Epithelial differentiation fails to support replication of cloned human papillomavirus type 16 DNA in transfected keratinocytes

Research on the life cycle of human papillomaviruses (HPVs) has suffered from the lack of a model system that allows the use of molecularly cloned HPV DNA. In this study, we analyzed replication of molecularly cloned HPV-16 genomes after transfection into cells of two human keratinocyte cell lines. Transfected cells were grown in cell culture (in vitro) or in transplantation chambers on the flanks of nude mice (in vivo). When DNA was extracted after different time intervals, replication of HPV-16 DNA could not be detected. Even the formation of a stratified epithelium under in vivo conditions failed to support vegetative replication. In contrast, transfection of molecularly cloned HPV-11 DNA resulted in replication of viral DNA in vitro. It seems likely that besides epithelial cell differentiation, a number of other factors influence HPV-16 replication.