Evidence map›Paper›PMID 41481472›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

L-lactic acid enhances type I interferon immune response and inhibits virus infection by promoting IRF9 L-lactylation.

Ying Miao, Qun Cui, Tingting Zhang, Renxia Zhang, Qian Zhao, Haiyan Zhou, Yibo Zuo, Qin Wang, Yuerong Zhang, Zhijin Zheng and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. 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. Review
  2. Article
  3. Review
  4. 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

14 authors.

Ying MiaoDepartment of Laboratory Medicine, Institute of Laboratory Medicine, Translational Clinical Immunology Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, China.
Qun CuiInstitutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu 215123, China.
Tingting ZhangDepartment of Laboratory Medicine, Institute of Laboratory Medicine, Translational Clinical Immunology Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, China.
Renxia ZhangInstitutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu 215123, China.
Qian ZhaoInstitutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu 215123, China.
Haiyan ZhouDepartment of Laboratory Medicine, Institute of Laboratory Medicine, Translational Clinical Immunology Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, China.
Yibo ZuoDepartment of Laboratory Medicine, Institute of Laboratory Medicine, Translational Clinical Immunology Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, China.
Qin WangDepartment of Laboratory Medicine, Institute of Laboratory Medicine, Translational Clinical Immunology Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, China.
Yuerong ZhangDepartment of Laboratory Medicine, Institute of Laboratory Medicine, Translational Clinical Immunology Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, China.
Zhijin ZhengInstitutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu 215123, China.
Wei HeInstitutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu 215123, China.
Chunyan LiuDepartment of Laboratory Medicine, Institute of Laboratory Medicine, Translational Clinical Immunology Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, China.
Yukang YuanDepartment of Laboratory Medicine, Institute of Laboratory Medicine, Translational Clinical Immunology Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, China.ORCID 0000-0003-3153-2408
Hui ZhengDepartment of Laboratory Medicine, Institute of Laboratory Medicine, Translational Clinical Immunology Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, China.ORCID 0000-0002-4325-4946

Funding

China Postdoctoral Science Foundation () 2024M750364MOST | National Natural Science Foundation of China (NSFC) 32241009 82572022 82502139 82571033National Key R&D Program of China 2023YFA1800200Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) PAPDSichuan Science and Technology Program 2025ZNSFSC1095
6 · The paper itself

Abstract

Lysine lactylation is a crucial posttranslational modification (PTM) that regulates protein function. Here, this study revealed that L-lactic acid promotes host immune response and inhibits viral infection by inducing Interferon Regulatory Factor 9 (IRF9) L-lactylation. We first found L-lactylation modification (L-Kla) of IRF9 mediated by AARS1. Further studies demonstrated that IRF9 L-lactylation potentiates type I interferon (IFN-I) signaling by promoting IRF9-STAT2 interaction, thereby boosting antiviral immune response. Intriguingly, L-lactic acid exhibits dual effects on viral infection: L-lactic acid exhibits antiviral effects at physiological and moderately elevated levels but proviral effects at high levels. Furthermore, we found that the viruses can achieve immune evasion by promoting SIRT1-mediated delactylation of IRF9. Interestingly, we uncovered that metformin promotes IRF9 L-lactylation by both accumulating lactic acid and disrupting virus-induced IRF9-SIRT1 interaction. These findings renew the understanding of the roles of lactic acid in antiviral immune response and determine metformin's immunomodulatory effects on antiviral immunity through regulating IRF9 L-lactylation.

Indexed as

Interferon-Stimulated Gene Factor 3, gamma SubunitInterferon Type ILactic AcidVirus DiseasesAnimalsAntiviral AgentsHEK293 CellsHumansMetforminMiceProtein Processing, Post-TranslationalSignal TransductionSirtuin 1STAT2 Transcription FactorAntiviral AgentsInterferon-Stimulated Gene Factor 3, gamma SubunitInterferon Type IIRF9 protein, humanLactic AcidMetforminSIRT1 protein, humanSirtuin 1STAT2 protein, humanSTAT2 Transcription Factorantiviral immunityIRF9L-lactic acidlysine lactylationmetformin

Identifiers

PMID41481472
PMCPMC12773741

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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.