PMID: 8610168Apr 2, 1996Paper

In vitro synthesis of oncogenic human papillomaviruses requires episomal genomes for differentiation-dependent late expression

Proceedings of the National Academy of Sciences of the United States of America
M G FrattiniL A Laimins

Abstract

Human papillomavirus (HPV) types 16, 18, 31, and 51 are the etiologic agents of many anogenital cancers including those of the cervix. These "high risk" HPVs specifically target genital squamous epithelia, and their lytic life cycle is closely linked to epithelial differentiation. We have developed a genetic assay for HPV functions during pathogenesis using recircularized cloned HPV 31 genomes that were transfected together with a drug resistance marker into monolayer cultures of normal human foreskin keratinocytes, the natural host cell. After drug selection, cell lines were isolated that stably maintained HPV 31 DNA as episomes and underwent terminal differentiation when grown in organotypic raft cultures. In differentiated rafts, the expression of late viral genes, amplification of viral DNA, and production of viral particles were detected in suprabasal cells. This demonstrated the ability to synthesize HPV 31 virions from transfected DNA templates and allowed an examination of HPV functions during the vegetative viral life cycle. We then used this system to investigate whether an episomal genome was required for the induction of late viral gene expression. When an HPV 31 genome (31E1*) containing a missense mutation in the ...Continue Reading

References

Jul 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·C M ChiangL T Chow
Dec 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·R KirnbauerJ T Schiller
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·M G Frattini, L A Laimins

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Citations

Dec 7, 2000·Genes, Chromosomes & Cancer·A CottageM Stanley
Mar 9, 2005·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·John Doorbar
Mar 1, 1997·Clinics in Dermatology·M FavreG Orth
Mar 1, 1997·Clinics in Dermatology·D R Lowy
Mar 12, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·R W ChenA Vaheri
Feb 24, 2005·Clinical Obstetrics and Gynecology·Luis Alfonso Padilla-Paz
Nov 12, 2005·Current Opinion in Otolaryngology & Head and Neck Surgery·John H Lee, Richard J Smith
Jan 28, 2009·Genes & Development·Denise A Galloway
May 3, 2013·Journal of Virology·Stephen SchuckArne Stenlund
Apr 23, 2002·Journal of Virology·Craig MeyersKathrin U Jansen
Aug 7, 2002·Journal of Virology·Yijan E ChangLaimonis A Laimins
Nov 5, 2002·Journal of Virology·Kong-Nan Zhao, Ian H Frazer
Feb 14, 2004·Journal of Virology·Stephen T OhLaimonis A Laimins

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