Wild-type (WT) and E7 K81S mutant viral genomes replicated as extrachromosomal circular DNAs to comparable levels in mouse keratinocytes. Based on the published structure of the HPV18 E7/PTPN14 complex, we generated a MmuPV1 E7 mutant, E7 K81S, that was defective for binding PTPN14. Here, we confirmed the MmuPV1 E7-PTPN14 interaction. We previously identified Protein Tyrosine Phosphatase Non-Receptor Type 14 (PTPN14), a tumor suppressor targeted by HPV E7 proteins, as a putative cellular target of MmuPV1 E7. Murine papillomavirus (MmuPV1) provides a powerful tool to study the roles of papillomavirus genes in pathogenesis arising from a natural infection. Species-specific barriers limit the ability to study HPV pathogenesis in animal models. Human papillomaviruses (HPVs) contribute to approximately 5% of all human cancers.