Pl. Hermonat et al., ADENOASSOCIATED VIRUS REP78 INHIBITS ONCOGENIC TRANSFORMATION OF PRIMARY HUMAN KERATINOCYTES BY A HUMAN-PAPILLOMAVIRUS TYPE 16-RAS CHIMERIC, Gynecologic oncology, 66(3), 1997, pp. 487-494
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.