Inhibition of Japanese encephalitis virus infection by nitric oxide: Antiviral effect of nitric oxide on RNA virus replication
Inhibition of Japanese encephalitis virus infection by nitric oxide: Antiviral effect of nitric oxide on RNA virus replication
复制标题
DOI：
10.1128/jvi.71.7.5227-5235.1997
复制
发表时间：
1997-07-01
影响因子：
5.4
通讯作者：
Liao, CL
中科院分区：
文献类型：
--
作者：
Lin, YL;Huang, YL;Liao, CL
研究了一氧化氮（NO）对黄病毒科日本脑炎病毒（JEV）的抗病毒作用。体外实验表明，γ-干扰素激活的RAW 264.7小鼠巨噬细胞对JEV复制的抑制作用与细胞内NO的产生有关。γ-干扰素激活的RAW 264.7细胞也有效地阻碍了JEV在邻近旁观者中的复制，并且这种抗JEV作用可以被NO合酶（NOS）抑制剂N-单甲基-L-精氨酸乙酸酯逆转。在体内，当NOS活性被竞争性抑制剂N-硝基-L-精氨酸甲酯抑制时，JEV感染小鼠的死亡率增加。此外，当使用有机供体S-硝基-N-乙酰青霉胺（SNAP）时，在最初感染JEV的N18、人神经元NT-2和BHK-21细胞中，以及在持续感染JEV的C2-2细胞中也观察到NO介导的抗病毒作用，这些数据再次证实NO对多种细胞内病原体具有有效和广谱的抗微生物活性。有趣的是，在JEV感染之前用SNAP处理N18细胞并不能增强NO的抗病毒作用，该措施已经显示在水泡性口炎病毒感染中大大增加NO的抗病毒作用。从NO对细胞培养物中JEV复制的影响的生物化学分析，NO对病毒RNA合成、病毒蛋白积累和病毒从感染细胞中释放有明显的抑制作用，提示NO可能在宿主的先天免疫中起重要作用，从而限制了JEV在中枢神经系统感染的初始阶段。
The antiviral effects of nitric oxide (NO) on Japanese encephalitis virus (JEV), a member of the family Flaviviridae, were investigated in this study, In vitro, inhibition of replication of JEV in gamma interferon-activated RAW 264.7 murine macrophages was correlated to cellular NO production, When cocultured with infected murine neuroblastoma N18 cells, gamma interferon-activated RAW 264.7 cells also efficiently hindered JEV replication in contiguous bystanders, and this anti-JEV effect could be reversed by an NO synthase (NOS) inhibitor, N-monomethyl-L-arginine acetate, In vivo, the mortality rate increased as the NOS activity of JEV-infected mice was inhibited by its competitive inhibitor, N-nitro-L-arginine methyl ester, Moreover, when an organic donor, S-nitro-N-acetylpenicillamine (SNAP), was used, the NO-mediated antiviral effect was also observed in primarily JEV-infected N18, human neuronal NT-2, and BHK-21 cells, as well as in persistently JEV-infected C2-2 cells, These data reaffirm that NO has an effective and broad-spectrum antimicrobial activity against diversified intracellular pathogens, Interestingly, the antiviral effect of NO was not enhanced by treatment of N18 cells with SNAP prior to JEV infection, a measure which has been shown to greatly increase the antiviral effect of NO in infection by vesicular stomatitis virus, From biochemical analysis of the impact of NO on JEV replication in cell culture, NO was found to profoundly inhibit viral RNA synthesis, viral protein accumulation, and virus release from infected cells, The results herein thus suggest that NO may play a crucial role in the innate immunity of the host to restrict the initial stage of JEV infection in the central nervous system.