Next Article in Journal
Live Attenuated Influenza Vaccine contains Substantial and Unexpected Amounts of Defective Viral Genomic RNA
Previous Article in Journal
Natural History of HPV Infection across the Lifespan: Role of Viral Latency
Previous Article in Special Issue
LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends
Article Menu

Export Article

Open AccessReview
Viruses 2017, 9(10), 268; doi:10.3390/v9100268

Why Human Papillomaviruses Activate the DNA Damage Response (DDR) and How Cellular and Viral Replication Persists in the Presence of DDR Signaling

1
VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USA
2
Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA
*
Author to whom correspondence should be addressed.
Received: 29 August 2017 / Revised: 12 September 2017 / Accepted: 15 September 2017 / Published: 21 September 2017
(This article belongs to the Special Issue Viruses and the DNA Damage Response)
View Full-Text   |   Download PDF [1157 KB, uploaded 21 September 2017]   |  

Abstract

Human papillomaviruses (HPV) require the activation of the DNA damage response (DDR) in order to undergo a successful life cycle. This activation presents a challenge for the virus and the infected cell: how does viral and host replication proceed in the presence of a DDR that ordinarily arrests replication; and how do HPV16 infected cells retain the ability to proliferate in the presence of a DDR that ordinarily arrests the cell cycle? This raises a further question: why do HPV activate the DDR? The answers to these questions are only partially understood; a full understanding could identify novel therapeutic strategies to target HPV cancers. Here, we propose that the rapid replication of an 8 kb double stranded circular genome during infection creates aberrant DNA structures that attract and activate DDR proteins. Therefore, HPV replication in the presence of an active DDR is a necessity for a successful viral life cycle in order to resolve these DNA structures on viral genomes; without an active DDR, successful replication of the viral genome would not proceed. We discuss the essential role of TopBP1 in this process and also how viral and cellular replication proceeds in HPV infected cells in the presence of DDR signals. View Full-Text
Keywords: HPV; human papillomavirus; replication; initiation; life cycle; DNA damage response; TopBP1; E1; E2; ATM (ataxia-telangiectasia mutated); ATR (ataxia telangiectasia and Rad3 related); DNA damage signaling; cervical cancer; head and neck cancer; homologous recombination; MRN (Mre11-Rad50-Nbs1) HPV; human papillomavirus; replication; initiation; life cycle; DNA damage response; TopBP1; E1; E2; ATM (ataxia-telangiectasia mutated); ATR (ataxia telangiectasia and Rad3 related); DNA damage signaling; cervical cancer; head and neck cancer; homologous recombination; MRN (Mre11-Rad50-Nbs1)
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Bristol, M.L.; Das, D.; Morgan, I.M. Why Human Papillomaviruses Activate the DNA Damage Response (DDR) and How Cellular and Viral Replication Persists in the Presence of DDR Signaling. Viruses 2017, 9, 268.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top