An antiviral effect of nitric oxide: inhibition of reovirus replication

We have previously shown that macrophages from chickens infected with avian reovirus are primed to produce nitric oxide (NO) in response to T cell cytokines and bacterial lipopolysaccharide (LPS). We now show that NO exerts potent antireovirus effects. Reovirus replication was substantially reduced in a chicken macrophage cell line, HD11, induced to make NO by stimulation with LPS or conditioned medium from concanavalin A-stimulated spleen cells. The use of a competitive inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine, reduced the antiviral effect of LPS-stimulated HD11 cells. Cytostatic effects were concurrent with the observed antiviral effects of NO. Among these cytostatic effects were reduction in DNA synthesis, protein synthesis, and mitochondrial metabolism. These results indicated that a potential consequence of macrophage priming following virus infection is the protection of cells against virus-induced replication and cytopathic effects, and this protection may be mediated by the cytostatic effects of NO on the host cell.