Evidence map›Paper›PMID 38429625›Full record

ArticleCell communication and signaling : CCS2024

O-GlcNAc of STING mediates antiviral innate immunity.

Yujia Li, Wang An, Liyuan Lu, Jiali Yuan, Danhui Wu, Qi Yang, Jinrong Guo, Jingyu Yang, Mengjie Liu, Kaiyue He and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

12 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Distinct O-Linked Glycosylation Systems in Signaling and Immune Regulation.International journal of molecular sciences · 2026
    Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. The STING signaling pathways and bacterial infection.Apoptosis : an international journal on programmed cell death · 2025
    Review
  10. Article
  11. Review
  12. 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

12 authors at 1 institution in 1 country.

Yujia LiSchool of Life Sciences, Henan University, Kaifeng, 475004, Henan, China.
Wang AnSchool of Life Sciences, Henan University, Kaifeng, 475004, Henan, China.
Liyuan LuSchool of Life Sciences, Henan University, Kaifeng, 475004, Henan, China.
Jiali YuanSchool of Life Sciences, Henan University, Kaifeng, 475004, Henan, China.
Danhui WuSchool of Life Sciences, Henan University, Kaifeng, 475004, Henan, China.
Qi YangSchool of Life Sciences, Henan University, Kaifeng, 475004, Henan, China.
Jinrong GuoSchool of Life Sciences, Henan University, Kaifeng, 475004, Henan, China.
Jingyu YangSchool of Life Sciences, Henan University, Kaifeng, 475004, Henan, China.
Mengjie LiuSchool of Life Sciences, Henan University, Kaifeng, 475004, Henan, China.
Kaiyue HeSchool of Life Sciences, Henan University, Kaifeng, 475004, Henan, China.
Xinyuan LeiSchool of Life Sciences, Henan University, Kaifeng, 475004, Henan, China.
Zhi-Xiang XuSchool of Life Sciences, Henan University, Kaifeng, 475004, Henan, China. zhixiangxu08@gmail.com.
Henan University · CN

Funding

National Key Research and Development Program of China 2023YFE0109800National Natural Science Foundation of China 82020108024
6 · The paper itself

Abstract

backgroundO-GlcNAcylation modification affects multiple physiological and pathophysiolocal functions of cells. Altered O-GlcNAcylation was reported to participate in antivirus response. Stimulator of interferon genes (STING) is an adaptor mediating DNA virus-induced innate immune response. Whether STING is able to be modified by O-GlcNAcylation and how O-GlcNAcylation affects STING-mediated anti-DNA virus response remain unknown.

methodsMetabolomics analysis was used for detecting metabolic alterations in HSV-1 infection cells. Succinylated wheat germ agglutinin (sWGA), co-immunoprecipitation, and pull-down assay were employed for determining O-GlcNAcylation. Mutagenesis PCR was applied for the generation of STING mutants. WT and Sting1

resultsSTING was functionally activated by O-GlcNAcylation in host cells challenged with HSV-1. We demonstrated that this signaling event was initiated by virus infection-enhanced hexosamine biosynthesis pathway (HBP). HSV-1 (or viral DNA mimics) promotes glucose metabolism of host cells with a marked increase in HBP, which provides donor glucosamine for O-GlcNAcylation. STING was O-GlcNAcylated on threonine 229, which led to lysine 63-linked ubiquitination of STING and activation of antiviral immune responses. Mutation of STING T229 to alanine abrogated STING activation and reduced HSV-1 stimulated production of interferon (IFN). Application of 6-diazo-5-oxonorleucine (DON), an agent that blocks the production of UDP-GlcNAc and inhibits O-GlcNAcylation, markedly attenuated the removal of HSV-1 in wild type C57BL/6 mice, leading to an increased viral retention, elevated infiltration of inflammatory cells, and worsened tissue damages to those displayed in STING gene knockout mice. Together, our data suggest that STING is O-GlcNAcylated in HSV-1, which is crucial for an effective antiviral innate immune response.

conclusionHSV-1 infection activates the generation of UDP-Glc-NAc by upregulating the HBP metabolism. Elevated UDP-Glc-NAc promotes the O-GlcNAcylation of STING, which mediates the anti-viral function of STING. Targeting O-GlcNAcylation of STING could be a useful strategy for antiviral innate immunity.

Indexed as

Herpesvirus 1, HumanMembrane ProteinsAnimalsImmunity, InnateInterferonsMiceMice, Inbred C57BLSTING ProteinUridine DiphosphateInterferonsMembrane ProteinsSting1 protein, mouseSTING ProteinUridine DiphosphateAntiviral innate immunityHBPHSV-1O-GlcNAcylationSTING

Identifiers

PMID38429625
PMCPMC10908090
OpenAlexW4392387014

What OpenQuestion 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 OpenQuestion graph.