Evidence mapPaperPMID 39242776Full record

ArticleEMBO reports2024

HIV-1 Vpu induces neurotoxicity by promoting Caspase 3-dependent cleavage of TDP-43.

Jiaxin Yang, Yan Li, Huili Li, Haichen Zhang, Haoran Guo, Xiangyu Zheng, Xiao-Fang Yu, Wei Wei

Abstract read
In one paragraph

Article in EMBO reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
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

4 citing papers in PubMed.

  1. TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026
    Review
  2. Article
  3. Review
  4. Article
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

8 authors.

Jiaxin YangInstitute of Virology and AIDS Research, First Hospital, Jilin University, 130021, Changchun, Jilin, China.
Yan LiInstitute of Virology and AIDS Research, First Hospital, Jilin University, 130021, Changchun, Jilin, China.
Huili LiInstitute of Virology and AIDS Research, First Hospital, Jilin University, 130021, Changchun, Jilin, China.
Haichen ZhangDepartment of Neurology and Neuroscience Center, First Hospital, Jilin University, 130021, Changchun, Jilin, China.
Haoran GuoInstitute of Virology and AIDS Research, First Hospital, Jilin University, 130021, Changchun, Jilin, China.
Xiangyu ZhengDepartment of Neurology and Neuroscience Center, First Hospital, Jilin University, 130021, Changchun, Jilin, China.
Xiao-Fang YuCancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0000-0002-6104-3456
Wei WeiInstitute of Virology and AIDS Research, First Hospital, Jilin University, 130021, Changchun, Jilin, China. wwei6@jlu.edu.cn.ORCID http://orcid.org/0000-0003-4456-840X

Funding

Department of Science and Technology of Jilin Province () 20210101015JCMOST | National Natural Science Foundation of China (NSFC) 82172246MOST | National Natural Science Foundation of China (NSFC) 82372226MOST | NSFC | Excellent Young Scientists Fund (Young Scientists Fund) 32222005National Major Project for Infectious Disease Control and Prevention 2018ZX10731-101-001-016Open Project of Key Laboratory of Organ Regeneration and Transplantation, Ministry of Education, the Program for JLU Science and Technology Innovative Research Team 2017TD-08
6 · The paper itself

Abstract

Despite the efficacy of highly active antiretroviral therapy in controlling the incidence and mortality of AIDS, effective interventions for HIV-1-induced neurological damage and cognitive impairment remain elusive. In this study, we found that HIV-1 infection can induce proteolytic cleavage and aberrant aggregation of TAR DNA-binding protein 43 (TDP-43), a pathological protein associated with various severe neurological disorders. The HIV-1 accessory protein Vpu was found to be responsible for the cleavage of TDP-43, as ectopic expression of Vpu alone was sufficient to induce TDP-43 cleavage, whereas HIV-1 lacking Vpu failed to cleave TDP-43. Mechanistically, the cleavage of TDP-43 at Asp89 by HIV-1 relies on Vpu-mediated activation of Caspase 3, and pharmacological inhibition of Caspase 3 activity effectively suppressed the HIV-1-induced aggregation and neurotoxicity of TDP-43. Overall, these results suggest that TDP-43 is a conserved host target of HIV-1 Vpu and provide evidence for the involvement of TDP-43 dysregulation in the neural pathogenesis of HIV-1.

Indexed as

Caspase 3DNA-Binding ProteinsHIV-1Human Immunodeficiency Virus ProteinsProteolysisViral Regulatory and Accessory ProteinsHEK293 CellsHIV InfectionsHumansNeuronsViroporin ProteinsCASP3 protein, humanCaspase 3DNA-Binding ProteinsHuman Immunodeficiency Virus ProteinsTARDBP protein, humanViral Regulatory and Accessory ProteinsViroporin Proteinsvpu protein, Human immunodeficiency virus 1Caspase 3HIV-1NeurotoxicityTDP-43Vpu

Identifiers

PMID39242776
PMCPMC11467202

What Socratic holds

Textmetadata
LicenceCC BY
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.