Evidence map›Paper›PMID 39730330›Full record

ArticleSignal transduction and targeted therapy2024

Itaconate facilitates viral infection via alkylating GDI2 and retaining Rab GTPase on the membrane.

Shulei Yin, Yijie Tao, Tianliang Li, Chunzhen Li, Yani Cui, Yunyan Zhang, Shenhui Yin, Liyuan Zhao, Panpan Hu, Likun Cui and 12 more

Abstract read
In one paragraph

Article in Signal transduction and targeted therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Review
  2. Review
  3. Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026
    Review
  4. Article
  5. Ketamine and Evolving Neuroplasticity.Clinical drug investigation · 2026
    Review
  6. Review
  7. NKRInflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
  8. Understanding the Therapeutic Potential of PD-1 Agonism in Inflammatory and Autoimmune Disorders.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  9. Rab27: Molecular switch of tumor exosome secretion (Review).International journal of molecular medicine · 2026
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Itaconate modifications: Mechanisms and applications.Journal of intensive medicine · 2026
    Review
  15. Article
  16. GDI2 protein: research progress and its mechanisms in diseases.Frontiers in cell and developmental biology · 2026
    Review
  17. Article
  18. 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

22 authors.

Shulei Yin *National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Yijie Tao *School of Anesthesiology, Naval Medical University, Shanghai, 200433, China.
Tianliang Li *National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Chunzhen Li *National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Yani CuiSchool of Anesthesiology, Naval Medical University, Shanghai, 200433, China.
Yunyan ZhangDepartment of Respiratory and Critical Care Medicine, Changzheng Hospital, Naval Medical University, Shanghai, 200433, China.
Shenhui YinNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Liyuan ZhaoNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Panpan HuSchool of Anesthesiology, Naval Medical University, Shanghai, 200433, China.
Likun CuiNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Yunyang WuDepartment of Traditional Chinese Medicine, Naval Medical University, Shanghai, 200433, China.
Yixian HeNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Shu YuNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Jie ChenNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Shaoteng LuNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Guifang QiuNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Mengqi SongNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Qianshan HouNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Cheng QianNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Zui ZouNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China. zouzui@smmu.edu.cn.
Sheng XuNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China. xusheng@immunol.org.
Yizhi YuNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China. yuyz@immunol.org.ORCID 0000-0002-3793-1154

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81670072National Natural Science Foundation of China (National Science Foundation of China) 81871253National Natural Science Foundation of China (National Science Foundation of China) 82071789National Natural Science Foundation of China (National Science Foundation of China) 82101854National Natural Science Foundation of China (National Science Foundation of China) 82371749National Natural Science Foundation of China (National Science Foundation of China) 82371782
6 · The paper itself

Abstract

Metabolic reprogramming of host cells plays critical roles during viral infection. Itaconate, a metabolite produced from cis-aconitate in the tricarboxylic acid cycle (TCA) by immune responsive gene 1 (IRG1), is involved in regulating innate immune response and pathogen infection. However, its involvement in viral infection and underlying mechanisms remain incompletely understood. Here, we demonstrate that the IRG1-itaconate axis facilitates the infections of VSV and IAV in macrophages and epithelial cells via Rab GTPases redistribution. Mechanistically, itaconate promotes the retention of Rab GTPases on the membrane via directly alkylating Rab GDP dissociation inhibitor beta (GDI2), the latter of which extracts Rab GTPases from the membrane to the cytoplasm. Multiple alkylated residues by itaconate, including cysteines 203, 335, and 414 on GDI2, were found to be important during viral infection. Additionally, this effect of itaconate needs an adequate distribution of Rab GTPases on the membrane, which relies on Rab geranylgeranyl transferase (GGTase-II)-mediated geranylgeranylation of Rab GTPases. The single-cell RNA sequencing data revealed high expression of IRG1 primarily in neutrophils during viral infection. Co-cultured and in vivo animal experiments demonstrated that itaconate produced by neutrophils plays a dominant role in promoting viral infection. Overall, our study reveals that neutrophils-derived itaconate facilitates viral infection via redistribution of Rab GTPases, suggesting potential targets for antiviral therapy.

Indexed as

rab GTP-Binding ProteinsSuccinatesAnimalsCell MembraneGuanine Nucleotide Dissociation InhibitorsHumansHydro-LyasesMacrophagesMiceVirus DiseasesAcod1 protein, mouseGuanine Nucleotide Dissociation InhibitorsHydro-Lyasesitaconic acidrab GTP-Binding ProteinsSuccinates

Identifiers

PMID39730330
PMCPMC11681089

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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 OpenQuestion graph.