A novel pre-clinical murine model to study the life cycle and progression of cervical and anal papillomavirus infections

Background: Papillomavirus disease and associated cancers remain a significant health burden in much of the world. The current protective vaccines, Gardasil and Cervarix, are expensive and not readily available to the underprivileged. In addition, the vaccines have not gained wide acceptance in the United States nor do they provide therapeutic value. Papillomaviruses are strictly species specific and thus human viruses cannot be studied in an animal host. An appropriate model for mucosal disease has long been sought. We chose to investigate whether the newly discovered mouse papillomavirus, MmuPV1, could infect mucosal tissues in Foxn1^nu/Foxn1^nu mice. Methods: The vaginal and anal canals of Foxn1^nu/Foxn1^nu mice were gently abraded using Nonoxy-nol-9 and "Doctor's BrushPicks " and MmuPV1 was delivered into the vaginal tract or the anal canal. Results: Productive vaginal, cervical and anal infections developed in all mice. Vaginal/cervical infections could be monitored by vaginal lavage. Dysplasias were evident in all animals. Conclusions: Anogenital tissues of a common laboratory mouse can be infected with a papillomavirus unique to that animal. This observation will pave the way for fundamental virological and immunological studies that have been challenging to carry out heretofore due to lack of a suitable model system.