ArticleNature2013
HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 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.
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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
137 citing papers in PubMed, 1 synthesis or guideline pooled it, 222 citations in OpenAlex.
- Safety and efficacy of fecal microbiota transplantation for viral diseases: A systematic review of clinical trials.PloS one · 2024Pooled it
- Non-integrase mechanisms for dolutegravir resistance.Retrovirology · 2026Review
- Roles of the cGAS-STING signaling pathway in viral latency.Journal of virology · 2026Review
- Elimination of Human Immunodeficiency Virus Reservoirs Harboring Intact Proviruses.The Journal of infectious diseases · 2026Article
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- Helminth Coinfections Modulate Disease Dynamics and Vaccination Success in the Era of Emerging Infectious Diseases.Vaccines · 2025Review
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- Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation.Nature communications · 2024Article
- Epistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors.Science advances · 2024Article
- HIV Expression in Infected T Cell Clones.Viruses · 2024Review
- HIV-associated neurocognitive disorder: key implications of the microbiota-gut-brain axis.Frontiers in microbiology · 2024Review
- TBC1D15 deficiency protects against doxorubicin cardiotoxicityActa pharmaceutica Sinica. B · 2023Article
- PSGL-1, a Strategic Biomarker for Pathological Conditions in HIV Infection: A Hypothesis Review.Viruses · 2023Review
- Analysis of the Contribution of 6-mer Seed Toxicity to HIV-1-Induced Cytopathicity.Journal of virology · 2023Article
- Both ATM and DNA-PK Are the Main Regulators of HIV-1 Post-Integrational DNA Repair.International journal of molecular sciences · 2023Article
- Tuberculosis and COVID-19 in the elderly: factors driving a higher burden of disease.Frontiers in immunology · 2023Review
- 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
- Genosensors as an alternative diagnostic sensing approaches for specific detection of virus species: A review of common techniques and outcomes.Trends in analytical chemistry : TRAC · 2022Review
- Rapid Loss of CD4 T Cells by Pyroptosis during Acute SIV Infection in Rhesus Macaques.Journal of virology · 2022Article
- Identification of an integrase-independent pathway of retrotransposition.Science advances · 2022Article
77 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Human immunodeficiency virus-1 (HIV-1) has infected more than 60 million people and caused nearly 30 million deaths worldwide, ultimately the consequence of cytolytic infection of CD4(+) T cells. In humans and in macaque models, most of these cells contain viral DNA and are rapidly eliminated at the peak of viraemia, yet the mechanism by which HIV-1 induces helper T-cell death has not been defined. Here we show that virus-induced cell killing is triggered by viral integration. Infection by wild-type HIV-1, but not an integrase-deficient mutant, induced the death of activated primary CD4 lymphocytes. Similarly, raltegravir, a pharmacologic integrase inhibitor, abolished HIV-1-induced cell killing both in cell culture and in CD4(+) T cells from acutely infected subjects. The mechanism of killing during viral integration involved the activation of DNA-dependent protein kinase (DNA-PK), a central integrator of the DNA damage response, which caused phosphorylation of p53 and histone H2AX. Pharmacological inhibition of DNA-PK abolished cell death during HIV-1 infection in vitro, suggesting that processes which reduce DNA-PK activation in CD4 cells could facilitate the formation of latently infected cells that give rise to reservoirs in vivo. We propose that activation of DNA-PK during viral integration has a central role in CD4(+) T-cell depletion, raising the possibility that integrase inhibitors and interventions directed towards DNA-PK may improve T-cell survival and immune function in infected individuals.
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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.