ArticleFrontiers in immunology2023
IFN-γ-mediated control of SARS-CoV-2 infection through nitric oxide.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Nitric oxide drives proteomic diversity through alternative splicing.Molecular cell · 2026Article
- Enhancement of simeprevir and sofosbuvir anti-ZIKV activity by iNOS-derived NO in vitroFIRST REVIEW ROUND - REVIEWERS' COMMENTSREVIEWERS' COMMENTS.Memorias do Instituto Oswaldo Cruz · 2026Article
- CXCR3 ameliorates neutrophil-dependent disease severity in SARS-CoV-2 infection by regulating CD4Frontiers in immunology · 2026Article
- MUC1 in the upper-lower airway inflammatory continuum: an endotype-centered perspective.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Obesity Risk Factors Promote Metabolic Reprogramming and Viral Infection in Airways with Type 1 High Inflammation.Biomolecules · 2025Article
- Impact of Maternal Exposure to SARS-CoV-2 on Immunological Components of Breast Milk.International journal of molecular sciences · 2025Review
- IFN-γ derived from activated human CD4Scientific reports · 2024Article
- Potential Beneficial Role of Nitric Oxide in SARS-CoV-2 Infection: Beyond Spike-Binding Inhibition.Antioxidants (Basel, Switzerland) · 2024Article
- IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques.PLoS pathogens · 2024Article
- IRF1 Mediates Growth Arrest and the Induction of a Secretory Phenotype in Alveolar Epithelial Cells in Response to Inflammatory Cytokines IFNγ/TNFα.International journal of molecular sciences · 2024Article
- Protective interplay:Frontiers in immunology · 2024Article
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Authors and funding
9 authors.
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Abstract
Introduction: The COVID-19 pandemic has highlighted the need to identify mechanisms of antiviral host defense against SARS-CoV-2. One such mediator is interferon-g (IFN-γ), which, when administered to infected patients, is reported to result in viral clearance and resolution of pulmonary symptoms. IFN-γ treatment of a human lung epithelial cell line triggered an antiviral activity against SARS-CoV-2, yet the mechanism for this antiviral response was not identified. Methods: Given that IFN-γ has been shown to trigger antiviral activity via the generation of nitric oxide (NO), we investigated whether IFN-γ induction of antiviral activity against SARS-CoV-2 infection is dependent upon the generation of NO in human pulmonary epithelial cells. We treated the simian epithelial cell line Vero E6 and human pulmonary epithelial cell lines, including A549-ACE2, and Calu-3, with IFN-γ and observed the resulting induction of NO and its effects on SARS-CoV-2 replication. Pharmacological inhibition of inducible nitric oxide synthase (iNOS) was employed to assess the dependency on NO production. Additionally, the study examined the effect of interleukin-1b (IL-1β) on the IFN-g-induced NO production and its antiviral efficacy. Results: Treatment of Vero E6 cells with IFN-γ resulted in a dose-responsive induction of NO and an inhibitory effect on SARS-CoV-2 replication. This antiviral activity was blocked by pharmacologic inhibition of iNOS. IFN-γ also triggered a NO-mediated antiviral activity in SARS-CoV-2 infected human lung epithelial cell lines A549-ACE2 and Calu-3. IL-1β enhanced IFN-γ induction of NO, but it had little effect on antiviral activity. Discussion: Given that IFN-g has been shown to be produced by CD8+ T cells in the early response to SARS-CoV-2, our findings in human lung epithelial cell lines, of an IFN-γ-triggered, NO-dependent, links the adaptive immune response to an innate antiviral pathway in host defense against SARS-CoV-2. These results underscore the importance of IFN-γ and NO in the antiviral response and provide insights into potential therapeutic strategies for COVID-19.
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