• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

黄病毒prM蛋白与MDA5和MAVS相互作用以抑制RLR抗病毒信号传导。

Flavivirus prM interacts with MDA5 and MAVS to inhibit RLR antiviral signaling.

作者信息

Sui Liyan, Zhao Yinghua, Wang Wenfang, Chi Hongmiao, Tian Tian, Wu Ping, Zhang Jinlong, Zhao Yicheng, Wei Zheng-Kai, Hou Zhijun, Zhou Guoqiang, Wang Guoqing, Wang Zedong, Liu Quan

机构信息

Department of Infectious Diseases and Center of Infectious diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Key Laboratory of Zoonotic Diseases, The First Hospital of Jilin University, Changchun, China.

College of Basic Medical Science, Jilin University, Changchun, China.

出版信息

Cell Biosci. 2023 Jan 13;13(1):9. doi: 10.1186/s13578-023-00957-0.

DOI:10.1186/s13578-023-00957-0
PMID:36639652
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9837762/
Abstract

BACKGROUND

Vector-borne flaviviruses, including tick-borne encephalitis virus (TBEV), Zika virus (ZIKV), West Nile virus (WNV), yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), pose a growing threat to public health worldwide, and have evolved complex mechanisms to overcome host antiviral innate immunity. However, the underlying mechanisms of flavivirus structural proteins to evade host immune response remain elusive.

RESULTS

We showed that TBEV structural protein, pre-membrane (prM) protein, could inhibit type I interferon (IFN-I) production. Mechanically, TBEV prM interacted with both MDA5 and MAVS and interfered with the formation of MDA5-MAVS complex, thereby impeding the nuclear translocation and dimerization of IRF3 to inhibit RLR antiviral signaling. ZIKV and WNV prM was also demonstrated to interact with both MDA5 and MAVS, while dengue virus serotype 2 (DENV2) and YFV prM associated only with MDA5 or MAVS to suppress IFN-I production. In contrast, JEV prM could not suppress IFN-I production. Overexpression of TBEV and ZIKV prM significantly promoted the replication of TBEV and Sendai virus.

CONCLUSION

Our findings reveal the immune evasion mechanisms of flavivirus prM, which may contribute to understanding flavivirus pathogenicity, therapeutic intervention and vaccine development.

摘要

背景

包括蜱传脑炎病毒（TBEV）、寨卡病毒（ZIKV）、西尼罗河病毒（WNV）、黄热病毒（YFV）、登革病毒（DENV）和日本脑炎病毒（JEV）在内的媒介传播黄病毒，对全球公共卫生构成了日益严重的威胁，并已进化出复杂的机制来克服宿主抗病毒先天免疫。然而，黄病毒结构蛋白逃避宿主免疫反应的潜在机制仍不清楚。

结果

我们发现TBEV结构蛋白，即前膜（prM）蛋白，可抑制I型干扰素（IFN-I）的产生。机制上，TBEV prM与MDA5和MAVS均相互作用，并干扰MDA5-MAVS复合物的形成，从而阻碍IRF3的核转位和二聚化，以抑制RLR抗病毒信号传导。寨卡病毒和西尼罗河病毒的prM也被证明与MDA5和MAVS均相互作用，而登革病毒2型（DENV2）和黄热病毒的prM仅与MDA5或MAVS相关联以抑制IFN-I的产生。相比之下，日本脑炎病毒的prM不能抑制IFN-I的产生。过表达TBEV和寨卡病毒的prM显著促进了TBEV和仙台病毒的复制。

结论

我们的研究结果揭示了黄病毒prM的免疫逃逸机制，这可能有助于理解黄病毒的致病性、治疗干预和疫苗开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/958d0d9c2919/13578_2023_957_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/45c691063c31/13578_2023_957_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/f29087188a34/13578_2023_957_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/eb1988368bd1/13578_2023_957_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/da1dc7b18e94/13578_2023_957_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/67a9793552ac/13578_2023_957_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/f82e1931c53d/13578_2023_957_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/958d0d9c2919/13578_2023_957_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/45c691063c31/13578_2023_957_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/f29087188a34/13578_2023_957_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/eb1988368bd1/13578_2023_957_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/da1dc7b18e94/13578_2023_957_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/67a9793552ac/13578_2023_957_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/f82e1931c53d/13578_2023_957_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c11/9837957/958d0d9c2919/13578_2023_957_Fig7_HTML.jpg

相似文献

1
Flavivirus prM interacts with MDA5 and MAVS to inhibit RLR antiviral signaling.黄病毒prM蛋白与MDA5和MAVS相互作用以抑制RLR抗病毒信号传导。
Cell Biosci. 2023 Jan 13;13(1):9. doi: 10.1186/s13578-023-00957-0.
2
West Nile Virus NS1 Antagonizes Interferon Beta Production by Targeting RIG-I and MDA5.西尼罗河病毒NS1通过靶向维甲酸诱导基因I（RIG-I）和黑色素瘤分化相关基因5（MDA5）来拮抗β干扰素的产生。
J Virol. 2017 Aug 24;91(18). doi: 10.1128/JVI.02396-16. Print 2017 Sep 15.
3
STAT5: a Target of Antagonism by Neurotropic Flaviviruses.STAT5：神经亲和性黄病毒的拮抗靶标。
J Virol. 2019 Nov 13;93(23). doi: 10.1128/JVI.00665-19. Print 2019 Dec 1.
4
Viperin Restricts Zika Virus and Tick-Borne Encephalitis Virus Replication by Targeting NS3 for Proteasomal Degradation.蝰蛇毒素通过靶向NS3进行蛋白酶体降解来限制寨卡病毒和蜱传脑炎病毒的复制。
J Virol. 2018 Mar 14;92(7). doi: 10.1128/JVI.02054-17. Print 2018 Apr 1.
5
The Flavivirus Non-Structural Protein 5 (NS5): Structure, Functions, and Targeting for Development of Vaccines and Therapeutics.黄病毒非结构蛋白5（NS5）：结构、功能以及疫苗和治疗药物研发的靶点
Vaccines (Basel). 2024 Aug 1;12(8):865. doi: 10.3390/vaccines12080865.
6
Zika Virus Non-structural Protein 4A Blocks the RLR-MAVS Signaling.寨卡病毒非结构蛋白4A阻断RLR-MAVS信号通路。
Front Microbiol. 2018 Jun 25;9:1350. doi: 10.3389/fmicb.2018.01350. eCollection 2018.
7
A MicroRNA Screen Identifies the Wnt Signaling Pathway as a Regulator of the Interferon Response during Flavivirus Infection.一项微小RNA筛选确定Wnt信号通路是黄病毒感染期间干扰素反应的调节因子。
J Virol. 2017 Mar 29;91(8). doi: 10.1128/JVI.02388-16. Print 2017 Apr 15.
8
Glycyrrhizic Acid Derivatives Bearing Amino Acid Residues in the Carbohydrate Part as Dengue Virus E Protein Inhibitors: Synthesis and Antiviral Activity.糖基部分带有氨基酸残基的甘草次酸衍生物作为登革病毒 E 蛋白抑制剂：合成与抗病毒活性。
Int J Mol Sci. 2022 Sep 7;23(18):10309. doi: 10.3390/ijms231810309.
9
Memory T Cells in Flavivirus Vaccination.黄病毒疫苗接种中的记忆T细胞。
Vaccines (Basel). 2018 Oct 18;6(4):73. doi: 10.3390/vaccines6040073.
10
Immune evasion strategies of flaviviruses.黄病毒的免疫逃逸策略。
Vaccine. 2013 Jan 7;31(3):461-71. doi: 10.1016/j.vaccine.2012.11.015. Epub 2012 Nov 13.

引用本文的文献

1
Neurovirulence of Zika virus-encoded proteins.寨卡病毒编码蛋白的神经毒性。
Arch Virol. 2025 Jun 7;170(7):150. doi: 10.1007/s00705-025-06338-x.
2
Exploiting host kinases to combat dengue virus infection and disease.利用宿主激酶对抗登革病毒感染及疾病。
Antiviral Res. 2025 May 8;241:106172. doi: 10.1016/j.antiviral.2025.106172.
3
ZIKV prM hijacks PIM1 kinase for phosphorylation to prevent ubiquitin-mediated degradation and facilitate viral replication.寨卡病毒（ZIKV）的prM劫持PIM1激酶进行磷酸化，以防止泛素介导的降解并促进病毒复制。

本文引用的文献

1
Leu-to-Phe substitution at prM decreases the growth ability of Zika virus and partially reduces its pathogenicity in mice.在 prM 处亮氨酸到苯丙氨酸的取代降低了寨卡病毒的生长能力，并部分降低了其在小鼠中的致病性。
Sci Rep. 2021 Oct 4;11(1):19635. doi: 10.1038/s41598-021-99086-2.
2
Inhibition of MAVS Aggregation-Mediated Type-I Interferon Signaling by Foot-and-Mouth Disease Virus VP3.口蹄疫病毒 VP3 通过抑制 MAVS 聚集介导的 I 型干扰素信号通路
Viruses. 2021 Sep 6;13(9):1776. doi: 10.3390/v13091776.
3
The molecular mechanism of RIG-I activation and signaling.
Front Cell Infect Microbiol. 2024 Nov 29;14:1502770. doi: 10.3389/fcimb.2024.1502770. eCollection 2024.
4
Multi-protomics analysis identified host cellular pathways perturbed by tick-borne encephalitis virus infection.多组学分析鉴定了蜱传脑炎病毒感染干扰的宿主细胞途径。
Nat Commun. 2024 Nov 30;15(1):10435. doi: 10.1038/s41467-024-54628-w.
5
MAVS signaling shapes microglia responses to neurotropic virus infection.MAVS 信号通路调控小胶质细胞对神经亲和性病毒感染的反应。
J Neuroinflammation. 2024 Oct 18;21(1):264. doi: 10.1186/s12974-024-03258-6.
6
Fitness adaptations of Japanese encephalitis virus in pigs following vector-free serial passaging.猪体中日本脑炎病毒在无媒介连续传代后的适应性变化。
PLoS Pathog. 2024 Aug 26;20(8):e1012059. doi: 10.1371/journal.ppat.1012059. eCollection 2024 Aug.
7
N6-methyladenosine modification positively regulate Japanese encephalitis virus replication.N6-甲基腺苷修饰正向调控日本脑炎病毒复制。
Virol J. 2024 Jan 19;21(1):23. doi: 10.1186/s12985-023-02275-w.
8
A review on Zika vaccine development.寨卡病毒疫苗的开发研究综述。
Pathog Dis. 2024 Feb 7;82. doi: 10.1093/femspd/ftad036.
9
Mosquito-borne flaviviruses and type I interferon: catch me if you can!蚊媒黄病毒与I型干扰素：看你能否抓住我！
Front Microbiol. 2023 Oct 30;14:1257024. doi: 10.3389/fmicb.2023.1257024. eCollection 2023.
RIG-I 的激活和信号转导的分子机制。
Immunol Rev. 2021 Nov;304(1):154-168. doi: 10.1111/imr.13022. Epub 2021 Sep 12.
4
A dual-role of SARS-CoV-2 nucleocapsid protein in regulating innate immune response.SARS-CoV-2 核衣壳蛋白在调节固有免疫反应中的双重作用。
Signal Transduct Target Ther. 2021 Sep 1;6(1):331. doi: 10.1038/s41392-021-00742-w.
5
Molecular detection and phylogenetic analysis of tick-borne encephalitis virus in ticks in northeastern China.东北地区蜱传脑炎病毒在蜱中的分子检测与系统进化分析。
J Med Virol. 2022 Feb;94(2):507-513. doi: 10.1002/jmv.27303. Epub 2021 Sep 8.
6
SARS-CoV-2 Membrane Protein Inhibits Type I Interferon Production Through Ubiquitin-Mediated Degradation of TBK1.SARS-CoV-2 膜蛋白通过泛素介导的 TBK1 降解抑制 I 型干扰素的产生。
Front Immunol. 2021 May 18;12:662989. doi: 10.3389/fimmu.2021.662989. eCollection 2021.
7
Structure-guided paradigm shifts in flavivirus assembly and maturation mechanisms.结构导向的黄病毒组装和成熟机制的范式转变。
Adv Virus Res. 2020;108:33-83. doi: 10.1016/bs.aivir.2020.08.003. Epub 2020 Sep 23.
8
The VP3 Protein of Bluetongue Virus Associates with the MAVS Complex and Interferes with the RIG-I-Signaling Pathway.蓝舌病毒 VP3 蛋白与 MAVS 复合物结合并干扰 RIG-I 信号通路。
Viruses. 2021 Feb 2;13(2):230. doi: 10.3390/v13020230.
9
Regulation of RIG-I-like receptor-mediated signaling: interaction between host and viral factors.RIG-I 样受体介导的信号转导调控：宿主与病毒因子的相互作用。
Cell Mol Immunol. 2021 Mar;18(3):539-555. doi: 10.1038/s41423-020-00602-7. Epub 2021 Jan 18.
10
DENV-3 precursor membrane (prM) glycoprotein enhances E protein immunogenicity and confers protection against DENV-2 infections in a murine model.登革病毒3型前体膜（prM）糖蛋白增强E蛋白免疫原性，并在小鼠模型中赋予针对登革病毒2型感染的保护作用。
Hum Vaccin Immunother. 2021 May 4;17(5):1271-1277. doi: 10.1080/21645515.2020.1826798. Epub 2020 Oct 29.