Akademik Veri Yönetim Sistemi
Journal of General Virology, cilt.78, sa.1, ss.195-203, 1997 (SCI-Expanded)
We have analysed the ability of herpes simplex virus type 2 (HSV-2) to induce nitric oxide (NO) production in resting BALB/c mouse peritoneal macrophages. In most experiments, macrophages produced very small amounts of NO upon infection with HSV-2. Mock virus preparations did not induce NO production, and virus inactivation experiments showed that infectious virus was required. Since interferon-γ (IFN-γ) is the prototype cytokine that is able to induce significant NO production in macrophages, we found it of interest to examine the influence of HSV-2 infection on the IFN-γ-induced NO production. The virus exerted a synergistic effect on the IFN-γ-induced NO release, which was accompanied by induction of the iNOS-gene as revealed by RT-PCR. This effect was largely dependent on the presence of infectious virus particles, since only a minor effect was seen with mock virus and inactivated virus preparations. From experiments with neutralizing antibodies to tumour necrosis factor-α (TNF-α) and IFN-α/β it was concluded that the synergistic effect is dependent on autocrine secretion of TNF-α, which acts as a second signal and synergizes with IFN-γ in NO production.