ArticleCell discovery2018
Insufficiency of DNA repair enzyme ATM promotes naive CD4 T-cell loss in chronic hepatitis C virus infection.
Article in Cell discovery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
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Who cites it
27 citing papers in PubMed, 56 citations in OpenAlex.
- Increased genomic instability following treatment with direct acting anti-hepatitis C virus drugs.EBioMedicine · 2018Trial
- Rapamycin Exerts Its Geroprotective Effects in the Ageing Human Immune System by Enhancing Resilience Against DNA Damage.Aging cell · 2026Article
- Persistent Low Anti-HIV Neutralizing Antibody Titers in HIV/HCV Coinfection Despite HCV Cure: A 5-Year Longitudinal Analysis.Vaccines · 2025Article
- Tyrosine kinase signaling-independent MET-targeting with CAR-T cells.Journal of translational medicine · 2023Article
- ROS-Induced Mitochondrial Dysfunction in CD4 T Cells from ART-Controlled People Living with HIV.Viruses · 2023Article
- The central role of DNA damage in immunosenescence.Frontiers in aging · 2023Review
- TRF2 inhibition rather than telomerase disruption drives CD4T cell dysfunction during chronic viral infection.Journal of cell science · 2022Article
- SARS-CoV-2 infection in patients with inborn errors of immunity due to DNA repair defects.Acta biochimica et biophysica Sinica · 2022Review
- Longitudinal Immune Profiling of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection in a Solid Organ Transplant Recipient.The Journal of infectious diseases · 2022Article
- Mitochondrial topoisomerase 1 inhibition induces topological DNA damage and T cell dysfunction in patients with chronic viral infection.Frontiers in cellular and infection microbiology · 2022Article
- Single-Cell Sequencing of Immune Cells in Human Aortic Dissection Tissue Provides Insights Into Immune Cell Heterogeneity.Frontiers in cardiovascular medicine · 2022Article
- Selective oxidative stress induces dual damage to telomeres and mitochondria in human T cells.Aging cell · 2021Article
- Immune Activation Induces Telomeric DNA Damage and Promotes Short-Lived Effector T Cell Differentiation in Chronic HCV Infection.Hepatology (Baltimore, Md.) · 2021Article
- Longitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient.Research square · 2021Article
- Naïve CD4+ T Cell Lymphopenia and Apoptosis in Chronic Hepatitis C Virus Infection Is Driven by the CD31+ Subset and Is Partially Normalized in Direct-Acting Antiviral Treated Persons.Frontiers in immunology · 2021Article
- Mitochondrial Functions Are Compromised in CD4 T Cells From ART-Controlled PLHIV.Frontiers in immunology · 2021Article
- Oxidative Stress Induces Mitochondrial Compromise in CD4 T Cells From Chronically HCV-Infected Individuals.Frontiers in immunology · 2021Article
- Telomeric injury by KML001 in human T cells induces mitochondrial dysfunction through the p53-PGC-1α pathway.Cell death & disease · 2020Article
- Telomere and ATM Dynamics in CD4 T-Cell Depletion in Active and Virus-Suppressed HIV Infections.Journal of virology · 2020Article
- A Matter of Life or Death: Productively Infected and Bystander CD4 T Cells in Early HIV Infection.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
T cells have a crucial role in viral clearance and vaccine response; however, the mechanisms regulating their responses to viral infections or vaccinations remain elusive. In this study, we investigated T-cell homeostasis, apoptosis, DNA damage, and repair machineries in a large cohort of subjects with hepatitis C virus (HCV) infection. We found that naive CD4 T cells in chronically HCV-infected individuals (HCV T cells) were significantly reduced compared with age-matched healthy subjects. In addition, HCV T cells were prone to apoptosis and DNA damage, as evidenced by increased 8-oxoguanine expression and γH2AX/53BP1-formed DNA damage foci-hallmarks of DNA damage responses. Mechanistically, the activation of DNA repair enzyme ataxia telangiectasia mutated (ATM) was dampened in HCV T cells. ATM activation was also diminished in healthy T cells exposed to ATM inhibitor or to HCV (core protein) that inhibits the phosphoinositide 3 kinase pathway, mimicking the biological effects in HCV T cells. Importantly, ectopic expression of ATM was sufficient to repair the DNA damage, survival deficit, and cell dysfunctions in HCV T cells. Our results demonstrate that insufficient DNA repair enzyme ATM leads to increased DNA damage and renders HCV T cells prone to apoptotic death, which contribute to the loss of naive T cells in HCV infection. Our study reveals a novel mechanism for T-cell dysregulation and viral persistence, providing a new strategy to improve immunotherapy and vaccine responses against human viral diseases.
Identifiers
What OpenQuestion holds
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.