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严重急性呼吸综合征冠状病毒2型重塑高尔基体以促进病毒组装和分泌。

SARS-CoV-2 remodels the Golgi apparatus to facilitate viral assembly and secretion.

作者信息

Zhang Jianchao, Kennedy Andrew, de Melo Jorge Daniel Macedo, Xing Lijuan, Reid Whitney, Bui Sarah, Joppich Joseph, Rose Molly, Ercan Sevval, Tang Qiyi, Tai Andrew W, Wang Yanzhuang

机构信息

Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.

Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

出版信息

bioRxiv. 2024 Mar 15:2022.03.04.483074. doi: 10.1101/2022.03.04.483074.

DOI:10.1101/2022.03.04.483074
PMID:35291301
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8923104/
Abstract

The COVID-19 pandemic is caused by SARS-CoV-2, an enveloped RNA virus. Despite extensive investigation, the molecular mechanisms for its assembly and secretion remain largely elusive. Here, we show that SARS-CoV-2 infection induces global alterations of the host endomembrane system, including dramatic Golgi fragmentation. SARS-CoV-2 virions are enriched in the fragmented Golgi. Disrupting Golgi function with small molecules strongly inhibits viral infection. Significantly, SARS-CoV-2 infection down-regulates GRASP55 but up-regulates TGN46 protein levels. Surprisingly, GRASP55 expression reduces both viral secretion and spike number on each virion, while GRASP55 depletion displays opposite effects. In contrast, TGN46 depletion only inhibits viral secretion without affecting spike incorporation into virions. TGN46 depletion and GRASP55 expression additively inhibit viral secretion, indicating that they act at different stages. Taken together, we show that SARS-CoV-2 alters Golgi structure and function to control viral assembly and secretion, highlighting the Golgi as a potential therapeutic target for blocking SARS-CoV-2 infection.

摘要

新冠疫情由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起，这是一种有包膜的RNA病毒。尽管进行了广泛研究，但其组装和分泌的分子机制仍 largely难以捉摸。在此，我们表明SARS-CoV-2感染会引起宿主内膜系统的全局改变，包括高尔基体的显著碎片化。SARS-CoV-2病毒粒子在碎片化的高尔基体中富集。用小分子破坏高尔基体功能会强烈抑制病毒感染。值得注意的是，SARS-CoV-2感染会下调GRASP55，但上调TGN46蛋白水平。令人惊讶的是，GRASP55的表达会降低病毒分泌以及每个病毒粒子上的刺突数量，而GRASP55的缺失则显示出相反的效果。相比之下，TGN46的缺失仅抑制病毒分泌，而不影响刺突掺入病毒粒子。TGN46的缺失和GRASP55的表达对病毒分泌有累加抑制作用，表明它们作用于不同阶段。综上所述，我们表明SARS-CoV-2会改变高尔基体的结构和功能以控制病毒的组装和分泌，突出了高尔基体作为阻断SARS-CoV-2感染的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/97db30a93ed3/nihpp-2022.03.04.483074v3-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/13cb4977ebfc/nihpp-2022.03.04.483074v3-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/609f6ecd8645/nihpp-2022.03.04.483074v3-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/95d583dd62e1/nihpp-2022.03.04.483074v3-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/4814e7a19397/nihpp-2022.03.04.483074v3-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/529390b3781e/nihpp-2022.03.04.483074v3-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/d9382da8f248/nihpp-2022.03.04.483074v3-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/497772a5c652/nihpp-2022.03.04.483074v3-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/97db30a93ed3/nihpp-2022.03.04.483074v3-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/13cb4977ebfc/nihpp-2022.03.04.483074v3-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/609f6ecd8645/nihpp-2022.03.04.483074v3-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/95d583dd62e1/nihpp-2022.03.04.483074v3-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/4814e7a19397/nihpp-2022.03.04.483074v3-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/529390b3781e/nihpp-2022.03.04.483074v3-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/d9382da8f248/nihpp-2022.03.04.483074v3-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/497772a5c652/nihpp-2022.03.04.483074v3-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a97b/10945641/97db30a93ed3/nihpp-2022.03.04.483074v3-f0008.jpg

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本文引用的文献

1
Sorting of secretory proteins at the -Golgi network by human TGN46.人TGN46在高尔基体网络中对分泌蛋白的分选
Elife. 2024 Mar 11;12:RP91708. doi: 10.7554/eLife.91708.
2
Membrane remodeling and trafficking piloted by SARS-CoV-2.由 SARS-CoV-2 驱动的膜重塑和运输。
Trends Cell Biol. 2024 Sep;34(9):785-800. doi: 10.1016/j.tcb.2023.12.006. Epub 2024 Jan 22.
3
GRASP55 regulates the unconventional secretion and aggregation of mutant huntingtin.GRASP55 调控突变型亨廷顿蛋白的非常规分泌和聚集。
J Biol Chem. 2022 Aug;298(8):102219. doi: 10.1016/j.jbc.2022.102219. Epub 2022 Jul 1.
4
GRASP depletion-mediated Golgi fragmentation impairs glycosaminoglycan synthesis, sulfation, and secretion.GRASP 耗竭介导的高尔基体碎片化会损害糖胺聚糖的合成、硫酸化和分泌。
Cell Mol Life Sci. 2022 Mar 21;79(4):199. doi: 10.1007/s00018-022-04223-3.
5
Identification of cell type specific ACE2 modifiers by CRISPR screening.通过 CRISPR 筛选鉴定细胞类型特异性 ACE2 调节剂。
PLoS Pathog. 2022 Mar 1;18(3):e1010377. doi: 10.1371/journal.ppat.1010377. eCollection 2022 Mar.
6
SARS-CoV-2 nucleocapsid protein adheres to replication organelles before viral assembly at the Golgi/ERGIC and lysosome-mediated egress.严重急性呼吸综合征冠状病毒2（SARS-CoV-2）核衣壳蛋白在高尔基体/内质网-高尔基体中间区室（ERGIC）进行病毒组装之前粘附于复制细胞器，并通过溶酶体介导释放。
Sci Adv. 2022 Jan 7;8(1):eabl4895. doi: 10.1126/sciadv.abl4895.
7
ORF3a of SARS-CoV-2 promotes lysosomal exocytosis-mediated viral egress.SARS-CoV-2 的 ORF3a 促进溶酶体胞吐介导的病毒外排。
Dev Cell. 2021 Dec 6;56(23):3250-3263.e5. doi: 10.1016/j.devcel.2021.10.006. Epub 2021 Oct 11.
8
Secretory Vesicles Are the Principal Means of SARS-CoV-2 Egress.分泌囊泡是 SARS-CoV-2 出芽的主要方式。
Cells. 2021 Aug 10;10(8):2047. doi: 10.3390/cells10082047.
9
O-glycosylation pattern of the SARS-CoV-2 spike protein reveals an "O-Follow-N" rule.新冠病毒刺突蛋白的O-糖基化模式揭示了“O随N”规则。
Cell Res. 2021 Oct;31(10):1123-1125. doi: 10.1038/s41422-021-00545-2. Epub 2021 Aug 2.
10
An mTORC1-GRASP55 signaling axis controls unconventional secretion to reshape the extracellular proteome upon stress.mTORC1-GRASP55 信号轴控制非典型分泌，在应激时重塑细胞外蛋白质组。
Mol Cell. 2021 Aug 19;81(16):3275-3293.e12. doi: 10.1016/j.molcel.2021.06.017. Epub 2021 Jul 9.