ArticleThe Journal of biological chemistry2013
The presence of HIV-1 Tat protein second exon delays fas protein-mediated apoptosis in CD4+ T lymphocytes: a potential mechanism for persistent viral production.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04263207 (Observational Study for the Evaluation of the Role of HIV-1 Tat Protein and Anti-Tat Immune Response in Peripheral Blood HIV Reservoir Dynamics), which is not on this map. Cited by 46 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Observational Study for the Evaluation of the Role of HIV-1 Tat Protein and Anti-Tat Immune Response in Peripheral Blood HIV Reservoir Dynamics
Who cites it
46 citing papers in PubMed, 59 citations in OpenAlex.
- Blocking Host Factors IAP and DDX3 Activates HIV-1 Transcription and Increases Apoptosis Sensitivity of HIV-1 Infected Cells.Pathogens (Basel, Switzerland) · 2026Article
- HIV-1 infection does not confer intrinsic resistance to cell death induced by cytotoxic T lymphocytes.bioRxiv : the preprint server for biology · 2026Article
- Methaneseleninic acid, a circadian-modulating agent, reactivates latent HIV-1 infection without cellular activation or proliferation.Journal of virology · 2026Article
- Selective reactivation of latent HIV using CyclinT1-Tat-containing virus-like particles.Virology · 2026Article
- A novel antiviral strategy by disrupting the equilibrium of virus-host calcium homeostasis.Current opinion in virology · 2026Review
- HIV-1 Tat and gp120 as key drivers of neurodegeneration in the central nervous system.Frontiers in microbiology · 2026Review
- The HIV-1 Vpr R77Q mutant alters host apoptotic gene regulation in CD4+ T cells.Frontiers in cellular and infection microbiology · 2026Article
- Resist to persist: resistance of the HIV reservoir to immune-mediated clearance.Current opinion in HIV and AIDS · 2025Review
- Intracellular HIV-1 Tat regulator induces epigenetic changes in the DNA methylation landscape.Frontiers in immunology · 2025Article
- HIV-Tat upregulates the expression of senescence biomarkers in CD4Frontiers in immunology · 2025Article
- SMAC mimetics sensitize HIV-infected cells to oncolytic virus-mediated death.Frontiers in immunology · 2025Article
- Role of HIV-1 Tat Protein Interactions with Host Receptors in HIV Infection and Pathogenesis.International journal of molecular sciences · 2024Review
- Features of Tat Protein in HIV-1 Sub-Subtype A6 Variants Circulating in the Moscow Region, Russia.Viruses · 2023Article
- HIV-1 Tat Upregulates TREM1 Expression in Human Microglia.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Aloe-emodin inhibits African swine fever virus replication by promoting apoptosis via regulating NF-κB signaling pathway.Virology journal · 2023Article
- Cytosine-phosphate-guanine oligodeoxynucleotides regulate the cell cycle, apoptosis, and steroidogenesis of mouse ovarian granulosa cells by targeting inhibin alpha (1 ~ 32) fragments.In vitro cellular & developmental biology. Animal · 2022Article
- Interaction between the Hepatitis B Virus and Cellular FLIP Variants in Viral Replication and the Innate Immune System.Viruses · 2022Review
- Role of Apoptosis in HIV Pathogenesis.Advances in virology · 2022Review
- New insights into pathogenesis point to HIV-1 Tat as a key vaccine target.Archives of virology · 2021Review
- SMAC Mimetics as Therapeutic Agents in HIV Infection.Frontiers in immunology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HIV-1 replication is efficiently controlled by the regulator protein Tat (101 amino acids) and codified by two exons, although the first exon (1-72 amino acids) is sufficient for this process. Tat can be released to the extracellular medium, acting as a soluble pro-apoptotic factor in neighboring cells. However, HIV-1-infected CD4(+) T lymphocytes show a higher resistance to apoptosis. We observed that the intracellular expression of Tat delayed FasL-mediated apoptosis in both peripheral blood lymphocytes and Jurkat cells, as it is an essential pathway to control T cell homeostasis during immune activation. Jurkat-Tat cells showed impairment in the activation of caspase-8, deficient release of mitochondrial cytochrome c, and delayed activation of both caspase-9 and -3. This protection was due to a profound deregulation of proteins that stabilized the mitochondrial membrane integrity, such as heat shock proteins, prohibitin, or nucleophosmin, as well as to the up-regulation of NF-κB-dependent anti-apoptotic proteins, such as BCL2, c-FLIPS, XIAP, and C-IAP2. These effects were observed in Jurkat expressing full-length Tat (Jurkat-Tat101) but not in Jurkat expressing the first exon of Tat (Jurkat-Tat72), proving that the second exon, and particularly the NF-κB-related motif ESKKKVE, was necessary for Tat-mediated protection against FasL apoptosis. Accordingly, the protection exerted by Tat was independent of its function as a regulator of both viral transcription and elongation. Moreover, these data proved that HIV-1 could have developed strategies to delay FasL-mediated apoptosis in infected CD4(+) T lymphocytes through the expression of Tat, thus favoring the persistent replication of HIV-1 in infected T cells.
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Registered trials
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