Role of nitric oxide synthase type 2 in acute infection with murine cytomegalovirus

Whether or not NO plays a critical role in murine CMV (MCMV) infection has Set to be elucidated. In this study, we examined the role of NO in acute in fection with MCMV using NO synthase type 2 (NOS2)-deficient mice. NOS2(-/-) mice were more susceptible to lethal infection with MCMV than NOS2(+/+) mi ce and generated a much higher peak virus titer in the salivary gland after acute infection. A moderate increase in the MCMV titer was also observed i n other organs of NOS2(-/-) mice such as the spleen, lung, and liver. The i mmune responses to MCMV infection including NK cell cytotoxicity and CTL re sponse in NOS2(-/-) mice were comparable with those of NOS2(+/+) mice. More over, the ability to produce IFN-gamma is not impaired in NOS2(-/-) mice af ter MCMV infection. The peritoneal macrophages from NOS2(-/-) mice, however , exhibited a lower antiviral activity than those from NOS2(+/+) mice, resu lting in an enhanced viral replication in macrophages themselves, Treatment of these cells from NOS2(+/+) mice with a selective NOS2 inhibitor decreas ed the antiviral activity to a level below that obtained with NOS2(-/-) mic e. In addition, the absence of NOS2 and NOS2-mediated antiviral activity of macrophages resulted in not only an enhanced MCMV replication and a high m ortality but also a consequent risk of the latency. It was thus concluded t hat the NOS2-mediated antiviral activity of macrophages via NO plays a prot ective role against MCMV infection at an early and late stage of the infect ion.