Evidence mapPaperPMID 39563434Full record

ArticleStem cell research & therapy2024

miRNA-431-5p enriched in EVs derived from IFN-β stimulated MSCs potently inhibited ZIKV through CD95 downregulation.

Meng Yuan, Xiaoyan Tian, Wenyuan Ma, Rui Zhang, Xue Zou, Yu Jin, Nan Zheng, Zhiwei Wu, Yongxiang Wang

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Virus infection and vesicle trafficking.Frontiers in immunology · 2025
    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

9 authors.

Meng YuanCenter for Public Health Research, Medical School, Nanjing University, Nanjing, 210093, China.
Xiaoyan TianCenter for Public Health Research, Medical School, Nanjing University, Nanjing, 210093, China.
Wenyuan MaCenter for Public Health Research, Medical School, Nanjing University, Nanjing, 210093, China.
Rui ZhangDepartment of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, PR China.
Xue ZouCenter for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, 43205, USA.
Yu JinDepartment of Clinical Medicine, Medical School of Nanjing University , Nanjing, 210093, China. jinyu@nju.edu.cn.
Nan ZhengCenter for Public Health Research, Medical School, Nanjing University, Nanjing, 210093, China. nanzheng@nju.edu.cn.
Zhiwei WuCenter for Public Health Research, Medical School, Nanjing University, Nanjing, 210093, China. wzhw@nju.edu.cn.ORCID 0000-0002-0672-948X
Yongxiang WangDepartment of Orthopedics, Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School,Nanjing University, Yangzhou, China. wangyongxiang@nju.edu.cn.

Funding

National Natural Science Foundation of China 31970149National Natural Science Foundation of China 81672020National Natural Science Foundation of China 82072423National Natural Science Foundation of China 82272502National Natural Science Foundation of China U22A20335Nation Key Research and Development Program of China 2023YFB3810200Nation Key Research and Development Program of China 2023YFB3810204
6 · The paper itself

Abstract

backgroundZika virus (ZIKV) primarily spreads through mosquito bites and can lead to microcephaly in infants and Guillain-Barre syndrome in adults. It is noteworthy that ZIKV can persist in the semen of infected males for extended periods and can be sexually transmitted. Infection with ZIKV has severe pathological manifestations on the testicular tissues of male mice, resulting in reduced sperm motility and fertility. However, there are no approved prophylactic vaccines or therapeutics available to treat Zika virus infection.

methodsUsing a male type I and II interferon receptor-deficient (ifnar1(-/-) ifngr1(-/-)) C57BL/6 (AG6) mouse model infected with ZIKV as a representative model, we evaluated the degree of testicular damage and viral replication in various organs in mice treated with EVs derived from MSC-stimulated with IFN-β (IFNβ-EVs) and treated with controls. We measured testicle size, detected viral load in various organs, and analyzed gene expression to assess treatment efficacy.

resultsOur findings demonstrated that intravenous administration of IFNβ-EVs effectively suppressed ZIKV replication in the testes. Investigation with in-depth RNA sequencing analysis found that IFN-β treatment changed the cargo miRNA of EVs. Notably, miR-431-5p was identified to be significantly enriched in IFNβ-EVs and exhibited potent antiviral activity in vitro. We showed that CD95 was a direct downstream target for miR-431-5p and played a role in facilitating ZIKV replication. miR-431-5p effectively downregulated the expression of CD95 protein, consequently promoted the phosphorylation and nuclear localization of NF-kB, which resulted in the activation of anti-viral status, leading to the suppression of viral replication.

conclusionsOur study demonstrated that the EVs produced by IFNβ-treated MSCs could effectively convey antiviral activity.

Indexed as

Interferon-betaMesenchymal Stem CellsMice, Inbred C57BLMicroRNAsZika VirusZika Virus InfectionAnimalsDown-Regulationfas ReceptorHumansMaleMiceReceptor, Interferon alpha-betaTestisVirus Replicationfas ReceptorInterferon-betaMicroRNAsReceptor, Interferon alpha-betaCD95Extracellular vesicles (EVs)IFN-βmiR-431-5pMSCsZika virus (ZIKV)

Identifiers

PMID39563434
PMCPMC11575116

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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 Socratic graph.