Characterization Of The Papillomavirus Regulatory Proteins

McBride, Alison

Abstract

Papillomaviruses have a remarkable infectious cycle that depends on the development of a stratified epithelium. In this life cycle, there are three different modes of viral DNA replication. The virus initially infects the lower, dividing layers of the epithelium;viral DNA is transported to the nucleus where it must escape intrinsic host defenses and establish the genome as a stable, extra-chromosomal, autonomously replicating element. Next, in the maintenance phase, genomes replicate at low copy number in concert with host DNA and are partitioned to daughter cells upon cell division. Finally, as infected cells differentiate and traffic to the surface of the epithelium, high level viral DNA amplification is triggered to generate new progeny virus. We have studied all three phases of viral replication in this review cycle. Our objective is to define the precise molecular mechanisms involved in viral and cellular replication. This insight will enhance our ability to design therapeutics for viral infection and associated cancers.

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 #: 1ZIAAI000713-21
• Application #: 8946308
• Support Year: 21
• Fiscal Year: 2014

Institution

• Name: Niaid Extramural Activities

Publications

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 :

McBride, Alison A; Münger, Karl (2018) Expert Views on HPV Infection. Viruses 10:

McBride, Alison A (2017) Oncogenic human papillomaviruses. Philos Trans R Soc Lond B Biol Sci 372:

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:

Van Doorslaer, Koenraad; McBride, Alison A (2016) Molecular archeological evidence in support of the repeated loss of a papillomavirus gene. Sci Rep 6:33028