O-GlcNAc transferase senses influenza viral RNA and restricts viral infection by integrating innate immunity and lipid metabolism
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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, 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.
ORGANISM(S): Homo sapiens
PROVIDER: GSE297354 | GEO | 2025/07/15
REPOSITORIES: GEO
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