Journal article
Activation of the Oxidative Stress Pathway by HIV-1 Vpr Leads to Induction of Hypoxia-inducible Factor 1{alpha} Expression
The Journal of biological chemistry, v 284(17), pp 11364-11373
24 Apr 2009
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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-1{alpha} 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-1{alpha}. Our results show that Vpr induces reactive oxygen species by increasing H sub(2)O sub(2) production, which can contribute to HIF-1{alpha} accumulation. Interestingly, increased levels of HIF-1{alpha} 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-1{alpha} 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.
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Details
- Title
- Activation of the Oxidative Stress Pathway by HIV-1 Vpr Leads to Induction of Hypoxia-inducible Factor 1{alpha} Expression
- Creators
- Satish Deshmane - Temple UniversityRuma Mukerjee - Temple UniversityShongshan Fan - Temple UniversityLuis Del Valle - Temple UniversityCarine Michiels - University of NamurThersa Sweet - Temple UniversityInna Rom - Temple UniversityKamel Khalili - Temple UniversityJay Rappaport - Temple UniversityShohreh Amini - Temple UniversityBassel Sawaya - Temple University
- Publication Details
- The Journal of biological chemistry, v 284(17), pp 11364-11373
- Publisher
- ASBMB Publications / Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Epidemiology and Biostatistics
- Web of Science ID
- WOS:000265494500041
- Scopus ID
- 2-s2.0-66449137818
- Other Identifier
- 991021448164504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology