Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2

被引：140

作者：

El-Shennawy, Lamiaa ^{[1
]}

Hoffmann, Andrew D. ^{[1
]}

Dashzeveg, Nurmaa Khund ^{[1
]}

McAndrews, Kathleen M. ^{[2
]}

Mehl, Paul J. ^{[3
]}

Cornish, Daphne ^{[1
]}

Yu, Zihao ^{[1
]}

Tokars, Valerie L. ^{[1
]}

Nicolaescu, Vlad ^{[4
,5
]}

Tomatsidou, Anastasia ^{[4
,5
]}

Mao, Chengsheng ^{[6
]}

Felicelli, Christopher J. ^{[7
]}

Tsai, Chia-Feng ^{[8
]}

Ostiguin, Carolina ^{[3
]}

Jia, Yuzhi ^{[1
]}

Li, Lin ^{[9
]}

Furlong, Kevin ^{[4
,5
]}

Wysocki, Jan ^{[10
]}

Luo, Xin ^{[2
]}

Ruivo, Carolina F. ^{[2
]}

Batlle, Daniel ^{[10
]}

Hope, Thomas J. ^{[11
]}

Shen, Yang ^{[12
]}

Chae, Young Kwang ^{[13
]}

Zhang, Hui ^{[9
]}

LeBleu, Valerie S. ^{[1
,2
,14
]}

Shi, Tujin ^{[8
]}

Swaminathan, Suchitra ^{[3
,15
]}

Luo, Yuan ^{[6
]}

Missiakas, Dominique ^{[4
,5
]}

Randall, Glenn C. ^{[4
,5
]}

Demonbreun, Alexis R. ^{[1
]}

Ison, Michael G. ^{[16
,17
]}

Kalluri, Raghu ^{[2
,18
,19
]}

Fang, Deyu ^{[3
,7
]}

Liu, Huiping ^{[1
,3
,13
]}

机构：

[1] Northwestern Univ, Feinberg Sch Med, Dept Pharmacol, Chicago, IL 60611 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

[3] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA

[4] Univ Chicago, Howard T Ricketts Lab, Chicago, IL 60637 USA

[5] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA

[6] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Div Hlth & Biomed Informat, Chicago, IL 60611 USA

[7] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA

[8] Pacific Northwest Natl Lab, Biol Sci Div, Richland, WA 99354 USA

[9] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Div Biostat, Chicago, IL 60611 USA

[10] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Nephrol & Hypertens, Chicago, IL 60611 USA

[11] Northwestern Univ, Feinberg Sch Med, Dept Cell & Dev Biol, Chicago, IL 60611 USA

[12] Texas A&M Univ, TEES AgriLife Ctr Bioinformat & Genom Syst Engn, Dept Elect & Comp Engn, College Stn, TX 77843 USA

[13] Northwestern Univ, Feinberg Sch Med, Div Hematol & Oncol, Chicago, IL 60611 USA

[14] Northwestern Univ, Kellogg Sch Management, Evanston, IL 60208 USA

[15] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Rheumatol, Chicago, IL 60611 USA

[16] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Infect Dis, Chicago, IL 60611 USA

[17] Northwestern Univ, Feinberg Sch Med, Dept Surg, Div Organ Transplantat, Chicago, IL 60611 USA

[18] Rice Univ, Dept Bioengn, Houston, TX 77005 USA

[19] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

来源：

NATURE COMMUNICATIONS | 2022年 / 13卷 / 01期

关键词：

EXOSOMES; IDENTIFICATION; BIOGENESIS;

D O I：

10.1038/s41467-021-27893-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

El-Shennawy et al. report that ACE2(+) circulating extracellular vesicles (evACE2) are associated with COVID-19 severity and that evACE2 inhibits the infection of SARS-CoV-2 variants of concern at a higher efficacy than soluble ACE2. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of the coronavirus induced disease 2019 (COVID-19) with evolving variants of concern. It remains urgent to identify novel approaches against broad strains of SARS-CoV-2, which infect host cells via the entry receptor angiotensin-converting enzyme 2 (ACE2). Herein, we report an increase in circulating extracellular vesicles (EVs) that express ACE2 (evACE2) in plasma of COVID-19 patients, which levels are associated with severe pathogenesis. Importantly, evACE2 isolated from human plasma or cells neutralizes SARS-CoV-2 infection by competing with cellular ACE2. Compared to vesicle-free recombinant human ACE2 (rhACE2), evACE2 shows a 135-fold higher potency in blocking the binding of the viral spike protein RBD, and a 60- to 80-fold higher efficacy in preventing infections by both pseudotyped and authentic SARS-CoV-2. Consistently, evACE2 protects the hACE2 transgenic mice from SARS-CoV-2-induced lung injury and mortality. Furthermore, evACE2 inhibits the infection of SARS-CoV-2 variants (alpha, beta, and delta) with equal or higher potency than for the wildtype strain, supporting a broad-spectrum antiviral mechanism of evACE2 for therapeutic development to block the infection of existing and future coronaviruses that use the ACE2 receptor.

引用

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