Proteomic profiling of single extracellular vesicles reveals colocalization of SARS-CoV-2 with a CD81/integrin-rich EV subpopulation in sputum from COVID-19 severe patients.
Proteomic profiling of single extracellular vesicles reveals colocalization of SARS-CoV-2 with a CD81/integrin-rich EV subpopulation in sputum from COVID-19 severe patients.
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单个细胞外囊泡的蛋白质组学分析揭示了COVID-19重症患者痰中SARS-CoV-2与富含CD81/整合素的EV亚群的共定位。
DOI：
10.3389/fimmu.2023.1052141
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发表时间：
2023
影响因子：
7.3
通讯作者：
Ran, Pixin
中科院分区：
文献类型：
--
作者：
Sun, Ruiting;Cai, Yanling;Zhou, Yumin;Bai, Ge;Zhu, Airu;Kong, Panyue;Sun, Jing;Li, Yimin;Liu, Yuefei;Liao, Wenting;Liu, Jiye;Cui, Nan;Xiang, Jinsheng;Li, Bing;Zhao, Jincun;Wu, Di;Ran, Pixin
关键词：
COVID-19 的全球爆发以及临床治疗的有限性，迫使世界各地的研究人员寻找发病机制和潜在的治疗方法。了解 SARS-CoV-2 的发病机制对于更好地应对当前的 2019 年冠状病毒病 (COVID-19) 大流行至关重要。我们收集了 20 名 COVID-19 患者和健康对照者的痰样本。使用透射电子显微镜观察SARS-CoV-2的形态。从痰和 VeroE6 细胞上清液中分离出细胞外囊泡 (EV)，并通过透射电子显微镜、纳米颗粒跟踪分析和蛋白质印迹进行表征。此外，使用邻近条形码分析来研究单个 EV 中的免疫相关蛋白，以及 EV 与 SARS-CoV-2 之间的关系。 SARS-COV-2病毒的透射电子显微镜图像显示病毒颗粒周围有类似EV的囊泡，对从感染SARS-COV-2的VeroE6细胞上清液中提取的EV进行蛋白质印迹分析表明它们表达SARS-COV-2蛋白。这些EV具有SARS-COV-2的感染性，添加后可引起正常VeroE6细胞的感染和损伤。此外，来自 SARS-COV-2 感染患者痰液的 EV 表达高水平的 IL6 和 TGF-β，这与 SARS-CoV-2 N 蛋白的表达密切相关。在确定的 40 个 EV 亚群中，有 18 个亚群在患者和对照组之间存在显着差异。 CD81 调节的 EV 亚群最有可能与 SARS-CoV-2 感染后肺部微环境的变化相关。 COVID-19 患者痰液中的单个细胞外囊泡含有感染介导的宿主和病毒衍生蛋白的变化。这些结果表明，源自患者痰液的EV参与病毒感染和免疫反应。这项研究提供了 EV 与 SARS-CoV-2 之间关联的证据，深入了解 SARS-CoV-2 感染的可能发病机制以及开发基于纳米颗粒的抗病毒药物的可能性。
The global outbreak of COVID-19, and the limited availability of clinical treatments, forced researchers around the world to search for the pathogenesis and potential treatments. Understanding the pathogenesis of SARS-CoV-2 is crucial to respond better to the current coronavirus disease 2019 (COVID-19) pandemic. We collected sputum samples from 20 COVID-19 patients and healthy controls. Transmission electron microscopy was used to observe the morphology of SARS-CoV-2. Extracellular vesicles (EVs) were isolated from sputum and the supernatant of VeroE6 cells, and were characterized by transmission electron microscopy, nanoparticle tracking analysis and Western-Blotting. Furthermore, a proximity barcoding assay was used to investigate immune-related proteins in single EV, and the relationship between EVs and SARS-CoV-2. Transmission electron microscopy images of SARS-COV-2 virus reveal EV-like vesicles around the virion, and western blot analysis of EVs extracted from the supernatant of SARS-COV-2-infected VeroE6 cells showed that they expressed SARS-COV-2 protein. These EVs have the infectivity of SARS-COV-2, and the addition can cause the infection and damage of normal VeroE6 cells. In addition, EVs derived from the sputum of patients infected with SARS-COV-2 expressed high levels of IL6 and TGF-β, which correlated strongly with expression of the SARS-CoV-2 N protein. Among 40 EV subpopulations identified, 18 differed significantly between patients and controls. The EV subpopulation regulated by CD81 was the most likely to correlate with changes in the pulmonary microenvironment after SARS-CoV-2 infection. Single extracellular vesicles in the sputum of COVID-19 patients harbor infection-mediated alterations in host and virus-derived proteins. These results demonstrate that EVs derived from the sputum of patients participate in virus infection and immune responses. This study provides evidence of an association between EVs and SARS-CoV-2, providing insight into the possible pathogenesis of SARS-CoV-2 infection and the possibility of developing nanoparticle-based antiviral drugs.
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影响因子：
64.8
作者：
Feng Z;Hensley L;McKnight KL;Hu F;Madden V;Ping L;Jeong SH;Walker C;Lanford RE;Lemon SM
通讯作者：
Lemon SM
影响因子：
32.4
作者：
Ferretti AP;Kula T;Wang Y;Nguyen DMV;Weinheimer A;Dunlap GS;Xu Q;Nabilsi N;Perullo CR;Cristofaro AW;Whitton HJ;Virbasius A;Olivier KJ Jr;Buckner LR;Alistar AT;Whitman ED;Bertino SA;Chattopadhyay S;MacBeath G
通讯作者：
MacBeath G
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
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影响因子：
16
作者：
Jiang, Wang;Ma, Pengjuan;Long, Gang
通讯作者：
Long, Gang
影响因子：
15.9
作者：
Wang, Yanqun;Zhang, Lu;Zhao, Jincun
通讯作者：
Zhao, Jincun