禽传染性支气管炎病毒诱导的蝰蛇素表达增加,通过限制胆固醇合成抑制病毒复制:一项体外研究。

IF 3.7 1区 农林科学 Q1 VETERINARY SCIENCES
Yu Zhang, Tao-Ni Zhang, Yan-Peng Lu, Li-Na Ren, Sheng-Ting Chen, Ling Liu, Lan-Ping Wei, Ji-Ming Chen, Jian-Ni Huang, Mei-Lan Mo
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引用次数: 0

摘要

随着高突变率和基因组重组导致的新变异株的出现,禽传染性支气管炎病毒(IBV)给全球家禽业造成了巨大的经济损失。人们对 IBV 与宿主相互作用的基本机制知之甚少,尤其是 IBV 如何利用宿主的代谢途径实现病毒的高效复制和传播。本研究探讨了细胞膜、病毒包膜和蝰蛇素介导的胆固醇合成对 IBV 复制的影响。我们的研究结果表明,IBV 感染后胆固醇水平和蝰蛇素的表达明显增加。用甲基-β-环糊精(Methyl-β-cyclodextrin,MβCD)处理细胞,使细胞膜和病毒包膜中的胆固醇急性消耗,明显抑制了IBV的复制;此后,用胆固醇补充细胞膜,成功地恢复了病毒的复制;在感染的早期阶段,直接向细胞膜中添加外源胆固醇明显促进了IBV的感染。此外,过表达蝰蛇素能有效抑制胆固醇的合成以及 IBV 的复制,而敲除蝰蛇素(使用靶向蝰蛇素的 siRNA 进行基因沉默,siViperin)则能显著增加 IBV 的复制和胆固醇水平,而向蝰蛇素转染的细胞补充外源性胆固醇则能明显恢复病毒复制。总之,IBV 感染诱导的蝰蛇素增加通过影响胆固醇的产生在 IBV 复制中发挥了重要作用,为了解 IBV 的发病机制和发现新的潜在抗病毒靶点提供了理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Increased viperin expression induced by avian infectious bronchitis virus inhibits viral replication by restricting cholesterol synthesis: an in vitro study.

With the emergence of new variant strains resulting from high mutation rates and genome recombination, avian infectious bronchitis virus (IBV) has caused significant economic losses to the poultry industry worldwide. Little is known about the underlying mechanisms of IBV-host interactions, particularly how IBV utilizes host metabolic pathways for efficient viral replication and transmission. In the present study, the effects of the cell membrane, viral envelope membrane, and viperin-mediated cholesterol synthesis on IBV replication were explored. Our results revealed significant increase in cholesterol levels and the expression of viperin after IBV infection. Acute cholesterol depletion in the cell membrane and viral envelope membrane by treating cells with methyl-β-cyclodextrin (MβCD) obviously inhibited IBV replication; thereafter, replenishment of the cell membrane with cholesterol successfully restored viral replication, and direct addition of exogenous cholesterol to the cell membrane significantly promoted IBV infection during the early stages of infection. In addition, overexpression of viperin effectively suppressed cholesterol synthesis, as well as IBV replication, whereas knockdown of viperin (gene silencing with siRNA targeting viperin, siViperin) significantly increased IBV replication and cholesterol levels, whereas supplementation with exogenous cholesterol to viperin-transfected cells markedly restored viral replication. In conclusion, the increase in viperin induced by IBV infection plays an important role in IBV replication by affecting cholesterol production, providing a theoretical basis for understanding the pathogenesis of IBV and discovering new potential antiviral targets.

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来源期刊
Veterinary Research
Veterinary Research 农林科学-兽医学
CiteScore
7.00
自引率
4.50%
发文量
92
审稿时长
3 months
期刊介绍: Veterinary Research is an open access journal that publishes high quality and novel research and review articles focusing on all aspects of infectious diseases and host-pathogen interaction in animals.
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