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大蒜新素对人巨细胞病毒体外作用的实验研究:对即刻早期基因的抑制作用

Experimental study on the action of allitridin against human cytomegalovirus in vitro: Inhibitory effects on immediate-early genes.

作者信息

Zhen Hong, Fang Feng, Ye Du-yun, Shu Sai-nan, Zhou Yu-feng, Dong Yong-sui, Nie Xing-cao, Li Ge

机构信息

Laboratory of Pediatric Clinical Virology, Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.

出版信息

Antiviral Res. 2006 Oct;72(1):68-74. doi: 10.1016/j.antiviral.2006.03.017. Epub 2006 Apr 27.

DOI:10.1016/j.antiviral.2006.03.017
PMID:16844239
Abstract

Garlic (Allium sativum) extraction has been reported having anti-HCMV efficacy. This study was aimed to investigate the effect of allitridin (diallyl trisulfide, a compound from A. sativum extraction) on the replication of HCMV and the expression of viral immediate-early genes. In HCMV plaque-reduction assay, allitridin appeared a dose-dependent inhibitory ability with EC(50) value of 4.2 microg/ml (selective index, SI=16.7). Time-of-addition and time-of-removal studies showed that allitridin inhibited HCMV replication in earlier period of viral cycle before viral DNA synthesis. Both immediate early gene (ie1) transcription and IEA (IE(1)72 and IE(2)86) expression was suppressed by allitridin, but not by GCV in a single HCMV cycle format. In addition, allitridin appeared stronger inhibition on IE(2)86 than on IE(1)72. Decrease of viral DNA load in infected cells was also detected under allitridin treatment, probably due to an indirect consequence of the reduction in ie gene transcription. In summary, this study indicated that allitridin has anti-HCMV activity and the mechanism is associated with suppression of ie gene transcription.

摘要

据报道,大蒜(蒜)提取物具有抗人巨细胞病毒(HCMV)的功效。本研究旨在探讨大蒜素(二烯丙基三硫化物,一种来自大蒜提取物的化合物)对HCMV复制及病毒立即早期基因表达的影响。在HCMV蚀斑减少试验中,大蒜素呈现出剂量依赖性抑制能力,其半数效应浓度(EC50)值为4.2微克/毫升(选择性指数,SI = 16.7)。加药时间和撤药时间研究表明,大蒜素在病毒DNA合成之前的病毒周期早期抑制HCMV复制。在单个HCMV周期模式下,大蒜素可抑制立即早期基因(ie1)转录及IEA(IE172和IE286)表达,但更昔洛韦(GCV)无此作用。此外,大蒜素对IE286的抑制作用比对IE172更强。在大蒜素处理下,还检测到感染细胞中病毒DNA载量降低,这可能是ie基因转录减少的间接结果。总之,本研究表明大蒜素具有抗HCMV活性,其机制与抑制ie基因转录有关。

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