Papillomaviruses are small DNA tumor viruses, a subset of which are associated with human cancers. HPV-16 represents the prototype oncogenic mucosotropic HPV owing to its frequent association with oral, cervical, penile and anal cancers. In the Lambert laboratory, we study the oncogenic potential of HPV-16 and its life cycle. Over the current funding period we have elucidated the roles of E6 and E7 in cancer using transgenic mouse models, and have established in our hands the tools for studying the role of individual viral genes in the viral life cycle. These latter studies led to the demonstration of E7's requirement in the productive stage of the viral life cycle in which the virus reprograms terminally differentiated epithelial cells to support viral DNA amplification. We have likewise initiated studies on three other viral genes, E6, E5, and E1; each of which possess biological properties that are suggestive of their roles in the propagation of virus in its natural host. In the process of studying E1, we discovered the ability of papillomavirus genomes to replicate in mammalian cells as well as in yeast independently of E1.
The aims of this Project are focused on further understanding the role of E7, E6, and E5 in the viral life cycle, and to distinguish the roles of E1-dependent versus E1-independent replication in the viral life cycle. These studies will continue to make use of the HPV-16 virus as a prototype mucosotropic virus for study in the laboratory.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA022443-26
Application #
6752166
Study Section
Project Start
2003-05-29
Project End
2008-04-30
Budget Start
2003-05-29
Budget End
2004-04-30
Support Year
26
Fiscal Year
2003
Total Cost
$259,451
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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Uberoi, Aayushi; Yoshida, Satoshi; Lambert, Paul F (2018) Development of an in vivo infection model to study Mouse papillomavirus-1 (MmuPV1). J Virol Methods 253:11-17
Djavadian, Reza; Hayes, Mitchell; Johannsen, Eric (2018) CAGE-seq analysis of Epstein-Barr virus lytic gene transcription: 3 kinetic classes from 2 mechanisms. PLoS Pathog 14:e1007114
Chakravorty, Adityarup; Sugden, Bill (2018) Long-distance communication: Looping of human papillomavirus genomes regulates expression of viral oncogenes. PLoS Biol 16:e3000062
Chiu, Ya-Fang; Sugden, Bill (2018) Plasmid Partitioning by Human Tumor Viruses. J Virol 92:
Shin, Myeong-Kyun; Payne, Susan N; Bilger, Andrea et al. (2018) Activating Mutations in Pik3caContribute to Anal Carcinogenesis in the Presence or Absence of HPV-16 Oncogenes. Clin Cancer Res :

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