HPV gene expression relies tightly on its enhancer which in turn restri its activity to keratinocytes. In these permissive cells, viral expression is modulated by their differentiation status. The mechanisms that direct this selective transcriptional control have not been elucidated. We propose thus to characterise the structure, function, and regulation of the HPV 18 enhancer, and to identify the cellular transcription factors participating to its cell-type specificity. As AP-1 plays a central role in the enhancer activity, we will first look at the relative distribution of its different Jun/Fos members in a normal differentiating epithelium and compare it to a virally infected tissue. We will also examine the binding of these Jun/Fos heterodimers to the HPV 18 AP-1 site. We will next identify the unknown transcription factors that synergistically interact with the Jun/Fos complex, and study their expression in the epithelium and other tissues.