1. O -GlcNAc transferase promotes influenza A virus–induced cytokine storm by targeting interferon regulatory factor–5
- Author
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Mengqi Li, Fubing Wang, Aidong Chen, Shi Liu, Yu Yi, Qiming Wang, Yong Lin, Guoping Peng, Nanfang Peng, Ying Zhu, Yuan Rong, Zhang Yi, Haisheng Yu, Peining Fang, Li-qun Rao, Rui He, Mengji Lu, and Li Zhou
- Subjects
medicine.medical_treatment ,Medizin ,medicine.disease_cause ,Proinflammatory cytokine ,03 medical and health sciences ,0302 clinical medicine ,Ubiquitin ,Interferon ,Virology ,medicine ,Influenza A virus ,Research Articles ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,biology ,SciAdv r-articles ,medicine.disease ,Cell biology ,Cytokine ,biology.protein ,Cytokine storm ,030217 neurology & neurosurgery ,IRF5 ,Research Article ,Signal Transduction ,Interferon regulatory factors ,medicine.drug - Abstract
IAV regulates inflammatory signaling via glucose metabolism., In this study, we demonstrated an essential function of the hexosamine biosynthesis pathway (HBP)–associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in influenza A virus (IAV)–induced cytokine storm. O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, mediated IAV-induced cytokine production. Upon investigating the mechanisms driving this event, we determined that IAV induced OGT to bind to interferon regulatory factor–5 (IRF5), leading to O-GlcNAcylation of IRF5 on serine-430. O-GlcNAcylation of IRF5 is required for K63-linked ubiquitination of IRF5 and subsequent cytokine production. Analysis of clinical samples revealed that IRF5 is O-GlcNAcylated, and higher levels of proinflammatory cytokines correlated with higher levels of blood glucose in IAV-infected patients. We identified a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates IRF5 function during IAV infection, highlighting the importance of glucose metabolism in IAV-induced cytokine storm.
- Published
- 2020