Tribbles pseudokinase 3 promotes enterovirus A71 infection via dual mechanisms.

IF 8.4 2区 医学 Q1 IMMUNOLOGY Emerging Microbes & Infections Pub Date : 2024-12-01 Epub Date: 2024-01-30 DOI:10.1080/22221751.2024.2307514
Huiqiang Wang, Ke Li, Boming Cui, Haiyan Yan, Shuo Wu, Kun Wang, Ge Yang, Jiandong Jiang, Yuhuan Li
{"title":"Tribbles pseudokinase 3 promotes enterovirus A71 infection via dual mechanisms.","authors":"Huiqiang Wang, Ke Li, Boming Cui, Haiyan Yan, Shuo Wu, Kun Wang, Ge Yang, Jiandong Jiang, Yuhuan Li","doi":"10.1080/22221751.2024.2307514","DOIUrl":null,"url":null,"abstract":"<p><p>Enterovirus A71 (EV-A71) is the main pathogen causing hand, foot and mouth disease (HFMD) in children and occasionally associated with neurological diseases such as aseptic meningitis, brainstem encephalitis (BE) and acute flaccid paralysis. We report here that cellular pseudokinase tribbles 3 (TRIB3) facilitates the infection of EV-A71 via dual mechanisms. In one hand, TRIB3 maintains the metabolic stability of scavenger receptor class B member 2 (SCARB2), the <i>bona fide</i> receptor of EV-A71, to enhance the infectious entry and spreading of the virus. On the other hand, TRIB3 facilitates the replication of EV-A71 RNA in a SCARB2-independent manner. The critical role of TRIB3 in EV-A71 infection and pathogenesis was further demonstrated <i>in vivo</i> in mice. In comparison to wild-type C57BL/6 mice, EV-A71 infection in TRIB3 knockdown mice (<i>Trib3</i><sup>+/-</sup>) resulted in significantly lower viral loads in muscular tissues and reduced lethality and severity of clinical scores and tissue pathology. In addition, TRIB3 also promoted the replication of coxsackievirus B3 (CVB3) and coxsackievirus A16 (CVA16) <i>in vitro</i>. In conclusion, our results suggest that TRIB3 is one of key host cellular proteins required for the infection and pathogenesis of EV-A71 and some other human enteroviruses and may thus be a potential therapeutic target for combating the infection of those viruses.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":8.4000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10829831/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Emerging Microbes & Infections","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/22221751.2024.2307514","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Enterovirus A71 (EV-A71) is the main pathogen causing hand, foot and mouth disease (HFMD) in children and occasionally associated with neurological diseases such as aseptic meningitis, brainstem encephalitis (BE) and acute flaccid paralysis. We report here that cellular pseudokinase tribbles 3 (TRIB3) facilitates the infection of EV-A71 via dual mechanisms. In one hand, TRIB3 maintains the metabolic stability of scavenger receptor class B member 2 (SCARB2), the bona fide receptor of EV-A71, to enhance the infectious entry and spreading of the virus. On the other hand, TRIB3 facilitates the replication of EV-A71 RNA in a SCARB2-independent manner. The critical role of TRIB3 in EV-A71 infection and pathogenesis was further demonstrated in vivo in mice. In comparison to wild-type C57BL/6 mice, EV-A71 infection in TRIB3 knockdown mice (Trib3+/-) resulted in significantly lower viral loads in muscular tissues and reduced lethality and severity of clinical scores and tissue pathology. In addition, TRIB3 also promoted the replication of coxsackievirus B3 (CVB3) and coxsackievirus A16 (CVA16) in vitro. In conclusion, our results suggest that TRIB3 is one of key host cellular proteins required for the infection and pathogenesis of EV-A71 and some other human enteroviruses and may thus be a potential therapeutic target for combating the infection of those viruses.

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
Tribbles 伪激酶 3 通过双重机制促进肠病毒 A71 感染。
肠道病毒 A71(EV-A71)是导致儿童手足口病(HFMD)的主要病原体,偶尔也与无菌性脑膜炎、脑干脑炎(BE)和急性弛缓性麻痹等神经系统疾病有关。我们在此报告,细胞伪激酶tribbles 3(TRIB3)通过双重机制促进了EV-A71的感染。一方面,TRIB3能维持EV-A71的真正受体--清道夫受体B类成员2(SCARB2)的代谢稳定性,从而增强病毒的感染性进入和传播。另一方面,TRIB3 以一种与 SCARB2 无关的方式促进 EV-A71 RNA 的复制。TRIB3 在 EV-A71 感染和致病过程中的关键作用在小鼠体内得到了进一步证实。与野生型C57BL/6小鼠相比,TRIB3基因敲除小鼠(Trib3+/-)感染EV-A71后,肌肉组织中的病毒载量明显降低,致死率降低,临床评分和组织病理学的严重程度也有所减轻。此外,TRIB3 还能促进柯萨奇病毒 B3(CVB3)和柯萨奇病毒 A16(CVA16)在体外的复制。总之,我们的研究结果表明,TRIB3是EV-A71和其他一些人类肠道病毒感染和致病所需的关键宿主细胞蛋白之一,因此可能是抗击这些病毒感染的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Emerging Microbes & Infections
Emerging Microbes & Infections IMMUNOLOGY-MICROBIOLOGY
CiteScore
26.20
自引率
2.30%
发文量
276
审稿时长
20 weeks
期刊介绍: Emerging Microbes & Infections is a peer-reviewed, open-access journal dedicated to publishing research at the intersection of emerging immunology and microbiology viruses. The journal's mission is to share information on microbes and infections, particularly those gaining significance in both biological and clinical realms due to increased pathogenic frequency. Emerging Microbes & Infections is committed to bridging the scientific gap between developed and developing countries. This journal addresses topics of critical biological and clinical importance, including but not limited to: - Epidemic surveillance - Clinical manifestations - Diagnosis and management - Cellular and molecular pathogenesis - Innate and acquired immune responses between emerging microbes and their hosts - Drug discovery - Vaccine development research Emerging Microbes & Infections invites submissions of original research articles, review articles, letters, and commentaries, fostering a platform for the dissemination of impactful research in the field.
期刊最新文献
Experimental co-infection of calves with SARS-CoV-2 Delta and Omicron variants of concern. Safety and immunogenicity of heterologous boosting with orally administered aerosolized bivalent adenovirus type-5 vectored COVID-19 vaccine and B.1.1.529 variant adenovirus type-5 vectored COVID-19 vaccine in adults 18 years and older: a randomized, double blinded, parallel controlled trial. Evolution and biological characterization of H5N1 influenza viruses bearing the clade 2.3.2.1 hemagglutinin gene. Recombinant duck enteritis virus bearing the hemagglutinin genes of H5 and H7 influenza viruses is an ideal multivalent live vaccine in ducks. Human monoclonal antibody F61 nasal spray effectively protected high-risk populations from SARS-CoV-2 variants during the COVID-19 pandemic from late 2022 to early 2023 in China.
×
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