A Novel In Vivo Infection Model To Study Papillomavirus-Mediated Disease of the Female Reproductive Tract

Abstract

Tractable and efficient models of papillomavirus-induced pathogenesis are limited due to the strict species-specific and tissue-specific tropism of these viruses. Here, we report a novel preclinical murine model of papillomavirus-induced cervicovaginal disease in wild-type, immunocompetent mice using the recently discovered murine papillomavirus, MmuPV1. In this model, MmuPV1 establishes persistent viral infections in the mucosal epithelia of the female reproductive tract, a necessary component needed to accurately mimic HPV-mediated neoplastic disease in humans. Persistent MmuPV1 infections were able to induce progressive neoplastic disease and carcinogenesis, either alone or in combination with previously identified cofactors of papillomavirus-induced disease. This new model will provide a much-needed platform for basic and translational studies on both papillomavirus infection and associated disease in immunocompetent mice.