Nitric oxide and viral infection: No antiviral activity against a flavivirus in vitro, and evidence for contribution to pathogenesis in experimental infection in vivo
Nitric oxide and viral infection: No antiviral activity against a flavivirus in vitro, and evidence for contribution to pathogenesis in experimental infection in vivo
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DOI：
10.1006/viro.1996.0252
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发表时间：
1996-05-01
期刊：
影响因子：
3.7
通讯作者：
Eibl, MM
中科院分区：
文献类型：
--
作者：
Kreil, TR;Eibl, MM
受到刺激后，小鼠巨噬细胞会产生高水平的一氧化氮（NO），这是一种有效的杀菌和杀肿瘤剂，最近也被认为是抗病毒防御的介质。由于 NO 的产生失调可能会导致广泛的组织损伤，因此这种强大介质的产生受到严格调节。然而，病毒感染可能会改变某些巨噬细胞功能的调节，我们小组最近的工作表明，病毒感染（通过诱导干扰素-αβ合成）可能会引发或下调 NO 的产生。鉴于 NO 的抗病毒活性，病毒感染中 NO 产生的下调似乎与抗病毒防御相矛盾。然而，正如其他人提供的证据表明 NO 的产生可能有助于几种嗜神经病毒感染的发病机制一样，我们在体外和体内研究了小鼠巨噬细胞和感染蜱传脑炎病毒（TBE-V）（一种黄病毒）的 BALB/c 小鼠中 NO 产生的作用。来自 TBE-V 感染小鼠的巨噬细胞在体外培养时自发产生 NO，但来自对照小鼠的巨噬细胞则不然。与NO对几种痘病毒和单纯疱疹病毒复制的抑制作用相反，高水平的NO产生对体外TBE-V复制没有表现出抑制作用。最后，对 TBE-V 感染的小鼠体内给予 NO 产生的竞争性抑制剂氨基胍，显着延长了它们的平均生存时间。因此，我们的结果表明，NO 的体外抗病毒活性可能仅限于某些病毒，而其他病毒则不受影响。此外，我们提供的证据表明，NO 的产生甚至可能有助于体内病毒感染的发病机制。 (C) 1996 学术出版社
Upon stimulation murine macrophages produce high levels of nitric oxide (NO), a potent microbicidal and tumoricidal agent recently also implicated as a mediator of antiviral defense. As dysregulated production of NO may lead to extensive tissue damage, the production of this powerful mediator is tightly regulated. Viral infection, however, may alter the regulation of certain macrophage functions, and recent work from our group demonstrated that viral infection-via induction of interferon-alpha beta synthesis-may either prime for or down-modulate NO production. In light of antiviral activities of NO, down-modulation of NO production in viral infection would seem contradictory to antiviral defense. As others, however, have provided evidence that NO production may contribute to pathogenesis of infection with several neurotropic viruses, the role of NO production was investigated in vitro and in vivo in murine macrophages and in BALB/c mice infected with tick-borne encephalitis virus (TBE-V), a flavivirus. Macrophages from TBE-V-infected mice, but not from control mice, spontaneously produced NO upon culture in vitro. In contrast to the inhibitory effect of NO on replication of several poxviruses and herpes simplex virus, high levels of NO production did not display an inhibitory influence on TBE-V replication in vitro. And finally, in vivo administration of a competitive inhibitor of NO production, aminoguanidine, to TBE-V-infected mice significantly increased their mean survival time. Our results thus demonstrate that the antiviral activity of NO in vitro may be confined to certain viruses, whereas others remain unaffected. Furthermore, we provide evidence that NO production may even contribute to pathogenesis of viral infection in vivo. (C) 1996 Academic Press, Inc.