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
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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.

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。
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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.
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