Role of Indoleamine 2,3-Dioxygenase in Antiviral Activity of Interferon-gamma Against Vaccinia Virus.
Interferon-gamma (IFN-gamma) has antiviral activity against poxviruses as well as many other viruses, bacteria and a parasite, Toxoplasma gondii. Inducible nitric oxide synthase (NOS2) has been shown to mediate the antiviral activity of IFN-gamma in both in vivo and in vitro experiments. In macrophages, inhibition of replication of poxviruses by IFN-gamma is NOS2-dependent. In this report we tested nonmacrophage cell lines and found that indoleamine 2,3-dioxygenase (IDO) also mediated the antiviral activity of IFN-gamma against vaccinia virus. L-tryptophan, an inhibitor of IDO, completely blocked the antiviral activity of IFN-gamma against vaccinia virus in 143B cells, an human osteosarcoma cell line, whereas N(G)-methyl-L-arginine, a NOS2 inhibitor, did not. IDO may account for the NOS2-independent antiviral mechanism induced by IFN-gamma. IFN-gamma may use different antiviral mechanisms in different cell types.
Terajima
Masanori
M
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. Masanori.Terajima@umassmed.edu
Leporati
Anita M
AM
D000998:Antiviral Agents / Q000494:pharmacology; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014364:Tryptophan / Q000494:pharmacology; D014616:Vaccinia virus / Q000187:drug effects / Q000254:growth & development*; D010948:Viral Plaque Assay; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019323:omega-N-Methylarginine; D007371:Interferon-gamma; D014364:Tryptophan; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II