O-GlcNAc transferase promotes influenza A virus-induced cytokine storm by targeting interferon regulatory factor-5

被引：97

作者：

Wang, Qiming ^{[1
]}

Fang, Peining ^{[2
]}

He, Rui ^{[2
]}

Li, Mengqi ^{[2
]}

Yu, Haisheng ^{[2
]}

Zhou, Li ^{[2
]}

Yi, Yu ^{[3
]}

Wang, Fubing ^{[4
]}

Rong, Yuan ^{[4
]}

Zhang, Yi ^{[5
]}

Chen, Aidong ^{[6
]}

Peng, Nanfang ^{[2
]}

Linz, Yong ^{[7
]}

Lu, Mengji ^{[8
]}

Zhu, Ying ^{[2
]}

Peng, Guoping ^{[1
,9
]}

Rao, Liqun ^{[1
,9
]}

Liu, Shi ^{[2
]}

机构：

[1] Human Agr Univ, Coll Biosci & Biotechnol, Changsha 410128, Human Province, Peoples R China

[2] Wuhan Univ, Coll Life Sci, Modern Virol Res Ctr, State Key Lab Virol, Wuhan 430072, Peoples R China

[3] Zhejiang Univ, Minist Educ & Innovat, Ctr Cell Signaling Network, Life Sci Inst,Key Lab Biosyst Homeostasis & Prote, Hangzhou, Zhejiang, Peoples R China

[4] Wuhan Univ, Zhongnan Hosp, Dept Lab Med, Wuhan, Peoples R China

[5] Hubei Univ Technol, Coll Food & Pharmaceut Engn, Hubei Prov Cooperat Innovat Ctr Ind Fermentat, Wuhan 430068, Peoples R China

[6] Nanjing Med Univ, Dept Physiol, Nanjing 211166, Peoples R China

[7] Chongqing Med Univ, Chinese Minist Educ, Key Lab Mol Biol Infect Dis Designated, Yixueyuan Rd, Chongqing, Peoples R China

[8] Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, D-45122 Essen, Germany

[9] Human Engn Lab Good Agr Practice & Comprehens Uti, Changsha 410128, Peoples R China

来源：

SCIENCE ADVANCES | 2020年 / 6卷 / 16期

基金：

中国国家自然科学基金;

关键词：

LINKS GLUCOSE-METABOLISM; N-ACETYLGLUCOSAMINE; GLCNACYLATION; PHOSPHORYLATION; TRANSCRIPTION; REPLICATION; EXPRESSION; ROLES; BETA; IRF5;

D O I：

10.1126/sciadv.aaz7086

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In this study, we demonstrated an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked beta-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.

引用

页数：13

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