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 nit ric oxide (NO). The purpose of this study was to investigate the produ ction 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. Re active nitrogen intermediates (RNI; NO and its stable oxidation produc ts, 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 v itro with LPS. NO production during VV infection was critically depend ent on the cytokines tumor necrosis factor and interferon-gamma, and o n the presence of both CD4(+) and CD8(+) T lymphocytes. Treatment of V V-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 P ress, Inc.