, to direct either constitutive or inducible transgene expression. Using Cre/loxP as an example, conditional transgene cassettes include a promoter (blue arrow) and a transgene (Viral Protein; red) separated by a transcriptional stop sequence flanked by two loxP sequences (loxP-stop-loxP; LSL; green). Presence of the LSL will prevent viral protein expression in animals expressing this cassette. To achieve tissue-specific constitutive expression (top right), mice carrying the conditional allele can be crossed with mice that express Cre recombinase driven by a tissue-specific promoter. The example shown here is K14Cre, which will direct expression of the viral protein (red dots) in K14-positive cells (shown in green) in basal cells of the stratified epithelium. To achieve tissue-specific inducible expression (bottom right), mice carrying the conditional allele can be crossed with mice that express a Cre recombinase fusion protein (e.g., Cre-ERT) driven by a cell-specific promoter. The Cre-ERT fusion protein is inactive until bound by its ligand (tamoxifen; Tam). In the absence of Tam, there is no viral protein expression in K14-positive cells. Upon administration of Tam, the viral protein (red) is now expressed only in K14-positive cells (green). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)