Activation of the oxidative stress pathway by HIV-1 Vpr leads to induction of hypoxia-inducible factor 1α expression

Satish L. Deshmane, Ruma Mukerjee, Shongshan Fan, Luis Del Valle, Carine Michiels, Thersa Sweet, Inna Rom, Kamel Khalili, Jay Rappaport, Shohreh Amini, Bassel E. Sawaya

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs


The detection of biomarkers of oxidative stress in brain tissue and cerebrospinal fluid of patients with human immunodeficiency virus, type 1 (HIV)-associated dementia indicates the involvement of stress pathways in the neuropathogenesis of AIDS. Although the biological importance of oxidative stress on events involved in AIDS neuropathogenesis and the HIV-1 proteins responsible for oxidative stress remain to be elucidated, our results point to the activation of hypoxia-inducible factor 1 (HIF-1) upon HIV-1 infection and its elevation in brain cells of AIDS patients with dementia. HIF-1 is a transcription factor that is responsive to oxygen. Under hypoxic conditions, HIF-1α becomes stable and translocates to the nucleus where it dimerizes with aryl hydrocarbon receptor nuclear translocator and modulates gene transcription. Activation of HIF-1 can also be mediated by the HIV-1 accessory protein Vpr. In addition, cellular components, including reactive oxygen species, contribute to the induction of HIF-1α. Our results show that Vpr induces reactive oxygen species by increasing H2O2 production, which can contribute to HIF-1α accumulation. Interestingly, increased levels of HIF-1α stimulated HIV-1 gene transcription through HIF-1 association with HIV-1 long terminal repeat. These observations point to the existence of a positive feedback interplay between HIF-1α and Vpr and that, by inducing oxidative stress via activation of HIF-1, Vpr can induce HIV-1 gene expression and dysregulate multiple host cellular pathways. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

langue originaleAnglais
Pages (de - à)11364-11373
Nombre de pages10
journalJournal of Biological Chemistry
Numéro de publication17
Les DOIs
Etat de la publicationPublié - 2009

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