O -GlcNAc transferase promotes influenza A virus-induced cytokine storm by targeting interferon regulatory factor-5
In this study, we demonstrated an essential function of the hexosamine biosynthesis pathway (HBP)-associated -linked β- -acetylglucosamine ( -GlcNAc) signaling in influenza A virus (IAV)-induced cytokine storm. -GlcNAc transferase (OGT), a key enzyme for protein -GlcNAcylation, mediated IAV-induced...
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Published in | Science advances Vol. 6; no. 16; p. eaaz7086 |
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Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Association for the Advancement of Science
01.04.2020
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Subjects | |
Online Access | Get full text |
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Summary: | In this study, we demonstrated an essential function of the hexosamine biosynthesis pathway (HBP)-associated
-linked β-
-acetylglucosamine (
-GlcNAc) signaling in influenza A virus (IAV)-induced cytokine storm.
-GlcNAc transferase (OGT), a key enzyme for protein
-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
-GlcNAcylation of IRF5 on serine-430.
-GlcNAcylation of IRF5 is required for K63-linked ubiquitination of IRF5 and subsequent cytokine production. Analysis of clinical samples revealed that IRF5 is
-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
-GlcNAcylation regulates IRF5 function during IAV infection, highlighting the importance of glucose metabolism in IAV-induced cytokine storm. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2375-2548 2375-2548 |
DOI: | 10.1126/sciadv.aaz7086 |