ArticleSignal transduction and targeted therapy2023
SARS-CoV-2 spike protein induces IL-18-mediated cardiopulmonary inflammation via reduced mitophagy.
Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 64 citations in OpenAlex.
- Mitophagy in pathogenesis and therapeutic implications for infection.Experimental & molecular medicine · 2026Review
- Mitophagy-mediated immune evasion: Shared strategies of pathogens.Redox biology · 2026Review
- Exploring Key Regulators of Mitochondrial Dynamics and Immune Response in SARS-CoV-2 Infection.Viruses · 2026Article
- Efferocytosis of apoptotic bodies drives SARS-CoV-2 infection and macrophage inflammation.Nature communications · 2026Article
- Coronavirus infectious bronchitis virus spike protein inhibits FUNDC1-mediated mitophagy to prevent nucleocapsid protein degradation.Journal of virology · 2026Article
- Restricting intracellularAutophagy · 2026Article
- NEAT1 drives SARS-CoV-2 N protein-induced inflammation, metabolic reprogramming, and mitochondria-ER stress crosstalk.Scientific reports · 2026Article
- SARS-CoV-2 damages cardiomyocyte mitochondria and implicates long COVID-associated cardiovascular manifestations.Journal of advanced research · 2026Article
- Interleukins in COVID-19 and SARS-CoV-2 Variants: Immunopathogenesis, Therapeutic Perspectives and Vaccine-Induced Immune Responses.International journal of molecular sciences · 2026Review
- Recombinant SARS-Cov-2 spike protein S1 subunit upregulates P2 × 7-NLRP3 leading to macrophage pyroptosis promoting acute lung injury.Respiratory research · 2026Article
- A novel strategy for the protective effect of ginsenoside Rg1 against ovarian reserve decline by the PINK1 pathway.Pharmaceutical biology · 2025Article
- A data-driven sliding-window pairwise comparative approach for the estimation of transmission fitness of SARS-CoV-2 variants and construction of the evolution fitness landscape.Quantitative biology (Beijing, China) · 2025Article
- Impaired Peripheral Blood Mononuclear Cell (PBMC) Mitochondrial Respiration Is Associated with Mortality and Long COVID Syndrome Severity in COVID-19 Patients.International journal of molecular sciences · 2025Article
- Double-edged mitophagy: balancing inflammation and resolution in lung disease.Clinical science (London, England : 1979) · 2025Review
- Mitochondrial Reactive Oxygen Species: A Unifying Mechanism in Long COVID and Spike Protein-Associated Injury: A Narrative Review.Biomolecules · 2025Review
- The role of SARS-CoV-2 main protease in innate immune regulation: From molecular mechanisms to therapeutic implications.Acta pharmaceutica Sinica. B · 2025Review
- Identification of reactive CpGs and RNA expression in early COVID-19 through cis-eQTM analysis reflecting disease severity and recovery.Communications biology · 2025Article
- Profile of Cytokines Associated with SARS-CoV2 Seropositivity in Multiple Sclerosis Patients and Its Persistence over Six Months.Journal of clinical medicine · 2025Article
- Elevated Plasma Levels of NET Components in Men with Severe COVID-19 Correlates to Increased Amounts of IL-18.European journal of immunology · 2025Article
- Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
Cardiopulmonary complications are major drivers of mortality caused by the SARS-CoV-2 virus. Interleukin-18, an inflammasome-induced cytokine, has emerged as a novel mediator of cardiopulmonary pathologies but its regulation via SARS-CoV-2 signaling remains unknown. Based on a screening panel, IL-18 was identified amongst 19 cytokines to stratify mortality and hospitalization burden in patients hospitalized with COVID-19. Supporting clinical data, administration of SARS-CoV-2 Spike 1 (S1) glycoprotein or receptor-binding domain (RBD) proteins into human angiotensin-converting enzyme 2 (hACE2) transgenic mice induced cardiac fibrosis and dysfunction associated with higher NF-κB phosphorylation (pNF-κB) and cardiopulmonary-derived IL-18 and NLRP3 expression. IL-18 inhibition via IL-18BP resulted in decreased cardiac pNF-κB and improved cardiac fibrosis and dysfunction in S1- or RBD-exposed hACE2 mice. Through in vivo and in vitro work, both S1 and RBD proteins induced NLRP3 inflammasome and IL-18 expression by inhibiting mitophagy and increasing mitochondrial reactive oxygenation species. Enhancing mitophagy prevented Spike protein-mediated IL-18 expression. Moreover, IL-18 inhibition reduced Spike protein-mediated pNF-κB and EC permeability. Overall, the link between reduced mitophagy and inflammasome activation represents a novel mechanism during COVID-19 pathogenesis and suggests IL-18 and mitophagy as potential therapeutic targets.
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