期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 7, 页码 2094-2099出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0308615100
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资金
- NCI NIH HHS [CA-85747, R01 CA085747] Funding Source: Medline
- NHLBI NIH HHS [P50 HL061234, HL61234, P01 HL051670, HL51670] Funding Source: Medline
- NIAID NIH HHS [T32 AI007533, T32AI07533, AI-052049, P01 AI052049] Funding Source: Medline
- NIA NIH HHS [R01AG18265, R01 AG018265] Funding Source: Medline
- NIDCD NIH HHS [T32DC000040, K08 DC005627-01, T32 DC000040, K08 DC005627] Funding Source: Medline
- NIDDK NIH HHS [P30 DK054759, DK54759] Funding Source: Medline
Human papillomavirus type 16 (HPV16) infection is a major risk factor for the development of squamous cell cancers of the cervix and of the head and neck. A major barrier to understanding the progression from initial infection to cancer has been the lack of in vitro models that allow infection, replication, and persistence of the viral genome as an episome in differentiated epithelial cells. To overcome this barrier, we designed an adenoviral delivery vector that contained a full HPV16 genome flanked by LoxP homologous recombination sites and a fluorescent reporter that was expressed only after the HPV genome was excised by Cre recombinase. This system delivered circular HPV16 genomes to cervical epithelial cells and well differentiated human airway epithelia. After delivery, the HPV16 genome replicated and persisted as an episome in cervical keratinocytes. These cells developed an immortalized phenotype and a dysplastic epithelial appearance. Moreover, induction of differentiation led to the expression of late genes and production of infectious HPV16 virions. This work provides a means of introducing biologically active HPV genomes into epithelial cells, which are normally difficult to transfect. These methods allow the study of HPV genome replication and gene expression in the earliest stages of HPV genome establishment, and they may provide a means to study nononcogenic HPV viral types.
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