Regulation of the life cycle of HPVs by differentiation and the DNA damage response

Shiyuan Hong, Laimonis A. Laimins*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

38 Scopus citations

Abstract

HPVs are the causative agents of cervical and other anogenital cancers. HPVs infect stratified epithelia and link their productive life cycles to cellular differentiation. Low levels of viral genomes are stably maintained in undifferentiated cells and productive replication or amplification is restricted to differentiated suprabasal cells. Amplification is dependent on the activation of the ATM DNA damage factors that are recruited to viral replication centers and inhibition of this pathway blocks productive replication. The STAT-5 protein appears to play a critical role in mediating activation of the ATM pathway in HPV-positive cells. While HPVs need to activate the DNA damage pathway for replication, cervical cancers contain many genomic alterations suggesting that this pathway is circumvented during progression to malignancy.

Original languageEnglish (US)
Pages (from-to)1547-1557
Number of pages11
JournalFuture Microbiology
Volume8
Issue number12
DOIs
StatePublished - Dec 2013

Keywords

  • ATM
  • CHK2
  • DNA damage
  • STAT-5
  • amplification
  • differentiation
  • papillomaviruses
  • replication foci

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

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