ArticleJournal of virology2007
Commitment to apoptosis in CD4(+) T lymphocytes productively infected with human immunodeficiency virus type 1 is initiated by lysosomal membrane permeabilization, itself induced by the isolated expression of the viral protein Nef.
Article in Journal of virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- The Hitchhiker Guide to CD4Frontiers in immunology · 2021Pooled it
- 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
- Underlying Mechanism of Lysosomal Membrane Permeabilization in CNS Injury: A Literature Review.Molecular neurobiology · 2025Review
- The HN protein of Newcastle disease virus induces cell apoptosis through the induction of lysosomal membrane permeabilization.PLoS pathogens · 2024Article
- Spatial localization of cathepsins: Implications in immune activation and resolution during infections.Frontiers in immunology · 2022Review
- Crucial Role of Central Nervous System as a Viral Anatomical Compartment for HIV-1 Infection.Microorganisms · 2021Review
- Mechanisms of Human Immunodeficiency Virus-Associated Lymphocyte Regulated Cell Death.AIDS research and human retroviruses · 2020Review
- Cross-talk between microglia and neurons regulates HIV latency.PLoS pathogens · 2019Article
- The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques.The Journal of clinical investigation · 2018Article
- The Role of HIV Infection in Neurologic Injury.Brain sciences · 2017Review
- Inhibition of cholesterol metabolism underlies synergy between mTOR pathway inhibition and chloroquine in bladder cancer cells.Oncogene · 2016Article
- The role of lysosome in cell death regulation.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- PIG7 promotes leukemia cell chemosensitivity via lysosomal membrane permeabilization.Oncotarget · 2016Article
- Macrophage derived cystatin B/cathepsin B in HIV replication and neuropathogenesis.Current HIV research · 2014Review
- HIV integrase and the swan song of the CD4 T cells?Retrovirology · 2013Article
- Candida albicans secreted aspartic proteases 4-6 induce apoptosis of epithelial cells by a novel Trojan horse mechanism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- Dysregulation of macrophage-secreted cathepsin B contributes to HIV-1-linked neuronal apoptosis.PloS one · 2012Article
- HIV-1 Nef increases astrocyte sensitivity towards exogenous hydrogen peroxide.Virology journal · 2011Article
- Mitochondria and viruses.Mitochondrion · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary CD4(+) T lymphocytes, supporting in vitro human immunodeficiency virus type 1 (HIV-1) replication, are destined to die by apoptosis. We explored the initial molecular events that act upstream from mitochondrial dysfunction in CD4(+) T lymphocytes exposed to the HIV-1(LAI) strain. We tracked by immunofluorescence the cells expressing the p24 viral antigen and used Percoll density gradients to isolate a nonapoptotic CD4(+) T-cell subset with a high inner mitochondrial transmembrane potential (DeltaPsim) but no outer mitochondrial membrane (OMM) rupture. In most p24(+) (but not bystander p24(-)) cells of this subset, the lysosomes were undergoing limited membrane permeabilization, allowing the lysosomal efflux of cathepsins (Cat) to the cytosol. This was also induced by HIV-1 isolates from infected patients. Using pepstatin A to inhibit Cat-D enzymatic activity and Cat-D small interfering RNA to silence the Cat-D gene, we demonstrate that once released into the cytosol, Cat-D induces the conformational change of Bax and its insertion into the OMM. Inhibition of Cat-D activity/expression also conferred a transient survival advantage upon productively HIV-1-infected cells, indicating that Cat-D is an early death factor. The transfection of activated CD4(+) T lymphocytes with a Nef expression vector rapidly induced the permeabilization of lysosomes and the release of Cat-D, with these two events preceding OMM rupture. These results reveal a previously undocumented mechanism in which Nef acts as an internal cytopathic factor and strongly suggest that this viral protein may behave similarly in the context of productive HIV-1 infection in CD4(+) T lymphocytes.
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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.