Herpes simplex virus type 2 synergizes with interferon-gamma in the induction of nitric oxide production in mouse macrophages through autocrine secretion of tumour necrosis factor-alpha.
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-gamma (IFN-gamma) 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-gamma-induced NO production. The virus exerted a synergistic effect on the IFN-gamma-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-alpha (TNF-alpha) and IFN-alpha/beta it was concluded that the synergistic effect is dependent on autocrine secretion of TNF-alpha, which acts as a second signal and synergizes with IFN-gamma in NO production.
Baskin
H
H
Department of Medical Microbiology and Immunology, University of Aarhus, Denmark.
Ellermann-Eriksen
S
S
Lovmand
J
J
Mogensen
S C
SC
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D017931:DNA Primers; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins; D018139:Simplexvirus / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014709:Vero Cells
D017931:DNA Primers; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase