ArticleJournal of immunology (Baltimore, Md. : 1950)2008
Tat-induced FOXO3a is a key mediator of apoptosis in HIV-1-infected human CD4+ T lymphocytes.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 58 citations in OpenAlex.
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- DRAM triggers lysosomal membrane permeabilization and cell death in CD4(+) T cells infected with HIV.PLoS pathogens · 2013Trial
- HIV-1 infection does not confer intrinsic resistance to cell death induced by cytotoxic T lymphocytes.bioRxiv : the preprint server for biology · 2026Article
- ATF4 Signaling in HIV-1 Infection: Viral Subversion of a Stress Response Transcription Factor.Biology · 2024Review
- Overcoming Taxane Resistance: Preclinical and Phase 1 Studies of Relacorilant, a Selective Glucocorticoid Receptor Modulator, with Nab-Paclitaxel in Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Selective BCL-XJournal of virology · 2021Article
- Pathogens and Carcinogenesis: A Review.Biology · 2021Review
- The Interplay of HIV and Autophagy in Early Infection.Frontiers in microbiology · 2021Review
- RETRACTED: Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells.International journal of molecular sciences · 2020Article
- Genome-Wide Characterization of Host Transcriptional and Epigenetic Alterations During HIV Infection of T Lymphocytes.Frontiers in immunology · 2020Article
- The Role of the BCL-2 Family of Proteins in HIV-1 Pathogenesis and Persistence.Clinical microbiology reviews · 2019Review
- Article
- Genetic variation and function of the HIV-1 Tat protein.Medical microbiology and immunology · 2019Review
- Article
- Engineering modular intracellular protein sensor-actuator devices.Nature communications · 2018Article
- The transcriptome of HIV-1 infected intestinal CD4+ T cells exposed to enteric bacteria.PLoS pathogens · 2017Article
- Brief Report: Coordinated Modulation of Circulating miR-21 in HIV, HIV-Associated Pulmonary Arterial Hypertension, and HIV/Hepatitis C Virus Coinfection.Journal of acquired immune deficiency syndromes (1999) · 2015Article
- HTLV-1 Tax-mediated inhibition of FOXO3a activity is critical for the persistence of terminally differentiated CD4+ T cells.PLoS pathogens · 2014Article
- Noxa in rheumatic diseases: present understanding and future impact.Rheumatology (Oxford, England) · 2014Review
- Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The high mutation rate of HIV is linked to the generation of viruses expressing proteins with altered function whose impact on disease progression is unknown. We investigated how HIV-1 viruses lacking Env, Vpr, and Nef affect CD4(+) T cell survival. We found that in the absence of these proteins, HIV-1-infected CD4(+) primary T cells progress to the G(0) phase of the cell cycle and to cell death, indicating that viruses expressing inactive forms of these proteins can contribute to the CD4(+) T cell decline as the wild-type virus, suggesting that other HIV proteins are responsible for inducing apoptosis. Apoptosis in these cells is triggered by the alteration of the Egr1-PTEN-Akt (early growth response-1/phosphate and tensin homolog deleted on chromosome 10/Akt) and p53 pathways, which converge on the FOXO3a (Forkhead box transcription factor O class 3a) transcriptional activator. The FOXO3a target genes Fas ligand and TRAIL, involved in the extrinsic apoptotic pathway, and PUMA, Noxa, and Bim, which are part of the intrinsic apoptotic pathway, were also up-regulated, indicating that HIV infection leads to apoptosis by the engagement of multiple apoptotic pathways. RNAi-mediated knockdown of Egr1 and FOXO3a resulted in reduced apoptosis in HIV-infected HeLa and CD4(+) T cells, providing further evidence for their critical role in HIV-induced apoptosis and G(0) arrest. We tested the possibility that Tat is responsible for the T cell apoptosis observed with these mutant viruses. The induction of Egr1 and FOXO3a and its target genes was observed in Jurkat cells transduced by Tat alone. Tat-dependent activation of the Egr1-PTEN-FOXO3a pathway provides a mechanism for HIV-1-associated CD4(+) T cell death.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.