Abstract

Papillomavirus infection causes persistent epithelial lesions, known as papillomas. Papillomavirus infection is also associated with the development of cervical cancer. Our laboratory has established that papillomavirus genomes and the E2 transactivator protein interact with cellular mitotic chromosomes in dividing cells. This ensures that viral genomes are properly segregated to daughter cells and are retained within the nucleus.
Our aim i s to elucidate the mechanisms by which the E2 proteins control the viral life cycle. Using mass spectrometry we have characterized cellular proteins that form complexes with the E2 proteins from multiple papillomaviruses. We have demonstrated that the viral E2 protein binds to active promoters in the human genome with the cellular Brd4 protein.We propose that the viral DNA is also tethered to these sites and that this prevents silencing. We have identified persistent and distinctive chromatin binding sites for the E2-Brd4 complex on human chromosomes. These novel sites persist in both interphase and mitotic cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI000713-16
Application #
7964358
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2009
Total Cost
$391,257
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

McBride, Alison A; Münger, Karl (2018) Expert Views on HPV Infection. Viruses 10:
Bentley, Peris; Tan, Min Jie Alvin; McBride, Alison A et al. (2018) The SMC5/6 complex interacts with the papillomavirus E2 protein and influences maintenance of viral episomal DNA. J Virol :
Stepp, Wesley H; Stamos, James D; Khurana, Simran et al. (2017) Sp100 colocalizes with HPV replication foci and restricts the productive stage of the infectious cycle. PLoS Pathog 13:e1006660
Moquin, Stephanie A; Thomas, Sean; Whalen, Sean et al. (2017) The Epstein-Barr virus episome maneuvers between nuclear chromatin compartments during reactivation. J Virol :
McBride, Alison A (2017) The Promise of Proteomics in the Study of Oncogenic Viruses. Mol Cell Proteomics 16:S65-S74
Porter, Samuel S; Stepp, Wesley H; Stamos, James D et al. (2017) Host cell restriction factors that limit transcription and replication of human papillomavirus. Virus Res 231:10-20
McBride, Alison A (2017) Mechanisms and strategies of papillomavirus replication. Biol Chem 398:919-927
Van Doorslaer, Koenraad; Chen, Dan; Chapman, Sandra et al. (2017) Persistence of an Oncogenic Papillomavirus Genome Requires cis Elements from the Viral Transcriptional Enhancer. MBio 8:
McBride, Alison A (2017) Oncogenic human papillomaviruses. Philos Trans R Soc Lond B Biol Sci 372:
Van Doorslaer, Koenraad; McBride, Alison A (2016) Molecular archeological evidence in support of the repeated loss of a papillomavirus gene. Sci Rep 6:33028

Showing the most recent 10 out of 25 publications