O-GlcNAc transferase plays dual antiviral roles by integrating innate immunity and lipid metabolism

Hong Dong, Chenxi Liang, Junjie Zhang, Weidong Wu, Nitesh Kumar, Zihao Liu, Yajun Sun, Zhiwei Liao, Xiaolin Cheng, Yanbao Yu, Yong Zhang, Michael J. Holtzman, Jianrong Li, Kymberly M. Gowdy, Paul G. Thomas, Jovica D. Badjic, Anjun Ma, Qin Ma, Jacob S. Yount, Shan-Lu Liu and Haitao Wen ()
Additional contact information
Hong Dong: The Ohio State University
Chenxi Liang: The Ohio State University
Junjie Zhang: The Ohio State University
Weidong Wu: The Ohio State University
Nitesh Kumar: The Ohio State University
Zihao Liu: The Ohio State University
Yajun Sun: The Ohio State University
Zhiwei Liao: The Ohio State University
Xiaolin Cheng: The Ohio State University
Yanbao Yu: University of Delaware
Yong Zhang: Washington University School of Medicine
Michael J. Holtzman: Washington University School of Medicine
Jianrong Li: The Ohio State University
Kymberly M. Gowdy: The Ohio State University
Paul G. Thomas: St. Jude Children’s Research Hospital
Jovica D. Badjic: The Ohio State University
Anjun Ma: The Ohio State University
Qin Ma: The Ohio State University
Jacob S. Yount: The Ohio State University
Shan-Lu Liu: The Ohio State University
Haitao Wen: The Ohio State University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Viral infection induces robust reprogramming of metabolic pathways in host cells. However, whether host metabolic enzymes detect viral components remains unknown. Our group and others previously identified O-GlcNAc transferase (OGT), an important glucose metabolic enzyme, as a crucial mediator of the antiviral immune responses. Here, by studying a mouse model with a catalytically impaired OGT, we discover a catalytic activity-independent function of OGT in restraining influenza A virus (IAV) infection in addition to its catalytic activity-dependent effect on MAVS-mediated antiviral immunity. Biochemical studies reveal a critical antiviral effect based on OGT interacting with IAV genomic RNA that requires its N-terminal tetracopeptide repeat-4 motif. This interaction causes the translocation of nuclear OGT to cytosolic lipid droplets (LDs) to destabilize LDs-coating perilipin 2, thereby limiting LDs accumulation and in turn virus replication. In sum, our findings reveal OGT as a multifaceted metabolic sensor that integrates MAVS signaling and lipid metabolism to combat viral infection.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-63085-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63085-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-63085-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().