Evidence map›Paper›PMID 35660868›Full record

ArticleJournal of cell science2022

TRF2 inhibition rather than telomerase disruption drives CD4T cell dysfunction during chronic viral infection.

Lam Ngoc Thao Nguyen, Lam Nhat Nguyen, Juan Zhao, Madison Schank, Xindi Dang, Dechao Cao, Sushant Khanal, Xiao Y Wu, Yi Zhang, Jinyu Zhang and 5 more

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 1 institution in 1 country.

Lam Ngoc Thao NguyenCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Lam Nhat NguyenCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Juan ZhaoCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Madison SchankCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Xindi DangCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Dechao CaoCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Sushant KhanalCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Xiao Y WuCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Yi ZhangCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Jinyu ZhangCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Shunbin NingCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Ling WangCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Mohamed El GazzarCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Jonathan P MoormanCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Zhi Q YaoCenter of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.ORCID 0000-0002-1848-1071
East Tennessee State University · US

Funding

Mitochondrial Dysfunction in Aging CD4 T cells in HIV-immune Non-responders.R15AG069544 · NIA · EAST TENNESSEE STATE UNIVERSITY · PI YAO, ZHI Q. · 2021 to 2023
$803k
Mechanism of telomere attrition and premature T cell aging during HIV infection.R15AG076370 · NIA · EAST TENNESSEE STATE UNIVERSITY · PI ZHAO, JUAN · 2022 to 2023
$704k
Multiuser Advanced Biosafe Flow CytometerS10OD021572 · OD · EAST TENNESSEE STATE UNIVERSITY · PI MOORMAN, JONATHAN P · 2017 to 2017
$553k
Dual specific gene editing drugs delivered by nanoparticles targeting HBV/HIV coinfectionR21AI157909 · NIAID · EAST TENNESSEE STATE UNIVERSITY · PI YAO, ZHI Q. · 2021 to 2022
$420k
Telomere loss and T cell aging in HBV vaccine response in HCV-infected individualI01BX004281 · VA · JAMES H QUILLEN VA MEDICAL CENTER · PI YAO, ZHI Q. · 2019 to 2022
–
COVID-19: Characterizing trained immune responses to COVID-19I01BX005428 · VA · JAMES H QUILLEN VA MEDICAL CENTER · PI MOORMAN, JONATHAN P · 2021 to 2022
–
Telomere attrition and T cell aging in vaccine failure during HIV infectionI01BX002670 · VA · JAMES H QUILLEN VA MEDICAL CENTER · PI YAO, ZHI Q. · 2016 to 2025
–
American Diabetes Association 7-20-COVID-149BLRD VA I01 BX002670BLRD VA I01 BX004281BLRD VA I01 BX005428BLRD VA IS1 BX003540NIAID NIH HHS R21 AI157909NIA NIH HHS R15 AG069544NIA NIH HHS R15 AG076370NIH HHS S10 OD021572U.S. Department of Defense PR170067U.S. Department of Veterans Affairs 1I01BX002670
6 · The paper itself

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.

Indexed as

CD4-Positive T-LymphocytesHIV InfectionsTelomeraseTelomeric Repeat Binding Protein 2DNA DamageHepacivirusHepatitis C, ChronicHumansTelomereTelomeraseTelomeric Repeat Binding Protein 2TERF2 protein, humanHCVHIVT-cell dysfunctionTelomeraseTelomere erosionTRF2

Identifiers

PMID35660868
PMCPMC9377711
OpenAlexW4281675646

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.