Hypoxia-specific stabilization of HIF-1alpha by human papillomaviruses

Mitsuhiro Nakamura, Jason M. Bodily, Melanie Beglin, Satoru Kyo, Masaki Inoue, Laimonis A. Laimins*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Human papillomaviruses (HPV) are the causative agents of cervical cancer and have been shown to increase expression of pro-angiogenic factors from infected cells. Many angiogenic factors are regulated by hypoxia inducible factor 1α (HIF-1α). We investigated whether HPV31 affects the levels of HIF-1α under normal and hypoxic conditions. Our studies indicate that cells containing complete HPV31 genomes showed enhanced levels of HIF-1α upon treatment with the hypoxia mimic DFO, which resulted from protein stabilization and led to increased expression of some but not all HIF-1α target genes. Both HPV E6 and E7 were able independently to enhance induction of HIF-1α upon DFO treatment. Enhancement of HIF-1α stability was not restricted to high-risk HPV types, as HPV11, a low risk HPV type, mediated a similar effect. These findings shed light on mechanisms by which HPV contributes to angiogenesis both in benign cervical lesions and in cervical cancers.

Original languageEnglish (US)
Pages (from-to)442-448
Number of pages7
JournalVirology
Volume387
Issue number2
DOIs
StatePublished - May 10 2009

Keywords

  • Angiogenesis
  • Carbonic anhydrase (CAIX)
  • Deferoxamine mesylate (DFO)
  • Hypoxia
  • Hypoxia inducible factor-1 (HIF-1)
  • Keratinocytes
  • Papillomaviruses (HPV)
  • Vascular endothelial growth factor (VEGF)

ASJC Scopus subject areas

  • Virology

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