title: Progression from productive infection to integration and oncogenic transformation in human papillomavirus type 59-immortalized foreskin keratinocytes.
abstract: Studies of changes in the virus and host cell upon progression from human papillomavirus (HPV) episomal infection to integration are critical to understanding HPV-related malignant transformation. However, there exist only a few in vitro models of both productive HPV infection and neoplastic progression on the same host background. We recently described a unique foreskin keratinocyte cell line (ERIN 59) that contains HPV 59 (a close relative of HPV 18). Early passages of ERIN 59 cells (passages 9-13) contained approximately 50 copies of episomes/cell, were feeder cell-dependent, and could be induced to differentiate and produce infectious virus in a simple culture system. We now report that late passage cells (passages greater than 50) were morphologically different from early passage cells, were feeder cell independent, and did not differentiate or produce virus. These late passage cells contained HPV in an integrated form. An integration-derived oncogene transcript was expressed in late passage cells. The E2 open reading frame was interrupted in this transcript at nucleotide 3351. Despite a lower viral genome copy number in late passage ERIN 59 cells, expression of E6/E7 oncogene transcripts was similar to early passage cells. We conclude that ERIN 59 cells are a valuable cell line representing a model of progression from HPV 59 episomal infection and virus production to HPV 59 integration and associated oncogenic transformation on the same host background.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Helena
authors.initials: H
authors.lastname: Spartz
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lehr
authors.forename: Benyue
authors.initials: B
authors.lastname: Zhang
authors.forename: Ann
authors.initials: A
authors.lastname: Roman
authors.forename: Darron R
authors.initials: DR
authors.lastname: Brown
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002472:Cell Transformation, Viral; D006801:Humans; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000473:pathology* / Q000821:virology*; D051379:Mice; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D027383:Papillomaviridae; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D016662:Virus Integration
chemical_list: D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral