The E5 gene of HPV-16 enhances keratinocyte immortalization by full-length DNA.

Human papillomavirus type 16 (HPV-16) is the most common papillomavirus genome found in human cervical cancers and its DNA is capable of immortalizing primary keratinocytes in vitro. When expressed by their native promoter, two separate HPV-16 oncogenes, E6 and E7, cooperate to immortalize primary human keratinocytes. Early HPV cervical lesions express abundant amounts of E5-specific RNA, and using a quantitative keratinocyte immortalization assay, we demonstrate here that E5 can act in cis to increase (4-10 fold) the efficiency of cellular immortalization by E6/E7. These results suggest that the expression of the HPV-16 E5 gene may play a role in the pathogenesis of early HPV infections by potentiating the effects of E6/E7.