Characterization of three rabbit oral papillomavirus oncogenes.

Rabbit oral papillomavirus (ROPV) induces warts in mucosal tissues, and represents a useful model for understanding host-virus interactions that are reflected in mucosal/HPV infections. ROPV induces benign papillomas that regress in 100% of infected rabbits. We previously reported the complete genome sequence of ROPV. However, the oncogenic potential of this virus is unknown because of immunologically mediated regression. The purpose of this study was to characterize the transforming proteins of E6, E7, and E8 genes of ROPV. E6, E7, and E8 genes of ROPV were cloned into the expression vector PCR3. Two hybrid CRPV-ROPV E6 genes were also constructed and tested together with the three wild-type ROPV genes. Each construct was transfected into NIH3T3 cells and stable transfected cell lines were established. Transforming properties of ROPV E6, E7, and E8 were tested via anchorage-independent growth of cells in agar plates and tumor growth in athymic mice. Cells with ROPV E6, E7, or E8 formed colonies in agar and tumors in athymic mice. These observations suggest that ROPV E6, E7, and E8 are oncogenic.