tetano
Editor, Senior Moderator
Sci Adv
. 2020 Apr 15;6(16):eaaz7086.
doi: 10.1126/sciadv.aaz7086. eCollection 2020 Apr.
O-GlcNAc Transferase Promotes Influenza A Virus-Induced Cytokine Storm by Targeting Interferon Regulatory factor-5
Qiming Wang[SUP] 1 [/SUP], Peining Fang[SUP] 2 [/SUP], Rui He[SUP] 2 [/SUP], Mengqi Li[SUP] 2 [/SUP], Haisheng Yu[SUP] 2 [/SUP], Li Zhou[SUP] 2 [/SUP], Yu Yi[SUP] 3 [/SUP], Fubing Wang[SUP] 4 [/SUP], Yuan Rong[SUP] 4 [/SUP], Yi Zhang[SUP] 5 [/SUP], Aidong Chen[SUP] 6 [/SUP], Nanfang Peng[SUP] 2 [/SUP], Yong Lin[SUP] 7 [/SUP], Mengji Lu[SUP] 8 [/SUP], Ying Zhu[SUP] 2 [/SUP], Guoping Peng[SUP] 1 9 [/SUP], Liqun Rao[SUP] 1 9 [/SUP], Shi Liu[SUP] 2 [/SUP]
Affiliations
Abstract
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.
. 2020 Apr 15;6(16):eaaz7086.
doi: 10.1126/sciadv.aaz7086. eCollection 2020 Apr.
O-GlcNAc Transferase Promotes Influenza A Virus-Induced Cytokine Storm by Targeting Interferon Regulatory factor-5
Qiming Wang[SUP] 1 [/SUP], Peining Fang[SUP] 2 [/SUP], Rui He[SUP] 2 [/SUP], Mengqi Li[SUP] 2 [/SUP], Haisheng Yu[SUP] 2 [/SUP], Li Zhou[SUP] 2 [/SUP], Yu Yi[SUP] 3 [/SUP], Fubing Wang[SUP] 4 [/SUP], Yuan Rong[SUP] 4 [/SUP], Yi Zhang[SUP] 5 [/SUP], Aidong Chen[SUP] 6 [/SUP], Nanfang Peng[SUP] 2 [/SUP], Yong Lin[SUP] 7 [/SUP], Mengji Lu[SUP] 8 [/SUP], Ying Zhu[SUP] 2 [/SUP], Guoping Peng[SUP] 1 9 [/SUP], Liqun Rao[SUP] 1 9 [/SUP], Shi Liu[SUP] 2 [/SUP]
Affiliations
- PMID: 32494619
- PMCID: PMC7159909
- DOI: 10.1126/sciadv.aaz7086
Abstract
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.