Inhibition of influenza virus replication by nitric oxide

Abstract

Background: Upon infection with influenza viruses, patients develop a cytokine response including the induction of IFN-γ, TNF-α and IL-1β. These cytokines are known to induce the expression of the inducible form of nitric oxide (NO) synthase (iNOS) in human airway epithelial cells. NO has been shown to exert antiviral activity against a number of different viruses. It is unknown, however, whether NO has antiviral properties against influenza viruses. Methods: The effect of the NO-donor S-nitroso- N-acetylpenicillamine (SNAP) was studied on the influenza virus replication in Madin Darby Canine Kidney (MDCK) cells. To measure influenza virus replication, IFA, hemagglutination assays, measurement of infectious virus in culture supernatants and RNA hybridization techniques were performed. Results: SNAP was found to inhibit influenza virus replication in a dose-dependent manner. NO liberated from SNAP inhibited the synthesis of vRNA and mRNA encoding viral proteins severely. Subsequently, fewer influenza-infected cells were detected by IFA and the titer of infectious virus in culture supernatants of infected SNAP treated MDCK cells were reduced. Conclusion: It is concluded that NO inhibits the replication of influenza viruses, probably during the early steps of the virus replication cycle, involving the synthesis of vRNA and mRNA encoding viral proteins. Therefore, it is hypothesized that the production of NO by cytokine-induced iNOS in airway epithelial cells provides an antiviral effect in these cells.