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EGCG 通过扰乱脂代谢限制 PRRSV 的增殖。

EGCG Restricts PRRSV Proliferation by Disturbing Lipid Metabolism.

机构信息

College of Veterinary Medicine, Henan Agricultural Universitygrid.108266.b, Zhengzhou, Henan Province, People's Republic of China.

Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs of the People's Republic of China, Zhengzhou, Henan Province, People's Republic of China.

出版信息

Microbiol Spectr. 2022 Apr 27;10(2):e0227621. doi: 10.1128/spectrum.02276-21. Epub 2022 Apr 11.

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) infection leads to late-term reproductive failure and respiratory illness that affect the global swine industry. Epigallocatechin gallate (EGCG) is a polyphenolic compound from green tea that exerts antiviral activity against diverse viruses. This study aimed to report an uncharacterized mechanism of how EGCG restricted PRRSV proliferation. EGCG showed no significant effects on cell viability, cell cycle progression, and apoptosis in porcine alveolar macrophages and MARC-145 cells. The treatment of cells with EGCG attenuated the replication of both highly pathogenic and less pathogenic PRRSV . The viral life cycle analysis demonstrated that EGCG affected PRRSV replication and assembly, but not viral attachment, entry, or release. Interestingly, EGCG treatment abrogated the increased lipid droplets formation and lipid content induced by PRRSV infection. We further demonstrated that EGCG blocked PRRSV-stimulated expression of the key enzymes in lipid synthesis. In addition, EGCG attenuated PRRSV-induced autophagy that is critical for PRRSV proliferation. The supplementation of oleic acid restored PRRSV replication and assembly under EGCG treatment. Together, our results support that EGCG inhibits PRRSV proliferation through disturbing lipid metabolism. Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped single-positive-stranded RNA virus that causes acute respiratory distress in piglets and reproductive failure in sows, resulting in huge economic losses to the global swine industry. Several lines of evidence have suggested the crucial roles of lipids in PRRSV proliferation. Our previous report demonstrated that PRRSV activated lipophagy to facilitate viral replication through downregulating the expression of N-Myc downstream-regulated gene 1. The manipulation of lipid metabolism may be a new perspective to prevent PRRSV spread. In the present study, we reported that epigallocatechin-3-gallate (EGCG), the major component of green tea catechins, significantly attenuated PRRSV infection through inhibiting lipid synthesis and autophagy. Given that natural products derived from plants have helped in the prevention and treatment of various infectious diseases, EGCG has a great potential to serve as a safe and environmentally friendly natural compound to treat PRRSV infection.

摘要

猪繁殖与呼吸综合征病毒(PRRSV)感染可导致晚期生殖失败和呼吸道疾病,影响全球养猪业。表没食子儿茶素没食子酸酯(EGCG)是一种来自绿茶的多酚化合物,对多种病毒具有抗病毒活性。本研究旨在报道 EGCG 限制 PRRSV 增殖的一种未被描述的机制。EGCG 对猪肺泡巨噬细胞和 MARC-145 细胞的细胞活力、细胞周期进程和细胞凋亡没有显著影响。用 EGCG 处理细胞可减弱高致病性和低致病性 PRRSV 的复制。病毒生命周期分析表明,EGCG 影响 PRRSV 复制和组装,但不影响病毒附着、进入或释放。有趣的是,EGCG 处理可消除 PRRSV 感染诱导的脂滴形成和脂质含量增加。我们进一步证明,EGCG 阻断了 PRRSV 刺激的脂质合成关键酶的表达。此外,EGCG 减弱了 PRRSV 诱导的自噬,而自噬对于 PRRSV 的增殖至关重要。油酸的补充恢复了 EGCG 处理下 PRRSV 的复制和组装。综上所述,我们的研究结果支持 EGCG 通过干扰脂质代谢抑制 PRRSV 增殖。猪繁殖与呼吸综合征病毒(PRRSV)是一种包膜的单正链 RNA 病毒,可导致仔猪急性呼吸窘迫和母猪繁殖失败,给全球养猪业造成巨大经济损失。有几条证据表明脂质在 PRRSV 增殖中起着至关重要的作用。我们之前的报告表明,PRRSV 通过下调 N-Myc 下游调节基因 1 的表达来激活脂噬作用,从而促进病毒复制。操纵脂质代谢可能是预防 PRRSV 传播的一个新视角。在本研究中,我们报道表没食子儿茶素-3-没食子酸酯(EGCG),一种绿茶儿茶素的主要成分,通过抑制脂质合成和自噬显著抑制 PRRSV 感染。鉴于植物源性天然产物在预防和治疗各种传染病方面的帮助,EGCG 很有潜力成为一种安全、环保的天然化合物,用于治疗 PRRSV 感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5a4/9045245/9e2728aea7a3/spectrum.02276-21-f001.jpg

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