ArticleThe Journal of cell biology2014
Casp8p41 generated by HIV protease kills CD4 T cells through direct Bak activation.
Erratum issuedOpen access · bronzeAbstract read
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Article in The Journal of cell biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.
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25citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Two or Three? Clinical and Proteomic Perspectives on Dolutegravir/Lamivudine Versus Bictegravir/Emtricitabine/Tenofovir Alafenamide as Initial HIV Treatment.Open forum infectious diseases · 2025Trial
- HIV-1 infection does not confer intrinsic resistance to cell death induced by cytotoxic T lymphocytes.bioRxiv : the preprint server for biology · 2026Article
- HIV-Induced Apoptosis: Host Defense and Viral Strategy.Biology · 2025Review
- Venetoclax, alone and in combination with the BH3 mimetic S63845, depletes HIV-1 latently infected cells and delays rebound in humanized mice.Cell reports. Medicine · 2023Article
- Clearance of HIV-1 or SIV reservoirs by promotion of apoptosis and inhibition of autophagy: Targeting intracellular molecules in cure-directed strategies.Journal of leukocyte biology · 2022Review
- So Pathogenic or So What?-A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research.Viruses · 2022Review
- Prime, shock and kill: BCL-2 inhibition for HIV cure.Frontiers in immunology · 2022Review
- Single center, open label dose escalating trial evaluating once weekly oral ixazomib in ART-suppressed, HIV positive adults and effects on HIV reservoir size in vivo.EClinicalMedicine · 2021Article
- The Combination of Venetoclax and Ixazomib Selectively and Efficiently Kills HIV-Infected Cell Lines but Has Unacceptable Toxicity in Primary Cell Models.Journal of virology · 2021Article
- Reactivating latent HIV with PKC agonists induces resistance to apoptosis and is associated with phosphorylation and activation of BCL2.PLoS pathogens · 2020Article
- Mechanisms of Human Immunodeficiency Virus-Associated Lymphocyte Regulated Cell Death.AIDS research and human retroviruses · 2020Review
- The involvement of regulated cell death forms in modulating the bacterial and viral pathogenesis.International review of cell and molecular biology · 2020Review
- The Role of the BCL-2 Family of Proteins in HIV-1 Pathogenesis and Persistence.Clinical microbiology reviews · 2019Review
- TRAILshort Protects against CD4 T Cell Death during Acute HIV Infection.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- HIV Protease-Generated Casp8p41, When Bound and Inactivated by Bcl2, Is Degraded by the Proteasome.Journal of virology · 2018Article
- Article
- Getting the "Kill" into "Shock and Kill": Strategies to Eliminate Latent HIV.Cell host & microbe · 2018Review
- HIV-infected macrophages and microglia that survive acute infection become viral reservoirs by a mechanism involving Bim.Scientific reports · 2017Article
- Maintenance of the HIV Reservoir Is Antagonized by Selective BCL2 Inhibition.Journal of virology · 2017Article
- Increasing procaspase 8 expression using repurposed drugs to induce HIV infected cell death in ex vivo patient cells.PloS one · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 3 institutions in 1 country.
Amy M SainskiDepartment of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294 Department of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294.
Haiming DaiDepartment of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294.
Sekar NatesampillaiDepartment of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294.
Yuan-Ping PangDepartment of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294.
Gary D BrenDepartment of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294.
Nathan W CumminsDepartment of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294.
Cristina CorreiaDepartment of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294.
X Wei MengDepartment of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294 Department of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294.
James E TararaDepartment of Biochemistry and Molecular Biology and Department of Molecular Medicine, Mayo Clinic, Rochester MN 55905.
Marina Ramirez-AlvaradoDepartment of Biochemistry and Molecular Biology and Department of Molecular Medicine, Mayo Clinic, Rochester MN 55905.
David J KatzmannDepartment of Biochemistry and Molecular Biology and Department of Molecular Medicine, Mayo Clinic, Rochester MN 55905.
Christina OchsenbauerDepartment of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294.
John C KappesDepartment of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294.
Scott H KaufmannDepartment of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294 Department of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294 Kaufmann.Scott@Mayo.edu Badley.Andrew@Mayo.edu.
Andrew D BadleyDepartment of Molecular Pharmacology and Experiment Therapeutics, Division of Oncology Research, Division of Infectious Diseases, and Department of Medicine, University of Alabama, Birmingham, AL 35294 Department of Biochemistry and Molecular Biology and Department of Molecular Medicine, Mayo Clinic, Rochester MN 55905 Kaufmann.Scott@Mayo.edu Badley.Andrew@Mayo.edu.
University of Alabama at Birmingham · USOffice of Infectious Diseases · USMayo Clinic in Arizona · US
Funding
Virology CoreP30AI027767 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI OLAF KUTSCH · 1988 to 2026
$84.1MPrime shock and kill for HIV erradicationR01AI110173 · NIAID · MAYO CLINIC ROCHESTER · PI BADLEY, ANDREW D · 2014 to 2024
$6.9MMayo Clinic Center for Translational Science ActivitiesKL2TR000136 · NCATS · MAYO CLINIC ROCHESTER · PI KHOSLA, SUNDEEP · 2012 to 2015
$6.6MPredoctoral Training Program in Molecular PharmacologyT32GM072474 · NIGMS · MAYO CLINIC ROCHESTER · PI KARNITZ, LARRY M · 2005 to 2020
$2.4MAnticancer drug-induced BH3-only protein.Bak interactionsR01CA166741 · NCI · MAYO CLINIC ROCHESTER · PI KAUFMANN, SCOTT H · 2012 to 2016
$1.6MEnhancing control of HIV by inhibiting TRAILshortR56AI102959 · NIAID · MAYO CLINIC ROCHESTER · PI BADLEY, ANDREW D · 2013 to 2013
$540kNCATS NIH HHS KL2 TR000136NCI NIH HHS R01 CA166741NIAID NIH HHS P30 AI027767NIAID NIH HHS R01 AI110173NIAID NIH HHS R56 AI102959NIGMS NIH HHS T32 GM072474
Abstract
Previous studies have shown that human immunodeficiency virus (HIV) protease cleaves procaspase 8 to a fragment, termed Casp8p41, that lacks caspase activity but nonetheless contributes to T cell apoptosis. Herein, we show that Casp8p41 contains a domain that interacts with the BH3-binding groove of pro-apoptotic Bak to cause Bak oligomerization, Bak-mediated membrane permeabilization, and cell death. Levels of active Bak are higher in HIV-infected T cells that express Casp8p41. Conversely, targeted mutations in the Bak-interacting domain diminish Bak binding and Casp8p41-mediated cell death. Similar mutations in procaspase 8 impair the ability of HIV to kill infected T cells. These observations support a novel paradigm in which HIV converts a normal cellular constituent into a direct activator that functions like a BH3-only protein.
Indexed as
ApoptosisAmino Acid Sequencebcl-2 Homologous Antagonist-Killer ProteinCaspase 8CD4-Positive T-LymphocytesHEK293 CellsHIV-1HIV ProteaseHumansJurkat CellsMolecular Sequence DataMutation, MissenseProtein BindingProtein Interaction Domains and MotifsProtein MultimerizationProteolysisBAK1 protein, humanbcl-2 Homologous Antagonist-Killer ProteinCASP8 protein, humanCaspase 8HIV Protease
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