ArticleJournal of cell science2022
TRF2 inhibition rather than telomerase disruption drives CD4T cell dysfunction during chronic viral infection.
Article in Journal of cell science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The trial behind it
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Nebivolol prevents exhausted T cells and enhances cytotoxicity against MCF-7 breast cancer cells in a β2-adrenergic receptor-dependent manner.Clinical and experimental immunology · 2026Article
- Autophagy, telomerase, and endothelial dysfunction in COVID-19-induced cardiac injury: an evidence-graded genetic and epigenetic synthesis.Frontiers in cardiovascular medicine · 2026Review
- miR-23a-mediated TRF2 repression in CD4 T cells from PLWH.Molecular immunology · 2025Article
- Pan‑cancer analysis of the oncogenic role of telomeric repeat binding factor 2 (TERF2) in human tumors and in vitro validation in gastric cancer by TERF2 knockdown.Discover oncology · 2025Article
- Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells.Acta pharmacologica Sinica · 2024Article
- Circulating GDF-15: a biomarker for metabolic dysregulation and aging in people living with HIV.Frontiers in aging · 2024Article
- ROS-Induced Mitochondrial Dysfunction in CD4 T Cells from ART-Controlled People Living with HIV.Viruses · 2023Article
- Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
We investigated the role of telomerase and telomere repeat-binding factor 2 (TRF2 or TERF2) in T-cell dysfunction in chronic viral infection. We found that the expression and activity of telomerase in CD4+ T (CD4T) cells from patients with hepatitis C virus (HCV) infections or people living with HIV (PLWH) were intact, but TRF2 expression was significantly inhibited at the post-transcriptional level, suggesting that TRF2 inhibition is responsible for the CD4T cell dysfunction observed during chronic viral infection. Silencing TRF2 expression in CD4T cells derived from healthy subjects induced telomeric DNA damage and CD4T cell dysfunction without affecting telomerase activity or translocation - similar to what we observed in CD4T cells from HCV patients and PLWH. These findings indicate that premature T-cell aging and dysfunction during chronic HCV or HIV infection are primarily caused by chronic immune stimulation and T-cell overactivation and/or proliferation that induce telomeric DNA damage due to TRF2 inhibition, rather than telomerase disruption. This study suggests that restoring TRF2 presents a novel approach to prevent telomeric DNA damage and premature T-cell aging, thus rejuvenating T-cell functions during chronic viral infection.
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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.