2. Academic Validation
  3. Oxaloacetate sensing promotes innate immune antiviral defence against influenza virus infection

Oxaloacetate sensing promotes innate immune antiviral defence against influenza virus infection

  • Nat Microbiol. 2025 Oct;10(10):2521-2536. doi: 10.1038/s41564-025-02107-3.
Shouheng Jin # 1,  Xing He # 1,  Zheyu Wang 1,  Tao Zhou 1,  Jun Wang 2 3,  Guihong Pan 3,  Yin Zhang 1,  Ling Ma 1,  Shuai Yang 1,  Liqiu Wang 1,  Yaoxing Wu 1 4,  Yilin Zou 1 5,  Nan Qi 5,  Jun Cui 6
Affiliations

Affiliations

  • 1 Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • 2 Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • 4 Department of Critical Care Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 5 Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou, China.
  • 6 Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China. cuij5@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 40983701 DOI: 10.1038/s41564-025-02107-3
Abstract

Metabolic pathways determine cellular fate and function; however, the exact roles of metabolites in host defence against Influenza Virus remain undefined. Here we employed pharmacological inhibition and metabolomics analysis to show that the metabolic pathways of oxaloacetate (OAA) are integrated with Antiviral responses to Influenza Virus. Cytosolic malate dehydrogenase 1 senses intracellular OAA to undergo dimerization and functions as a scaffold to recruit the transcription factor ETS2 for phosphorylation by the kinase TAOK1 at serine 313. The phosphorylated ETS2 translocates into the nucleus and supports optimal expression of TBK1, an indispensable activator of type I interferon responses. OAA supplementation provides a broad-spectrum Antiviral ability, and OAA deficiency caused by Acly genetic ablation decreases Antiviral immunity and renders mice more susceptible to lethal H1N1 virus Infection. Our results uncover a signalling pathway through cellular OAA sensing that links metabolism and innate immunity to coordinate defence against viral challenge.

Figures
Products