ArticleCell death & disease2018
Inhibition of TRF2 accelerates telomere attrition and DNA damage in naïve CD4 T cells during HCV infection.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- [Research progress on cellular senescence and liver diseases].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- miR-23a-mediated TRF2 repression in CD4 T cells from PLWH.Molecular immunology · 2025Article
- Canonical and non-canonical functions of the non-coding RNA component (TERC) of telomerase complex.Cell & bioscience · 2025Review
- Senescence-like Phenotype After Chronic Exposure to Isoproterenol in Primary Quiescent Immune Cells.Biomolecules · 2024Article
- Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells.Acta pharmacologica Sinica · 2024Article
- Accelerated Neuroimmune Dysfunction in Aged HIV-1-Infected Humanized Mice.Pharmaceuticals (Basel, Switzerland) · 2024Article
- 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
- SMG6 regulates DNA damage and cell survival in Hippo pathway kinase LATS2-inactivated malignant mesothelioma.Cell death discovery · 2022Article
- TRF2 inhibition rather than telomerase disruption drives CD4T cell dysfunction during chronic viral infection.Journal of cell science · 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
- 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
- The Impact of HIV- and ART-Induced Mitochondrial Dysfunction in Cellular Senescence and Aging.Cells · 2021Review
- Oxidative Stress Induces Mitochondrial Compromise in CD4 T Cells From Chronically HCV-Infected Individuals.Frontiers in immunology · 2021Article
- Mitochondrial Functions Are Compromised in CD4 T Cells From ART-Controlled PLHIV.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
- The role of MDM2-p53 axis dysfunction in the hepatocellular carcinoma transformation.Cell death discovery · 2020Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
T cells play a crucial role in viral clearance and vaccine responses; however, the mechanisms that regulate their homeostasis during viral infections remain unclear. In this study, we investigated the machineries of T-cell homeostasis and telomeric DNA damage using a human model of hepatitis C virus (HCV) infection. We found that naïve CD4 T cells in chronically HCV-infected patients (HCV T cells) were significantly reduced due to apoptosis compared with age-matched healthy subjects (HSs). These HCV T cells were not only senescent, as demonstrated by overexpression of aging markers and particularly shortened telomeres; but also DNA damaged, as evidenced by increased dysfunctional telomere-induced foci (TIF). Mechanistically, the telomere shelterin protein, in particular telomeric repeat binding factor 2 (TRF2) that functions to protect telomeres from DNA damage, was significantly inhibited posttranscriptionally via the p53-dependent Siah-1a ubiquitination. Importantly, knockdown of TRF2 in healthy T cells resulted in increases in telomeric DNA damage and T-cell apoptosis, whereas overexpression of TRF2 in HCV T cells alleviated telomeric DNA damage and T-cell apoptosis. To the best of our knowledge, this is the first report revealing that inhibition of TRF2 promotes T-cell telomere attrition and telomeric DNA damage that accelerates T-cell senescent and apoptotic programs, which contribute to naïve T-cell loss during viral infection. Thus, restoring the impaired T-cell telomeric shelterin machinery may offer a new strategy to improve immunotherapy and vaccine response against human viral diseases.
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