title: The E1 protein of human papillomavirus type 16 is dispensable for maintenance replication of the viral genome.
abstract: Papillomavirus genomes are thought to be amplified to about 100 copies per cell soon after infection, maintained constant at this level in basal cells, and amplified for viral production upon keratinocyte differentiation. To determine the requirement for E1 in viral DNA replication at different stages, an E1-defective mutant of the human papillomavirus 16 (HPV16) genome featuring a translation termination mutation in the E1 gene was used. The ability of the mutant HPV16 genome to replicate as nuclear episomes was monitored with or without exogenous expression of E1. Unlike the wild-type genome, the E1-defective HPV16 genome became established in human keratinocytes only as episomes in the presence of exogenous E1 expression. Once established, it could replicate with the same efficiency as the wild-type genome, even after the exogenous E1 was removed. However, upon calcium-induced keratinocyte differentiation, once again amplification was dependent on exogenous E1. These results demonstrate that the E1 protein is dispensable for maintenance replication but not for initial and productive replication of HPV16.
authors.affiliation: Division of Virology, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan.
authors.forename: Nagayasu
authors.initials: N
authors.lastname: Egawa
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nakahara
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Ohno
authors.forename: Mako
authors.initials: M
authors.lastname: Narisawa-Saito
authors.forename: Takashi
authors.initials: T
authors.lastname: Yugawa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Fujita
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamato
authors.forename: Yukikazu
authors.initials: Y
authors.lastname: Natori
authors.forename: Tohru
authors.initials: T
authors.lastname: Kiyono
mesh_terms: D002460:Cell Line; D004261:DNA Replication; D016679:Genome, Viral; D052162:Human papillomavirus 16 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000821:virology*; D014779:Virus Replication
chemical_list: C093478:E1 protein, Human papillomavirus 16; D009856:Oncogene Proteins, Viral