Human papillomavirus DNA replication mediated by simian virus 40 T antigen in trans

The putative E1 gene product of papillomaviruses is thought to be involved in the initiation of viral replication, as large-T antigen (T antigen) is in the case of polyomaviruses. Mouse cell lines cloned after transformation by a plasmid consisting of the simian virus 40 (SV40) early region and the complete genome of human papillomavirus type 16 (HPV16) maintained episomal plasmid DNA. In contrast, the DNAs of either SV40 or HPV16, when employed separately in transfection experiments, were consistently integrated into the host DNA. To test the hypothesis that SV40 T antigen might be involved in the replication of the hybrid plasmids, HPV16 DNA was used in a transient replication assay for transfection of either CV-1 or COS-7 cells. The HPV16 DNA replicated to a high copy number in the T antigen-producing COS-7 cells, but failed to replicate in the CV-1 cells. To define the HPV16 sequences that were essential for the plasmid maintenance in SV40 T antigen-producing cells, restriction fragments of HPV16 were analysed for their replication capacity in COS-7 cells. Here it is reported that the presence of the coding region of the putative E1 gene product of HPV16 together with the 5' transcriptional control elements is essential and is sufficient to support plasmid replication mediated by SV40 T antigen in trans.