Shah Mahmud Raihan, Müller Christin, Romanova Yulia, Mostafa Ahmed, Ulyanova Vera, Pleschka Stephan, Ilinskaya Olga
Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremlevskaya Street 18, Kazan 420008, Russia.
Institute of Medical Virology, Justus Liebig University, Schubert Street 81, 35392 Giessen, Germany.
Biomed Res Int. 2017;2017:5279065. doi: 10.1155/2017/5279065. Epub 2017 May 4.
ribonuclease (binase) was shown to be a promising antiviral agent in animal models and cell cultures. However, the mode of its antiviral action remains unknown. To assess the binase effect on intracellular viral RNA we have selected single stranded negative- and positive-sense RNA viruses, influenza virus, and rhinovirus, respectively, which annually cause respiratory illnesses and are characterized by high contagious nature, mutation rate, and antigen variability. We have shown that binase exerts an antiviral effect on both viruses at the same concentration, which does not alter the spectrum of A549 cellular proteins and expression of housekeeping genes. The titers of influenza A (H1N1pdm) virus and human rhinovirus serotype 1A were reduced by 40% and 65%, respectively. A preincubation of influenza virus with binase before infection significantly reduced viral titer after single-cycle replication of the virus. Using influenza A virus mini genome system we showed that binase reduced GFP reporter signaling indicating a binase action on the expression of viral mRNA. Binase reduced the level of H1N1pdm viral NP mRNA accumulation in A549 cells by 20%. Since the viral mRNA is a possible target for binase this agent could be potentially applied in the antiviral therapy against both negative- and positive-sense RNA viruses.
在动物模型和细胞培养中，核糖核酸酶（binase）被证明是一种有前景的抗病毒剂。然而，其抗病毒作用模式仍不清楚。为了评估binase对细胞内病毒RNA的影响，我们分别选择了单链负链和正链RNA病毒、流感病毒和鼻病毒，这些病毒每年都会引起呼吸道疾病，具有高传染性、突变率和抗原变异性的特点。我们已经表明，binase在相同浓度下对两种病毒都有抗病毒作用，且不会改变A549细胞蛋白谱和管家基因的表达。甲型流感（H1N1pdm）病毒和1A型人鼻病毒的滴度分别降低了40%和65%。在感染前将流感病毒与binase预孵育，可显著降低病毒单循环复制后的病毒滴度。使用甲型流感病毒微型基因组系统，我们表明binase降低了绿色荧光蛋白（GFP）报告信号，表明binase对病毒mRNA的表达有作用。Binase使A549细胞中H1N1pdm病毒NP mRNA的积累水平降低了20%。由于病毒mRNA可能是binase的作用靶点，这种药物可能潜在地应用于针对负链和正链RNA病毒的抗病毒治疗。
