Adeno-associated virus Rep78 inhibits oncogenic transformation of primary human keratinocytes by a human papillomavirus type 16-ras chimeric

Abstract

Seroepidemiologic studies demonstrate that adeno-associated virus (AAV) infection is negatively associated with cervical cancer. This inverse association may be due to an ability of AAV to inhibit the role of human papillomavirus (HPV) in cervical carcinogenesis. In support of this hypothesis AAV has been demonstrated to inhibit several papillomavirus types, including bovine papillomavirus type 1 and human papillomaviruses types 16 and 18 (HPV-16/18) in tissue culture. The AAV-encoded Rep78 protein was responsible for this inhibition. These previous studies, however, were largely carried out in immortalized mouse fibroblasts. This cell type is likely not to be the most accurate model cell type for studying HPV-associated cervical carcinogenesis. In this study it is demonstrated that AAV Rep78 protein inhibits oncogenic transformation of freshly explanted primary human foreskin keratinocytes by an HPV-16/ras chimeric genome. Such cells are the natural host cell type for HPV-16/18 infection. It is also demonstrated that the HPV-16 P97 promoter is specifically inhibited by Rep78 in a transient CAT assay. These data further extend our knowledge of the AAV-papillomavirus interaction and provide a model for investigating the negative association of AAV with cervical cancer.