DNA from bovine papillomavirus type 2 induces warts in a xenograft model

Bovine papillomavirus (BPV) type 2 DNA was inoculated into calf scrotal skin before grafting onto severe combined immunodeficient mice. Inoculation with viral DNA isolated from a bovine wart induced fibropapillomas that exhibited all the morphological features of a BPV infection in cattle. The production of capsid protein and infectious BPV2 particles was demonstrated by immunohistochemistry and a transformed cell focus assay. In contrast, the injection of molecularly cloned viral genomic DNA led to the induction of papilloma-like lesions in the epidermis, but a fibroma was not formed. In addition, only early genes were expressed and infectious virus particles could not be detected. A restriction enzyme accessibility assay suggested that the methylation status of the molecularly cloned BPV2 DNA was different from that of native viral DNA. A possible correlation between methylation status and tumour phenotype is discussed.