Activation of hypoxia-inducible factor 1 by Human Papillomavirus Oncoproteins

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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 VEGF. Both HPV E6 and E7 were able independently to enhance induction of HIF-1α upon DFO treatment. Our studies further indicate that HPV31 E7 associates with both HIF-1α and p53 in cells, and this association results in reduced interaction of the HIF-1α/p53 complex with MDM2. These findings shed light on mechanisms by which HPV contributes to angiogenesis both in benign cervical lesions and in cervical cancers and describes a novel role of the E7 oncogene in the virus-host interaction.