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白藜芦醇通过靶向IE180蛋白抑制伪狂犬病病毒复制。

Resveratrol Inhibits Pseudorabies Virus Replication by Targeting IE180 Protein.

作者信息

Chen Xiangxiu, Song Xu, Li Lixia, Chen Yaqin, Jia Renyong, Zou Yuanfeng, Wan Hongping, Zhao Ling, Tang Huaqiao, Lv Cheng, Zhao Xinghong, Yin Zhongqiong

机构信息

Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China.

出版信息

Front Microbiol. 2022 Jun 2;13:891978. doi: 10.3389/fmicb.2022.891978. eCollection 2022.

Abstract

Resveratrol is a natural polyphenolic product in red wine and peanuts and has many pharmacological activities in humans. Our previous studies showed that resveratrol has good antiviral activity against the pseudorabies virus (PRV). However, little is known about the antiviral mechanism of resveratrol against PRV. In this study, we found that resveratrol inhibited the nuclear localization of IE180 protein, which is an important step for activating early/late genes transcription. Interestingly, the results show that resveratrol inhibited the activity of IE180 protein by dual-luciferase assay. Furthermore, molecular docking analysis shows that resveratrol could bind to the Thr601, Ser603, and Pro606 of IE180 protein. Point mutation assay confirmed that resveratrol lost its inhibition activity against the mutant IE180 protein. The results demonstrate that resveratrol exerts its antiviral activity against PRV by targeting the Thr601/Ser603/Pro606 sites of IE180 protein and inhibiting the transcriptional activation activity of IE180 protein. This study provides a novel insight into the antiviral mechanism of resveratrol against herpes viruses.

摘要

白藜芦醇是红酒和花生中的一种天然多酚类产物,在人体中具有多种药理活性。我们之前的研究表明,白藜芦醇对伪狂犬病病毒(PRV)具有良好的抗病毒活性。然而,关于白藜芦醇抗PRV的抗病毒机制知之甚少。在本研究中,我们发现白藜芦醇抑制了IE180蛋白的核定位,这是激活早期/晚期基因转录的重要步骤。有趣的是,结果表明白藜芦醇通过双荧光素酶测定法抑制了IE180蛋白的活性。此外,分子对接分析表明白藜芦醇可以与IE180蛋白的Thr601、Ser603和Pro606结合。点突变试验证实白藜芦醇对突变型IE180蛋白失去了抑制活性。结果表明,白藜芦醇通过靶向IE180蛋白的Thr601/Ser603/Pro606位点并抑制IE180蛋白的转录激活活性来发挥其对PRV的抗病毒活性。本研究为白藜芦醇抗疱疹病毒的抗病毒机制提供了新的见解。

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