ArticleNature immunology2022
Deactylation by SIRT1 enables liquid-liquid phase separation of IRF3/IRF7 in innate antiviral immunity.
Article in Nature immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Liquid-liquid phase separation drives immune signaling transduction in cancer: a bibliometric and visualized study from 1992 to 2024.Frontiers in oncology · 2025Pooled it
- Remodeling of innate antiviral immunity in aging.Cell insight · 2026Review
- SIRT1 Inhibits T-cell Infiltration and Tertiary Lymphoid Structure Formation to Promote Radioimmunotherapy Resistance.Cancer research · 2026Article
- SIRT1 remodels astrocyte metabolism and promotes viral replication during neurotropic orthoflavivirus infection.bioRxiv : the preprint server for biology · 2026Article
- IFI208, an interferon-stimulated gene, promotes host antiviral responses through liquid-liquid phase separation of MDA5.Nature communications · 2026Article
- Multifaceted effects of proline on intestinal injury, inflammation, and lipid metabolism in piglets induced by porcine epidemic diarrhea virus.Amino acids · 2026Article
- A targetable micropeptide reprograms macrophages to suppress T cell anti-tumor immunity.Nature cancer · 2026Article
- Dysregulation of liquid-liquid phase separation: from molecular mechanisms to targeted therapies in cardiovascular diseases.Journal of nanobiotechnology · 2026Review
- A novel microprotein L3EMP triggers lung adenocarcinoma progression by catalysing the deubiquitination of SIRT1.British journal of cancer · 2026Article
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- Lactylation and acetylation: parallel paths, divergent deeds, and research dilemmas.Journal of translational medicine · 2026Review
- Occludin modulates HIV and ischaemic stroke response via the mitochondrial antiviral signalling pathway.Brain : a journal of neurology · 2026Article
- SIRT4 regulates antiviral and autoimmune responses by promoting cGAS-mediated signaling pathways.EMBO reports · 2026Article
- The cGAS-STING pathway at the crossroads of neuroimmunology: bridging innate immunity to aging and neurodegeneration.Biomarker research · 2026Review
- Phase separation and the tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Targeting DAP5 Disrupts Alternate Mode of Translational Initiation in Tregs and Potentiates Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- HRS Degradation-Induced Nicotinamide Deficiency in Placental Extracellular Vesicles Triggers Preeclampsia by Disrupting Maternal-Fetal Immune Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SVCV phosphoprotein hijacks phase separation to immobilize the IRF3-TBK1 signaling axis and suppress interferon antiviral immunity.Journal of virology · 2026Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Innate antiviral immunity deteriorates with aging but how this occurs is not entirely clear. Here we identified SIRT1-mediated DNA-binding domain (DBD) deacetylation as a critical step for IRF3/7 activation that is inhibited during aging. Viral-stimulated IRF3 underwent liquid-liquid phase separation (LLPS) with interferon (IFN)-stimulated response element DNA and compartmentalized IRF7 in the nucleus, thereby stimulating type I IFN (IFN-I) expression. SIRT1 deficiency resulted in IRF3/IRF7 hyperacetylation in the DBD, which inhibited LLPS and innate immunity, resulting in increased viral load and mortality in mice. By developing a genetic code expansion orthogonal system, we demonstrated the presence of an acetyl moiety at specific IRF3/IRF7 DBD site/s abolish IRF3/IRF7 LLPS and IFN-I induction. SIRT1 agonists rescued SIRT1 activity in aged mice, restored IFN signaling and thus antagonized viral replication. These findings not only identify a mechanism by which SIRT1 regulates IFN production by affecting IRF3/IRF7 LLPS, but also provide information on the drivers of innate immunosenescence.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.