Adeno-associated virus inhibits human papillomavirus type 16: a viral interaction implicated in cervical cancer

Human papillomavirus (HPV) infection, in particular that by HPV type 16, is positively associated with cervical/genital cancer. In contrast, human adeno-associated virus (AAV) infection is negatively associated with these same cancers. AAV has also been found to inhibit the oncogenic properties of a variety of DNA viruses, including bovine papillomavirus type 1, a relative of HPV-16. Taken together, these findings suggested the possibility that AAV and HPV-16 might interact, with AAV inhibiting HPV-16's oncogenic phenotype. Here this hypothesis is addressed using tissue culture assays measuring HPV-16-directed phenotypes. It is found that the cotransfection of AAV type 2 Rep78-positive plasmids resulted in the inhibition of HPV-16 sequence containing plasmids in oncogenic transformation/focus formation, G418-resistant colony formation, and chloramphenicol acetyltransferase expression assays. These data are consistent with the hypothesis that AAV's negative association with cervical cancer is at least partially due to its ability to inhibit HPV-16 expression.