Golgi-derived extracellular vesicle production induced by SARS-CoV-2 envelope protein.

IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Apoptosis Pub Date : 2024-11-23 DOI:10.1007/s10495-024-02035-3
Qiguang Li, Qian Liu, Shuangqu Li, Xiaoli Zuo, Hu Zhou, Zhaobing Gao, Bingqing Xia
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Abstract

Extracellular vesicles facilitate cell-to-cell communication, and some enveloped viruses utilize these vesicles as carriers to mediate viral transmission. SARS-CoV-2 envelope protein (2-E) forms a cation channel and overexpression of 2-E led to the generation of a distinct type of large extracellular vesicles (2-E-EVs). Although 2-E-EVs have been demonstrated to facilitate viral transmission in a receptor-independent way, the characteristics and biogenesis mechanism remain enigmatic. Via lipidomics and proteomic analysis, we found 2-E-EVs are distinct from endosome-derived exosomes. 2-E-EVs are notably enriched in Golgi apparatus components, aligning with the observed fragmentation in Golgi morphology. Through live cell imaging, we established a connection between 2-E-EVs formation, Golgi fragmentation, and channel activity, emphasizing the role of 2-E-EVs as ion channel-induced extracellular vesicles. Our work highlights 2-E-EVs as distinctive Golgi-derived vesicles, contributing to a deeper understanding of 2-E channel-mediated virus-host dynamics, with implications for therapeutic strategies and drug delivery.

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SARS-CoV-2包膜蛋白诱导的细胞外囊泡生成。
细胞外囊泡有助于细胞间的交流,一些包膜病毒利用这些囊泡作为载体介导病毒传播。SARS-CoV-2 包膜蛋白(2-E)形成了一个阳离子通道,过量表达 2-E 导致产生了一种独特的大细胞外囊泡(2-EVs)。虽然 2-EVs 已被证明能以一种与受体无关的方式促进病毒传播,但其特征和生物生成机制仍然是个谜。通过脂质组学和蛋白质组学分析,我们发现2-EVs有别于内泌体衍生的外泌体。2-EV明显富含高尔基体成分,这与观察到的高尔基体形态破碎一致。通过活细胞成像,我们建立了2-E-EVs形成、高尔基体破碎和通道活性之间的联系,强调了2-E-EVs作为离子通道诱导的细胞外囊泡的作用。我们的研究突出了 2-EVs 作为独特的高尔基体衍生囊泡的作用,有助于加深对 2-E 通道介导的病毒-宿主动力学的理解,并对治疗策略和药物递送产生影响。
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来源期刊
Apoptosis
Apoptosis 生物-生化与分子生物学
CiteScore
9.10
自引率
4.20%
发文量
85
审稿时长
1 months
期刊介绍: Apoptosis, a monthly international peer-reviewed journal, focuses on the rapid publication of innovative investigations into programmed cell death. The journal aims to stimulate research on the mechanisms and role of apoptosis in various human diseases, such as cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis, and aging. The Editor-In-Chief acknowledges the importance of advancing clinical therapies for apoptosis-related diseases. Apoptosis considers Original Articles, Reviews, Short Communications, Letters to the Editor, and Book Reviews for publication.
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