Nitric oxide production is increased during murine vaccinia virus infection, but may not be essential for virus clearance

Recent reports have highlighted a potential antiviral activity for nitric oxide (NO). The purpose of this study was to investigate the production of NO in mice during vaccinia virus (VV) or herpes simplex virus type 1 infection, and to assess the role of NO in clearance of VV. Reactive nitrogen intermediates (RNI; NO and its stable oxidation products, nitrite and nitrate) were significantly elevated in the plasma of mice infected with these viruses. Furthermore, spleen cells from virus-infected mice produced elevated RNI levels following stimulation in vitro with LPS. NO production during VV infection was critically dependent on the cytokines tumor necrosis factor and interferon-gamma, and on the presence of both CD4(+) and CD8(+) T lymphocytes. Treatment of VV-infected mice with the nitric oxide synthase inhibitor N-G-methyl-L-arginine did not alter the course of infection, suggesting that NO may not be essential for the clearance of this virus. (C) lees Academic Press, Inc.