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

• DOI: 10.3389/fimmu.2023.1284148
• Publication Date: 2023-12-15T10:32:02Z
• Authors: Bruno J. de Andra...; Paul A. Krogstad; Rosane M. B. Teles; Priscila R. Andrade; Jacob Rajfer; Monica G. Ferrini; Otto O. Yang; Barry R. Bloom; Robert L. Modlin
• Keywords: Vero cell

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 infected patients, reported result in viral clearance and resolution pulmonary symptoms. IFN-γ treatment a human lung epithelial cell line triggered an activity SARS-CoV-2, yet mechanism for this response was not identified. Methods Given that been shown trigger via generation nitric oxide (NO), we investigated whether induction SARS-CoV-2 infection dependent upon NO cells. We treated simian Vero E6 lines, including A549-ACE2, Calu-3, with observed resulting its effects on replication. Pharmacological inhibition inducible synthase (iNOS) employed assess dependency production. Additionally, study examined effect interleukin-1b (IL-1β) IFN-g-induced production efficacy. Results Treatment cells resulted dose-responsive inhibitory This blocked by pharmacologic iNOS. also NO-mediated lines A549-ACE2 Calu-3. IL-1β enhanced NO, but it had little activity. Discussion IFN-g be produced CD8+ T early our findings IFN-γ-triggered, NO-dependent, links adaptive immune innate pathway These results underscore importance provide insights into potential therapeutic strategies COVID-19.