非洲猪瘟病毒 E120R 可抑制 cGAS-STING 介导的 IFN-β 和 NF-κB 通路

Shuai Cui, Yang Wang, Shiyu Chen, Lichun Fang, Yajun Jiang, Zhongbao Pang, Yitong Jiang, Xiaoyu Guo, Hongfei Zhu, Hong Jia
{"title":"非洲猪瘟病毒 E120R 可抑制 cGAS-STING 介导的 IFN-β 和 NF-κB 通路","authors":"Shuai Cui,&nbsp;Yang Wang,&nbsp;Shiyu Chen,&nbsp;Lichun Fang,&nbsp;Yajun Jiang,&nbsp;Zhongbao Pang,&nbsp;Yitong Jiang,&nbsp;Xiaoyu Guo,&nbsp;Hongfei Zhu,&nbsp;Hong Jia","doi":"10.1002/aro2.38","DOIUrl":null,"url":null,"abstract":"<p>African swine fever (ASF) is an acute and severe contagious disease triggered by the African swine fever virus (ASFV), which severely threatens the global swine industry. At present, no safe and efficacious vaccine has been provided to prevent and control this disease. The pathogenesis and immune evasion mechanism of ASFV are still unknown, which seriously hinders the development of safe and effective ASF vaccines. Certain proteins of ASFV involved in immunosuppression helped to evade the host innate immune response. The cGAS-STING signaling pathway is important to the innate immune system. It induces the production of type I interferons (IFNs) and other cytokines by recognizing cytoplasmic DNA, mediating antimicrobial innate immunity through type I IFN, and nuclear factor-κB (NF-κB) pathways. In the present study, E120R, a late-phase expression protein and a key virulent factor of ASFV inhibited cGAS-STING mediated promoter activities of IFN-β and NF-κB in HEK293T cells. The ectopic expression of E120R down-regulated IFN-β pathway by targeting interferon regulatory factor 3 (IRF3) and p65, inhibited the phosphorylation of STING, and further inhibited the phosphorylation of TANK-binding kinase 1 (TBK1) and IRF3, with no significant effects on p65 phosphorylation. Additionally, E120R also inhibited the NF-κB pathways by inhibiting the nuclear translocation of p50 and p65, which was mediated by Sendai virus (SeV). Further, the study showed that the 61–80 amino acids sites in the C-terminal domain of E120R were crucial for these functions. In conclusion, our work preliminarily elucidated a novel mechanism of inhibiting host innate immune response by ASFV E120R, which will provide a new target for the ASFV live gene deletion vaccine development and the theoretical basis for ASFV prevention.</p>","PeriodicalId":100086,"journal":{"name":"Animal Research and One Health","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aro2.38","citationCount":"0","resultStr":"{\"title\":\"African swine fever virus E120R inhibited cGAS-STING-mediated IFN-β and NF-κB pathways\",\"authors\":\"Shuai Cui,&nbsp;Yang Wang,&nbsp;Shiyu Chen,&nbsp;Lichun Fang,&nbsp;Yajun Jiang,&nbsp;Zhongbao Pang,&nbsp;Yitong Jiang,&nbsp;Xiaoyu Guo,&nbsp;Hongfei Zhu,&nbsp;Hong Jia\",\"doi\":\"10.1002/aro2.38\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>African swine fever (ASF) is an acute and severe contagious disease triggered by the African swine fever virus (ASFV), which severely threatens the global swine industry. At present, no safe and efficacious vaccine has been provided to prevent and control this disease. The pathogenesis and immune evasion mechanism of ASFV are still unknown, which seriously hinders the development of safe and effective ASF vaccines. Certain proteins of ASFV involved in immunosuppression helped to evade the host innate immune response. The cGAS-STING signaling pathway is important to the innate immune system. It induces the production of type I interferons (IFNs) and other cytokines by recognizing cytoplasmic DNA, mediating antimicrobial innate immunity through type I IFN, and nuclear factor-κB (NF-κB) pathways. In the present study, E120R, a late-phase expression protein and a key virulent factor of ASFV inhibited cGAS-STING mediated promoter activities of IFN-β and NF-κB in HEK293T cells. The ectopic expression of E120R down-regulated IFN-β pathway by targeting interferon regulatory factor 3 (IRF3) and p65, inhibited the phosphorylation of STING, and further inhibited the phosphorylation of TANK-binding kinase 1 (TBK1) and IRF3, with no significant effects on p65 phosphorylation. Additionally, E120R also inhibited the NF-κB pathways by inhibiting the nuclear translocation of p50 and p65, which was mediated by Sendai virus (SeV). Further, the study showed that the 61–80 amino acids sites in the C-terminal domain of E120R were crucial for these functions. In conclusion, our work preliminarily elucidated a novel mechanism of inhibiting host innate immune response by ASFV E120R, which will provide a new target for the ASFV live gene deletion vaccine development and the theoretical basis for ASFV prevention.</p>\",\"PeriodicalId\":100086,\"journal\":{\"name\":\"Animal Research and One Health\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-12-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aro2.38\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Animal Research and One Health\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/aro2.38\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Animal Research and One Health","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/aro2.38","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

非洲猪瘟(African swine fever, ASF)是由非洲猪瘟病毒(African swine fever virus, ASFV)引发的一种急性重症传染病,严重威胁着全球养猪业。目前,还没有安全有效的疫苗来预防和控制这种疾病。非洲猪瘟的发病机制和免疫逃避机制尚不清楚,严重阻碍了安全有效的非洲猪瘟疫苗的研制。ASFV的某些蛋白参与免疫抑制,帮助逃避宿主先天免疫反应。cGAS - STING信号通路对先天免疫系统非常重要。它通过识别细胞质DNA诱导I型干扰素(IFN)和其他细胞因子的产生,通过I型IFN和核因子κB (NF - κB)途径介导抗菌先天免疫。在本研究中,ASFV的晚期表达蛋白E120R和关键毒力因子抑制了cGAS - STING介导的HEK293T细胞中IFN - β和NF - κB启动子活性。E120R的异位表达通过靶向干扰素调节因子3 (IRF3)和p65下调IFN - β通路,抑制STING的磷酸化,并进一步抑制TANK结合激酶1 (TBK1)和IRF3的磷酸化,但对p65的磷酸化无显著影响。此外,E120R还通过抑制仙台病毒(SeV)介导的p50和p65的核易位来抑制NF‐κB通路。此外,研究表明,E120R C末端区域的61-80个氨基酸位点对这些功能至关重要。总之,我们的工作初步阐明了ASFV E120R抑制宿主先天免疫反应的新机制,将为ASFV基因缺失活疫苗的研制提供新的靶点,并为ASFV的预防提供理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
African swine fever virus E120R inhibited cGAS-STING-mediated IFN-β and NF-κB pathways

African swine fever (ASF) is an acute and severe contagious disease triggered by the African swine fever virus (ASFV), which severely threatens the global swine industry. At present, no safe and efficacious vaccine has been provided to prevent and control this disease. The pathogenesis and immune evasion mechanism of ASFV are still unknown, which seriously hinders the development of safe and effective ASF vaccines. Certain proteins of ASFV involved in immunosuppression helped to evade the host innate immune response. The cGAS-STING signaling pathway is important to the innate immune system. It induces the production of type I interferons (IFNs) and other cytokines by recognizing cytoplasmic DNA, mediating antimicrobial innate immunity through type I IFN, and nuclear factor-κB (NF-κB) pathways. In the present study, E120R, a late-phase expression protein and a key virulent factor of ASFV inhibited cGAS-STING mediated promoter activities of IFN-β and NF-κB in HEK293T cells. The ectopic expression of E120R down-regulated IFN-β pathway by targeting interferon regulatory factor 3 (IRF3) and p65, inhibited the phosphorylation of STING, and further inhibited the phosphorylation of TANK-binding kinase 1 (TBK1) and IRF3, with no significant effects on p65 phosphorylation. Additionally, E120R also inhibited the NF-κB pathways by inhibiting the nuclear translocation of p50 and p65, which was mediated by Sendai virus (SeV). Further, the study showed that the 61–80 amino acids sites in the C-terminal domain of E120R were crucial for these functions. In conclusion, our work preliminarily elucidated a novel mechanism of inhibiting host innate immune response by ASFV E120R, which will provide a new target for the ASFV live gene deletion vaccine development and the theoretical basis for ASFV prevention.

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
自引率
0.00%
发文量
0
期刊最新文献
Issue Information Temperature and humidity as drivers for the transmission of zoonotic diseases Free iron accumulation and oxidative stress burden induce ferroptotic atrophy of chicken yolk sac during the late embryogenesis Selection of the most informative wavenumbers to improve prediction accuracy of milk fatty acid profile based on milk mid‐infrared spectra data Functional roles of folic acid in alleviating dexamethasone‐induced fatty liver syndrome in laying hens
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1