Simon M, Falk K I, Lundkvist A, Mirazimi A
Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden.
Virus Res. 2006 Sep;120(1-2):184-90. doi: 10.1016/j.virusres.2006.03.005. Epub 2006 May 2.
Crimean Congo hemorrhagic fever virus (CCHFV) is a geographically widespread pathogen that causes severe hemorrhagic fever with high mortality. Even though one of the main objectives focuses on the progress of antiviral agents, the research on CCHFV is strongly hampered due to its BSL-4 classification. Nitric oxide (NO), a mediator with broad biological effects, has been shown to possess inhibitory properties against various pathogens. The molecule constitutes a component of the innate immunity and serves to assist in the early immunological events where it contributes to clearance of microorganisms. In this study, we investigated the inhibitory properties of exogenous NO on CCHFV. We found that NO had a significant antiviral activity against CCHFV replication. By using the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) we were able to show up to 99% reduction in virion progeny yield. In contrast, 3-morpholinosydnonimine hydrochloride (SIN-1), a peroxynitrite donor, had no significant antiviral activity against CCHFV. Furthermore the expression of viral proteins; the nucleocapsid protein and the glycoprotein, were clearly reduced with increasing concentrations of SNAP. We have also shown that the amount of total vRNA in SNAP-treated cells was reduced by about 50% compared to the controls.
克里米亚刚果出血热病毒（CCHFV）是一种在地理上广泛传播的病原体，可引起严重出血热，死亡率很高。尽管主要目标之一集中在抗病毒药物的进展上，但由于其生物安全4级分类，对CCHFV的研究受到了严重阻碍。一氧化氮（NO）是一种具有广泛生物学效应的介质，已被证明对多种病原体具有抑制特性。该分子是先天免疫的一个组成部分，有助于早期免疫事件，在其中促进微生物的清除。在本研究中，我们研究了外源性NO对CCHFV的抑制特性。我们发现NO对CCHFV复制具有显著的抗病毒活性。通过使用NO供体S-亚硝基-N-乙酰青霉胺（SNAP），我们能够使子代病毒粒子产量降低高达99%。相比之下，过氧亚硝酸盐供体盐酸3-吗啉代辛二亚胺（SIN-1）对CCHFV没有显著的抗病毒活性。此外，随着SNAP浓度的增加，病毒蛋白核衣壳蛋白和糖蛋白的表达明显降低。我们还表明，与对照组相比，SNAP处理细胞中的总病毒RNA量减少了约50%。
