绒源新城疫病毒的血凝素-神经氨酸酶蛋白通过 NF-κB 介导的程序性细胞死亡增强病毒感染。

IF 3.7 1区 农林科学 Q1 VETERINARY SCIENCES
Xiaolong Lu, Tiansong Zhan, Qiwen Zhou, Wenhao Yang, Kaituo Liu, Yu Chen, Ruyi Gao, Jiao Hu, Min Gu, Shunlin Hu, Xin-An Jiao, Xiaoquan Wang, Xiufan Liu, Xiaowen Liu
{"title":"绒源新城疫病毒的血凝素-神经氨酸酶蛋白通过 NF-κB 介导的程序性细胞死亡增强病毒感染。","authors":"Xiaolong Lu, Tiansong Zhan, Qiwen Zhou, Wenhao Yang, Kaituo Liu, Yu Chen, Ruyi Gao, Jiao Hu, Min Gu, Shunlin Hu, Xin-An Jiao, Xiaoquan Wang, Xiufan Liu, Xiaowen Liu","doi":"10.1186/s13567-024-01312-y","DOIUrl":null,"url":null,"abstract":"<p><p>The haemagglutinin-neuraminidase (HN) protein, a vital membrane glycoprotein, plays a pivotal role in the pathogenesis of Newcastle disease virus (NDV). Previously, we demonstrated that a mutation in the HN protein is essential for the enhanced virulence of JS/7/05/Ch, a velogenic variant NDV strain originating from the mesogenic vaccine strain Mukteswar. Here, we explored the effects of the HN protein during viral infection in vitro using three viruses: JS/7/05/Ch, Mukteswar, and an HN-replacement chimeric NDV, JS/MukHN. Through microscopic observation, CCK-8, and LDH release assays, we demonstrated that compared with Mukteswar and JS/MukHN, JS/7/05/Ch intensified the cellular damage and mortality attributed to the mutant HN protein. Furthermore, JS/7/05/Ch induced greater levels of apoptosis, as evidenced by the activation of caspase-3/8/9. Moreover, JS/7/05/Ch promoted autophagy, leading to increased autophagosome formation and autophagic flux. Subsequent pharmacological experiments revealed that inhibition of apoptosis and autophagy significantly impacted virus replication and cell viability in the JS/7/05/Ch-infected group, whereas less significant effects were observed in the other two infected groups. Notably, the mutant HN protein enhanced JS/7/05/Ch-induced apoptosis and autophagy by suppressing NF-κB activation, while it mitigated the effects of NF-κB on NDV infection. Overall, our study offers novel insights into the mechanisms underlying the increased virulence of NDV and serves as a reference for the development of vaccines.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"55 1","pages":"58"},"PeriodicalIF":3.7000,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077864/pdf/","citationCount":"0","resultStr":"{\"title\":\"The haemagglutinin-neuraminidase protein of velogenic Newcastle disease virus enhances viral infection through NF-κB-mediated programmed cell death.\",\"authors\":\"Xiaolong Lu, Tiansong Zhan, Qiwen Zhou, Wenhao Yang, Kaituo Liu, Yu Chen, Ruyi Gao, Jiao Hu, Min Gu, Shunlin Hu, Xin-An Jiao, Xiaoquan Wang, Xiufan Liu, Xiaowen Liu\",\"doi\":\"10.1186/s13567-024-01312-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The haemagglutinin-neuraminidase (HN) protein, a vital membrane glycoprotein, plays a pivotal role in the pathogenesis of Newcastle disease virus (NDV). Previously, we demonstrated that a mutation in the HN protein is essential for the enhanced virulence of JS/7/05/Ch, a velogenic variant NDV strain originating from the mesogenic vaccine strain Mukteswar. Here, we explored the effects of the HN protein during viral infection in vitro using three viruses: JS/7/05/Ch, Mukteswar, and an HN-replacement chimeric NDV, JS/MukHN. Through microscopic observation, CCK-8, and LDH release assays, we demonstrated that compared with Mukteswar and JS/MukHN, JS/7/05/Ch intensified the cellular damage and mortality attributed to the mutant HN protein. Furthermore, JS/7/05/Ch induced greater levels of apoptosis, as evidenced by the activation of caspase-3/8/9. Moreover, JS/7/05/Ch promoted autophagy, leading to increased autophagosome formation and autophagic flux. Subsequent pharmacological experiments revealed that inhibition of apoptosis and autophagy significantly impacted virus replication and cell viability in the JS/7/05/Ch-infected group, whereas less significant effects were observed in the other two infected groups. Notably, the mutant HN protein enhanced JS/7/05/Ch-induced apoptosis and autophagy by suppressing NF-κB activation, while it mitigated the effects of NF-κB on NDV infection. Overall, our study offers novel insights into the mechanisms underlying the increased virulence of NDV and serves as a reference for the development of vaccines.</p>\",\"PeriodicalId\":23658,\"journal\":{\"name\":\"Veterinary Research\",\"volume\":\"55 1\",\"pages\":\"58\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-05-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077864/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Veterinary Research\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.1186/s13567-024-01312-y\",\"RegionNum\":1,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"VETERINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Veterinary Research","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1186/s13567-024-01312-y","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
引用次数: 0

摘要

血凝素-神经氨酸酶(HN)蛋白是一种重要的膜糖蛋白,在新城疫病毒(NDV)的致病过程中起着关键作用。此前,我们曾证实,HN 蛋白的突变对 JS/7/05/Ch 的毒力增强至关重要,JS/7/05/Ch 是源自中源疫苗株 Mukteswar 的绒毛变异 NDV 株系。在此,我们使用三种病毒探讨了 HN 蛋白在体外病毒感染过程中的作用:JS/7/05/Ch、Mukteswar 和 HN 替代嵌合 NDV JS/MukHN。通过显微镜观察、CCK-8 和 LDH 释放测定,我们发现与 Mukteswar 和 JS/MukHN 相比,JS/7/05/Ch 加剧了突变 HN 蛋白对细胞的损伤和死亡率。此外,JS/7/05/Ch 还诱导了更高水平的细胞凋亡,Caspase-3/8/9 的激活就是证明。此外,JS/7/05/Ch 还促进自噬,导致自噬体形成和自噬通量增加。随后的药理实验显示,抑制细胞凋亡和自噬对 JS/7/05/Ch 感染组的病毒复制和细胞活力有显著影响,而对其他两个感染组的影响则不太明显。值得注意的是,突变型 HN 蛋白通过抑制 NF-κB 的活化增强了 JS/7/05/Ch 诱导的细胞凋亡和自噬,同时减轻了 NF-κB 对 NDV 感染的影响。总之,我们的研究为了解 NDV 毒力增强的机制提供了新的视角,并为疫苗的开发提供了参考。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The haemagglutinin-neuraminidase protein of velogenic Newcastle disease virus enhances viral infection through NF-κB-mediated programmed cell death.

The haemagglutinin-neuraminidase (HN) protein, a vital membrane glycoprotein, plays a pivotal role in the pathogenesis of Newcastle disease virus (NDV). Previously, we demonstrated that a mutation in the HN protein is essential for the enhanced virulence of JS/7/05/Ch, a velogenic variant NDV strain originating from the mesogenic vaccine strain Mukteswar. Here, we explored the effects of the HN protein during viral infection in vitro using three viruses: JS/7/05/Ch, Mukteswar, and an HN-replacement chimeric NDV, JS/MukHN. Through microscopic observation, CCK-8, and LDH release assays, we demonstrated that compared with Mukteswar and JS/MukHN, JS/7/05/Ch intensified the cellular damage and mortality attributed to the mutant HN protein. Furthermore, JS/7/05/Ch induced greater levels of apoptosis, as evidenced by the activation of caspase-3/8/9. Moreover, JS/7/05/Ch promoted autophagy, leading to increased autophagosome formation and autophagic flux. Subsequent pharmacological experiments revealed that inhibition of apoptosis and autophagy significantly impacted virus replication and cell viability in the JS/7/05/Ch-infected group, whereas less significant effects were observed in the other two infected groups. Notably, the mutant HN protein enhanced JS/7/05/Ch-induced apoptosis and autophagy by suppressing NF-κB activation, while it mitigated the effects of NF-κB on NDV infection. Overall, our study offers novel insights into the mechanisms underlying the increased virulence of NDV and serves as a reference for the development of vaccines.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信