吲哚胺2,3-双加氧酶在γ干扰素抗痘苗病毒活性中的作用

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

作者信息

Terajima Masanori, Leporati Anita M

机构信息

Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.

出版信息

Viral Immunol. 2005;18(4):722-9. doi: 10.1089/vim.2005.18.722.

DOI:10.1089/vim.2005.18.722

PMID:16359238

Abstract

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.

摘要

干扰素-γ（IFN-γ）对痘病毒以及许多其他病毒、细菌和一种寄生虫——弓形虫具有抗病毒活性。在体内和体外实验中均已表明，诱导型一氧化氮合酶（NOS2）介导IFN-γ的抗病毒活性。在巨噬细胞中，IFN-γ对痘病毒复制的抑制作用依赖于NOS2。在本报告中，我们对非巨噬细胞系进行了测试，发现吲哚胺2,3-双加氧酶（IDO）也介导IFN-γ针对痘苗病毒的抗病毒活性。IDO的抑制剂L-色氨酸完全阻断了IFN-γ对人骨肉瘤细胞系143B细胞中痘苗病毒的抗病毒活性，而NOS2抑制剂N(G)-甲基-L-精氨酸则没有。IDO可能解释了IFN-γ诱导的不依赖NOS2的抗病毒机制。IFN-γ可能在不同细胞类型中使用不同的抗病毒机制。