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O-GlcNAc transferase senses influenza viral RNA and restricts viral infection by integrating innate immunity and lipid metabolism

GSE297354 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2025/07/15 Platform GPL34284
Summary
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, we discover an enzyme-independent function of OGT in restraining influenza A virus (IAV) infection in addition to its enzyme-dependent effect on MAVS-mediated antiviral immunity by studying a mouse model with an enzyme-inactive OGT. Biochemical studies reveal a critical antiviral effect based on OGT N-terminal tetracopeptide repeat-4-domain binding to IAV genomic RNA. This binding 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.
Published in
O-GlcNAc transferase plays dual antiviral roles by integrating innate immunity and lipid metabolism
Dong H, Liang C, Zhang J et al. · Nature communications 2025 · PMID 40830102 · doi:10.1038/s41467-025-63085-y
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Direct links to NCBI, no account and no request form: the whole study as GSE297354_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 8 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1263611 and SRA study SRP585735. Searching any of these in the dataset finder brings you back here.

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