Inhibition of influenza virus replication by nitric oxide

Nitric oxide (NO) has been shown to contribute to the pathogenesis of influenza virus-induced pneumonia in mouse models. Here we show that replication of influenza A and B viruses in Mabin Darby canine kidney cells is severely impaired by the NO donor, S-nitroso-N-acetylpenicillamine. Reduction of productively infected cells and virus production proved to correlate with inhibition of viral RNA synthesis, indicating that NO affects an early step in the replication cycle of influenza viruses. Nitric oxide (NO), a gaseous free radical has been shown to have multiple biological functions. NO is catalytically gener-ated by one of the three isoforms of NO synthase (NOS) from L-arginine. eNOS and nNOS, which are produced in endothe-lial cells and neuronal cells, have been shown to play a role in vasodilatation and neurotransmission, respectively, whereas NO generated by iNOS (NOS2), the inducible form of NOS, has been shown to play a role in the defense against a variety of microbial pathogens, including bacteria, parasites (for a review, see reference 24), and viruses, including herpes simplex virus type 1 (HSV-1), vesicular stomatitis virus, Japanese en-cephalitis virus, poliovirus, murine hepatitis virus, murine leu-kemia virus, coxsackievirus, ectromelia virus, rhinovirus, an