ArticleImmunity & ageing : I & A2019
Topological DNA damage, telomere attrition and T cell senescence during chronic viral infections.
Article in Immunity & ageing : I & A, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 32 citations in OpenAlex.
- Hematopoietic Aging and Leukemia: Mechanistic and Therapeutic Insights.International journal of molecular sciences · 2026Review
- Diversity of oxidative stress and senescence phenotypes induced by chemotherapeutic agents in HUVECs.Scientific reports · 2025Article
- Identification and validation of genes related to stem cells and telomere maintenance mechanisms as biomarkers for breast cancer.Frontiers in immunology · 2025Article
- Isolation and detection of DNA-protein crosslinks in mammalian cells.Nucleic acids research · 2024Article
- ROS-Induced Mitochondrial Dysfunction in CD4 T Cells from ART-Controlled People Living with HIV.Viruses · 2023Article
- Review
- Cellular and molecular insights into incomplete immune recovery in HIV/AIDS patients.Frontiers in immunology · 2023Review
- The central role of DNA damage in immunosenescence.Frontiers in aging · 2023Review
- Immunosenescence of T cells: a key player in rheumatoid arthritis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- 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
- Immunosenescence in atherosclerosis: A role for chronic viral infections.Frontiers in immunology · 2022Review
- Occult Infection with Hepatitis C Virus: Looking for Clear-Cut Boundaries and Methodological Consensus.Journal of clinical medicine · 2021Review
- Selective oxidative stress induces dual damage to telomeres and mitochondria in human T cells.Aging cell · 2021Article
- Decreased ATM Function Causes Delayed DNA Repair and Apoptosis in Common Variable Immunodeficiency Disorders.Journal of clinical immunology · 2021Article
- Critical roles of Rad54 in tolerance to apigenin-induced Top1-mediated DNA damage.Experimental and therapeutic medicine · 2021Article
- Review
- 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
- Long Non-coding RNA GAS5 Regulates T Cell Functions via miR21-Mediated Signaling in People Living With HIV.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
backgroundT cells play a key role in controlling viral infections; however, the underlying mechanisms regulating their functions during human viral infections remain incompletely understood. Here, we used CD4 T cells derived from individuals with chronic viral infections or healthy T cells treated with camptothecin (CPT) - a topoisomerase I (Top 1) inhibitor - as a model to investigate the role of DNA topology in reprogramming telomeric DNA damage responses (DDR) and remodeling T cell functions.
resultsWe demonstrated that Top 1 protein expression and enzyme activity were significantly inhibited, while the Top 1 cleavage complex (TOP1cc) was trapped in genomic DNA, in T cells derived from individuals with chronic viral (HCV, HBV, or HIV) infections. Top 1 inhibition by CPT treatment of healthy CD4 T cells caused topological DNA damage, telomere attrition, and T cell apoptosis or dysfunction via inducing Top1cc accumulation, PARP1 cleavage, and failure in DNA repair, thus recapitulating T cell dysregulation in the setting of chronic viral infections. Moreover, T cells from virally infected subjects with inhibited Top 1 activity were more vulnerable to CPT-induced topological DNA damage and cell apoptosis, indicating an important role for Top 1 in securing DNA integrity and cell survival.
conclusionThese findings provide novel insights into the molecular mechanisms for immunomodulation by chronic viral infections via disrupting DNA topology to induce telomeric DNA damage, T cell senescence, apoptosis and dysfunction. As such, restoring the impaired DNA topologic machinery may offer a new strategy for maintaining T cell function against human viral diseases.
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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.