INHIBITION OF VIRAL REPLICATION BY INTERFERON-GAMMA-INDUCED NITRIC-OXIDE SYNTHASE
INHIBITION OF VIRAL REPLICATION BY INTERFERON-GAMMA-INDUCED NITRIC-OXIDE SYNTHASE
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DOI：
10.1126/science.7690156
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发表时间：
1993-09-10
期刊：
影响因子：
56.9
通讯作者：
MACMICKING, JD
中科院分区：
文献类型：
--
作者：
KARUPIAH, G;XIE, QW;MACMICKING, JD
干扰素（IFN）在许多细胞类型中诱导抗病毒活性。IFN-γ抑制小鼠巨噬细胞中鼠肢畸形、牛痘和单纯疱疹病毒-1复制的能力与细胞产生一氧化氮（NO）有关。在暴露于NO合酶抑制剂的IFN-γ处理的巨噬细胞中恢复病毒复制。相反，没有检测到NO合成的上皮细胞限制病毒复制时，转染的互补DNA编码诱导型NO合酶或有机化合物，产生NO。在小鼠中，NO合酶的抑制剂转化为暴发性鼠痘病毒感染解决ectromelia。因此，NO合酶的诱导对于IFN-γ的实质性抗病毒作用可能是必要的和足够的。
Interferons (IFNs) induce antiviral activity in many cell types. The ability of IFN-gamma to inhibit replication of ectromelia, vaccinia, and herpes simplex-1 viruses in mouse macrophages correlated with the cells' production of nitric oxide (NO). Viral replication was restored in IFN-gamma-treated macrophages exposed to inhibitors of NO synthase. Conversely, epithelial cells with no detectable NO synthesis restricted viral replication when transfected with a complementary DNA encoding inducible NO synthase or treated with organic compounds that generate NO. In mice, an inhibitor of NO synthase converted resolving ectromelia virus infection into fulminant mousepox. Thus, induction of NO synthase can be necessary and sufficient for a substantial antiviral effect of IFN-gamma.