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Comparison of gene expression in HeLa cells after treatment with IFN-b, IFN-g, or VPgEMCV.

GSE286568 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2025/10/31 Platform GPL34284
Summary
We uncovered that cells infected with the encephalomyocarditis virus (EMCV) release soluble factors that induce apoptosis in uninfected cells. These factors were identified as the cytokine TNF-α and the viral protein VPgEMCV, which is necessary for viral RNA synthesis. Intriguingly, we discovered that VPgEMCV also acts as a functional mimic of IFN-γ, activating its canonical signaling pathway. This includes phosphorylation of STAT1 and the induction of IRF-1 and iNOS, leading to increased nitric oxide (NO) production. The synergy of NO accumulation and TNF-α signaling initiates powerful apoptosis. To compare gene sets regulated by IFN-I signaling (IFN-b), IFN-II signaling (IFN-g), and VPgEMCV signaling, we utilized RNA-seq analysis. From the deep sequencing data, we further discovered that VPgEMCV induces a gene expression profile similar to IFN-II signaling (IFN-γ), while also uniquely downregulating a distinct subset of genes. Our findings reveal that this cytokine-mimicry function of VPgEMCV regulates genes to control both viral replication and disease pathogenesis.
Published in
A 20-amino-acid Cardiovirus protein exhibits cytokine-mimicry activity to regulate viral replication
Shirasaka Y, Takeuchi F, Koike S et al. · Cell reports 2026 · PMID 41405988 · doi:10.1016/j.celrep.2025.116740
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Also filed as BioProject PRJNA1209929 and SRA study SRP557006. Searching any of these in the dataset finder brings you back here.

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