Innate immunity
How interferon throttles sterol synthesis in antiviral defense
Open access · cc by · source: Europe PMC
Type I interferon couples viral sensing to down-regulation of the sterol pathway’s mevalonate–isoprenoid arm, limiting viral growth.
Study at a glance
- Design
- Animal / in-vitro — Macrophage time-series, lipidomics, IFN receptor knockouts, and murine CMV infection models
- N
- Multi-assay mouse/cell study — no single primary analytic N in stored text
- Population
- Primary bone-marrow–derived macrophages and mice (including IFNAR1/Tyk2 models)
- Outcome
- Interferon-mediated sterol-pathway down-regulation in antiviral defense
Structured fields used in claim comparison tables when every cited study has a complete layer.
Key findings
Infection and type I/II IFN coordinately reduce sterol-pathway transcripts and metabolites via IFNAR1/Tyk2 signaling and lowered SREBP2. Antiviral effects of pathway blockade depend on mevalonate/geranylgeraniol, not cholesterol rescue.
Methodology
Authors combined macrophage time-series expression, lipidomics, IFN receptor knockouts, statin/siRNA perturbations, and in vivo murine CMV infection to test whether interferon regulates sterol metabolism for antiviral defense.
Limitations
This is murine CMV/macrophage mechanism work, not a human statin antiviral trial; branch-point enzymology still needs finer mapping.
How this study connects
Role on claims
Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.
Multiple empirical papers in this library examine innate immunity with mechanistic biological findings.
Evidence for the claim as stated.
Infection and type I/II IFN coordinately reduce sterol-pathway transcripts and metabolites via IFNAR1/Tyk2 signaling and lowered SREBP2. Antiviral effects of pathway blockade depend on mevalonate/geranylgeraniol, not cholesterol rescue.
Evidence for the claim as stated.
Systems and scales differ across innate immunity studies (species, tissues, methods), so mechanisms should not be over-generalised.
Evidence for the claim as stated.
Interferon programs reshape host gene expression during viral defense.
Host-defense work shows interferon-mediated down-regulation as part of antiviral control—effector-layer evidence beside sensor identity.
Evidence for the claim as stated.
Which sensor fires in one epithelial infection model does not settle interferon effector strategies across all viruses or tissues.
Evidence for the claim as stated.
Interferon receptor knockouts plus statin/siRNA perturbations tied antiviral defense to sterol-pathway shutdown. Infection and type I/II IFN reduced sterol-pathway transcripts and metabolites via IFNAR1/Tyk2 and lowered SREBP2; antiviral effects of pathway blockade depended on mevalonate/geranylgeraniol, not cholesterol rescue. This is murine CMV/macrophage mechanism work, not a human statin antiviral trial.
Evidence for the claim as stated.
Loss-of-function tools are not interchangeable. CK1ε used shRNA plus inhibitors in mammalian cancer models; USP8 used Drosophila RNAi; IFN work used receptor knockouts and siRNA in macrophages; PDLP used plant combined KOs. A 'knockdown paper' in flies is not the same genetic lesion as a mouse IFNAR1 knockout or an Arabidopsis double mutant.
Evidence for the claim as stated.
Open questions
Tensions this paper is part of
From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.
Systems and scales differ across innate immunity studies (species, tissues, methods), so mechanisms should not be over-generalised.
Which sensor fires in one epithelial infection model does not settle interferon effector strategies across all viruses or tissues.
Loss-of-function tools are not interchangeable. CK1ε used shRNA plus inhibitors in mammalian cancer models; USP8 used Drosophila RNAi; IFN work used receptor knockouts and siRNA in macrophages; PDLP used plant combined KOs. A 'knockdown paper' in flies is not the same genetic lesion as a mouse IFNAR1 knockout or an Arabidopsis double mutant.
- Supports · CK1ε, PERIOD2, and cancer-selective growth arrest
- Supports · How does USP8 turn on Smoothened?
- Supports · How do proteins find plasmodesmata?
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Same topic cluster — not a recommendation engine.