Role of Indoleamine 2,3-Dioxygenase in Antiviral Activity of Interferon-γ Against Vaccinia Virus

Interferon-γ (IFN-γ) 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-γ in both in vivo and in vitro experiments. In macrophages, inhibition of replication of poxviruses by IFN-γ 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-γ against vaccinia virus. L-tryptophan, an inhibitor of IDO, completely blocked the antiviral activity of IFN-γ 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-γ. IFN-γ may use different antiviral mechanisms in different cell types.