ADENOASSOCIATED VIRUS REP78 INHIBITS ONCOGENIC TRANSFORMATION OF PRIMARY HUMAN KERATINOCYTES BY A HUMAN-PAPILLOMAVIRUS TYPE 16-RAS CHIMERIC

Seroepidemiologic studies demonstrate that adeno-associated virus (AAV ) infection is negatively associated with cervical cancer. This invers e association may be due to an ability of AAV to inhibit the role of h uman papillomavirus (HPV) in cervical carcinogenesis. In support of th is hypothesis AAV has been demonstrated to inhibit several papillomavi rus types, including bovine papillomavirus type 1 and human papillomav iruses types 16 and 18 (HPV-16/18) in tissue culture. The AAV-encoded Rep78 protein was responsible for this inhibition, These previous stud ies, however, were largely carried out in immortalized mouse fibroblas ts. This cell type is likely not to be the most accurate model cell ty pe for studying HPV-associated cervical carcinogenesis, In this study it is demonstrated that AAV Rep78 protein inhibits oncogenic transform ation 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 p romoter is specifically inhibited by Rep78 in a transient CAT assay. T hese data further extend our knowledge of the AAV-papillomavirus inter action and provide a model for investigating the negative association of AAV with cervical cancer. (C) 1997 Academic Press.