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IFN-γ-mediated control of SARS-CoV-2 infection through nitric oxide

Silva et al., Frontiers in Immunology, doi:10.3389/fimmu.2023.1284148
Dec 2023  
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In vitro study showing that treatment with interferon-gamma (IFN-γ) inhibits SARS-CoV-2 infection in simian Vero E6 and human lung epithelial cell lines. The IFN-γ-triggered antiviral effect against SARS-CoV-2 is mediated through the endogenous production of nitric oxide (NO). IFN-γ alone or together with IL-1β induces NO production and reduces SARS-CoV-2 replication. Pharmacologic inhibition of NO production prevents the IFN-γ-induced antiviral activity. As IFN-γ is produced by CD8+ T cells in early response to SARS-CoV-2, these findings link the T cell-mediated adaptive immune response to a NO-dependent innate antiviral pathway in the host defense against SARS-CoV-2 infection. Authors believe that NO-mediated antiviral effects may be intracellular.
Silva et al., 15 Dec 2023, USA, peer-reviewed, 9 authors. Contact:
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperNitric OxideAll
IFN-γ-mediated control of SARS-CoV-2 infection through nitric oxide
Bruno J De Andrade Silva, Paul A Krogstad, Rosane M B Teles, Priscila R Andrade, Jacob Rajfer, Monica G Ferrini, Otto O Yang, Barry R Bloom, Robert L Modlin
Frontiers in Immunology, doi:10.3389/fimmu.2023.1284148
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-g), which, when administered to infected patients, is reported to result in viral clearance and resolution of pulmonary symptoms. IFN-g 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-g has been shown to trigger antiviral activity via the generation of nitric oxide (NO), we investigated whether IFN-g 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-g 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-1b) on the IFN-g-induced NO production and its antiviral efficacy. Results: Treatment of Vero E6 cells with IFN-g 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-g also triggered a NO-mediated antiviral activity in SARS-CoV-2 infected human lung epithelial cell lines A549-ACE2 and Calu-3. IL-1b enhanced IFN-g 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,
Ethics statement Ethical approval was not required for the studies on humans in accordance with the local legislation and institutional requirements because only commercially available established cell lines were used. Author contributions Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Supplementary material The Supplementary Material for this article can be found online at: full#supplementary-material
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