Impact of Replication Stress in Human Papillomavirus Pathogenesis

J Virol. 2019 Jan 4;93(2):e01012-17. doi: 10.1128/JVI.01012-17. Print 2019 Jan 15.

Abstract

The inactivation of critical cell cycle checkpoints by the human papillomavirus (HPV) oncoprotein E7 results in replication stress (RS) that leads to genomic instability in premalignant lesions. Intriguingly, RS tolerance is achieved through several mechanisms, enabling HPV to exploit the cellular RS response for viral replication and to facilitate viral persistence in the presence of DNA damage. As such, inhibitors of the RS response pathway may provide a novel approach to target HPV-associated lesions and cancers.

Keywords: ATR; DNA damage; cancer; genomic instability; papillomavirus; replication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Cycle Proteins / metabolism
  • DNA Replication
  • Genomic Instability*
  • Humans
  • Papillomaviridae / pathogenicity*
  • Papillomavirus E7 Proteins / metabolism*
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / virology
  • Virus Replication

Substances

  • Cell Cycle Proteins
  • Papillomavirus E7 Proteins