Evidence map›Paper›PMID 39719712›Full record

ArticleImmunity2025

Pyrimidine synthesis enzyme CTP synthetase 1 suppresses antiviral interferon induction by deamidating IRF3.

Youliang Rao, Chao Qin, Ali Can Savas, Qizhi Liu, Shu Feng, Guoli Hou, Taolin Xie, Pinghui Feng

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2025. 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. Article
  2. Article
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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.

Youliang RaoSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.
Chao QinSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.
Ali Can SavasSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.
Qizhi LiuSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.
Shu FengSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.
Guoli HouSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.
Taolin XieSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.
Pinghui FengSection of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: pinghuif@usc.edu.

Funding

Explore roles of HSV-1 in Alzheimer's disease using mouse modelsR01AG070904 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHEN, CASEY, FENG, PINGHUI · 2021 to 2025
$3.9M
Targeting IKKepsilon-mediated nucleotide synthesis in KSHV-associated lymphomaR01CA285192 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Pinghui Feng · 2023 to 2026
$1.5M
Targeting the UL37 deamidase to impede HSV-1 infection.R21AI180537 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI FENG, PINGHUI · 2024 to 2025
$450k
NCI NIH HHS R01 CA285192NIAID NIH HHS R21 AI180537NIA NIH HHS R01 AG070904
6 · The paper itself

Abstract

Metabolism is typically contextualized in conjunction with proliferation and growth. The roles of metabolic enzymes beyond metabolism-such as in innate immune responses-are underexplored. Using a focused short hairpin RNA (shRNA)-mediated screen, we identified CTP synthetase 1 (CTPS1), a rate-limiting enzyme of pyrimidine synthesis, as a negative regulator of interferon induction. Mechanistically, CTPS1 interacts with and deamidates interferon regulatory factor 3 (IRF3). Deamidation at N85 impairs IRF3 binding to promoters containing IRF3-responsive elements, thus muting interferon (IFN) induction. Employing CTPS1 conditional deletion and IRF3 deamidated or deamidation-resistant knockin mice, we demonstrated that CTPS1-driven IRF3 deamidation restricts IFN induction in response to viral infection in vivo. However, during immune activation, IRF3 deamidation by CTPS1 is inhibited by glycogen synthase kinase 3 beta (GSK3β) to promote IFN induction. This work demonstrates how CTPS1 tames innate immunity independent of its role in pyrimidine synthesis, thus expanding the functional repertoire of metabolic enzymes into immune regulation.

Indexed as

Carbon-Nitrogen LigasesInterferon Regulatory Factor-3InterferonsPyrimidinesAnimalsGlycogen Synthase Kinase 3 betaHEK293 CellsHumansImmunity, InnateMiceMice, Inbred C57BLMice, KnockoutCarbon-Nitrogen LigasesCTP synthetaseGlycogen Synthase Kinase 3 betaInterferon Regulatory Factor-3InterferonsIrf3 protein, mousepyrimidinePyrimidinesCTP synthetaseinterferon productioninterferon regulatory factorprotein deamidationpyrimidine synthesis enzymeRNA and DNA viruses

Identifiers

PMID39719712
PMCPMC11735333

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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.