ArticlePLoS pathogens2017
ISG15 governs mitochondrial function in macrophages following vaccinia virus infection.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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77 citing papers in PubMed, 105 citations in OpenAlex.
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- Dual human lung models reveal compartment-specific activity of anti-tuberculosis drugs and host-directed therapies.Microbiology spectrum · 2026Article
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- ADAR1 regulates dsRNA formation in nuclear and mitochondrial transcripts through editing-dependent and -independent mechanisms.Cell reports · 2026Article
- Proteomics and tracer metabolomics link GAPDH ISGylation to glycolytic control.Genome biology · 2026Article
- A type I interferon-mitochondrial axis regulates efferocytosis and interferon-stimulated gene induction in macrophages.Immunity · 2026Article
- IL-33-Driven Macrophage Reprogramming as a Potential Immunometabolic Strategy for Herpes Simplex Keratitis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Interferon-stimulated gene 15 small interfering RNA-loaded polarized mesoporous silica nanocarriers remodel the immune microenvironment to ameliorate post-myocardial infarction heart failure.Materials today. Bio · 2026Article
- ISG15 orchestrates dynamic crosstalk between mitochondrial fat oxidation and type 1 interferon in myeloid cells.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial checkpoint for interferon responses in macrophages.Exploration of targeted anti-tumor therapy · 2026Review
- When ISG15 is involved in inflammation.Frontiers in immunology · 2026Review
- Unraveling the Biology of Interferon-Stimulated Genes: Mechanisms, Functions, and Clinical Implications.Infection and drug resistance · 2026Review
- Organelle-centered ISG15 biology: distinguishing covalent ISGylation from interferon-associated responses.Frontiers in immunology · 2026Review
- IGLC3Frontiers in immunology · 2026Article
- Systemic inflammatory and metabolic disease progression persists despite prevention of myocarditis inFrontiers in immunology · 2026Article
- Review
- ATP functions as a pathogen-associated molecular pattern to activate the E3 ubiquitin ligase RNF213.Nature communications · 2025Article
- Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interferon (IFN)-stimulated gene 15 (ISG15) encodes one of the most abundant proteins induced by interferon, and its expression is associated with antiviral immunity. To identify protein components implicated in IFN and ISG15 signaling, we compared the proteomes of ISG15-/- and ISG15+/+ bone marrow derived macrophages (BMDM) after vaccinia virus (VACV) infection. The results of this analysis revealed that mitochondrial dysfunction and oxidative phosphorylation (OXPHOS) were pathways altered in ISG15-/- BMDM treated with IFN. Mitochondrial respiration, Adenosine triphosphate (ATP) and reactive oxygen species (ROS) production was higher in ISG15+/+ BMDM than in ISG15-/- BMDM following IFN treatment, indicating the involvement of ISG15-dependent mechanisms. An additional consequence of ISG15 depletion was a significant change in macrophage polarization. Although infected ISG15-/- macrophages showed a robust proinflammatory cytokine expression pattern typical of an M1 phenotype, a clear blockade of nitric oxide (NO) production and arginase-1 activation was detected. Accordingly, following IFN treatment, NO release was higher in ISG15+/+ macrophages than in ISG15-/- macrophages concomitant with a decrease in viral titer. Thus, ISG15-/- macrophages were permissive for VACV replication following IFN treatment. In conclusion, our results demonstrate that ISG15 governs the dynamic functionality of mitochondria, specifically, OXPHOS and mitophagy, broadening its physiological role as an antiviral agent.
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