HPV Elements Required for Alpha HPV Genome Replication and Partitioning

McBride, Alison

Abstract

Each papillomavirus is species specific and replicates persistently in a specific type of cutaneous or mucosal epithelium. The keratinocytes of the basal layer of the epithelium harbor a reservoir of replicating viral genomes and therefore are the ideal cells in which to study the mechanisms by which HPV establishes persistent infection. Papillomaviruses will only undergo their complete life cycle and generate progeny virus in the tissue culture equivalent of a stratified epithelium. This process requires establishing stably replicating viral DNA genomes in primary human keratinocytes and culturing them in three-dimensional skin equivalents.
The aims of this project are to determine the mechanism of extrachromosomal replication and partitioning of the viral genome.

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 #: 1ZIAAI001073-10
• Application #: 9566693
• Support Year: 10
• Fiscal Year: 2017

Institution

• Name: Niaid Extramural Activities

Publications

McBride, Alison A (2017) Playing with fire: consequences of human papillomavirus DNA replication adjacent to genetically unstable regions of host chromatin. Curr Opin Virol 26:63-68

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; Porter, Samuel; McKinney, Caleb et al. (2016) Novel recombinant papillomavirus genomes expressing selectable genes. Sci Rep 6:37782

McKinney, Caleb C; Kim, Min Jung; Chen, Dan et al. (2016) Brd4 Activates Early Viral Transcription upon Human Papillomavirus 18 Infection of Primary Keratinocytes. MBio 7:

Dooley, Katharine E; Warburton, Alix; McBride, Alison A (2016) Tandemly Integrated HPV16 Can Form a Brd4-Dependent Super-Enhancer-Like Element That Drives Transcription of Viral Oncogenes. MBio 7:

Sakakibara, Nozomi; Chen, Dan; McBride, Alison A (2013) Papillomaviruses use recombination-dependent replication to vegetatively amplify their genomes in differentiated cells. PLoS Pathog 9:e1003321

McBride, Alison A; Sakakibara, Nozomi; Stepp, Wesley H et al. (2012) Hitchhiking on host chromatin: how papillomaviruses persist. Biochim Biophys Acta 1819:820-5

Sakakibara, Nozomi; Mitra, Ruchira; McBride, Alison A (2011) The papillomavirus E1 helicase activates a cellular DNA damage response in viral replication foci. J Virol 85:8981-95