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Virology. 2009 May 10;387(2):442-8. doi: 10.1016/j.virol.2009.02.036. Epub 2009 Mar 24.

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

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1
Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine, Morton, Chicago, IL 60611, USA.

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 1alpha (HIF-1alpha). We investigated whether HPV31 affects the levels of HIF-1alpha under normal and hypoxic conditions. Our studies indicate that cells containing complete HPV31 genomes showed enhanced levels of HIF-1alpha upon treatment with the hypoxia mimic DFO, which resulted from protein stabilization and led to increased expression of some but not all HIF-1alpha target genes. Both HPV E6 and E7 were able independently to enhance induction of HIF-1alpha upon DFO treatment. Enhancement of HIF-1alpha 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.

PMID:
19321184
PMCID:
PMC2674135
DOI:
10.1016/j.virol.2009.02.036
[Indexed for MEDLINE]
Free PMC Article
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