The human papillomavirus type 11 E1^E4 protein is not essential for viral genome amplification

An abundant human papillomavirus (HPV) protein E1^E4 is expressed late in the virus life cycle in the terminally differentiated layers of epithelia. The expression of E1^E4 usually coincides with the onset of viral DNA amplification. However, the function of E1^E4 in viral life cycle is not completely understood. To examine the role of E1^E4 in the virus life cycle, we introduced a single nucleotide change in the HPV-11 genome to result in a truncation of E1^E4 protein without affecting the E2 amino acid sequence. This mutated HPV-11 genome was introduced into a human foreskin keratinocyte cell line immortalized by the catalytic subunit of human telomerase, deficient in p16INK4a expression, and previously shown to support the HPV-11 life cycle when grown in organotypic raft culture. We have demonstrated that E1^E4 is dispensable for HPV-11 viral DNA amplification in the late stages of the viral life cycle.