Human Cardiac Pericytes Are Susceptible to SARS-CoV-2 Infection.

Human Cardiac Pericytes Are Susceptible to SARS-CoV-2 Infection.
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人心脏周细胞对SARS-CoV-2感染易感

DOI:
10.1016/j.jacbts.2022.09.001
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发表时间:
2023-03
影响因子:
9.7
通讯作者:
Rentschler, Stacey L.
Rentschler, Stacey L.
中科院分区:
医学1区
文献类型:
--
作者:
Brumback, Brittany D.;Dmytrenko, Oleksandr;Robinson, Ashley N.;Bailey, Adam L.;Ma, Pan;Liu, Jing;Hicks, Stephanie C.;Ng, Sherwin;Li, Gang;Zhang, David M.;Lipovsky, Catherine E.;Lin, Chieh-Yu;Diamond, Michael S.;Lavine, Kory J.;Rentschler, Stacey L.

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SARS-CoV-2在人器官型心脏切片中的心脏周细胞内感染和复制。SARS-CoV-2通过ACE 2和内体依赖性途径感染人原代心脏周细胞。人原代心脏周细胞感染导致炎性趋化因子和细胞因子表达、I型IFN信号传导、血管反应性介质和NF-κ B依赖性细胞死亡的上调。SARS-CoV-2直接感染COVID-19心肌炎患者的心脏周细胞。COVID-19与严重的心血管并发症有关,其机制尚不完全清楚。周细胞在支持内皮细胞和维持血管完整性方面具有关键功能。我们证明,人心脏周细胞允许SARS-CoV-2感染器官型切片和原代细胞培养。病毒进入周细胞由内体蛋白酶介导,感染导致炎症标志物、血管活性介质和核因子κ B依赖性细胞死亡的上调。此外,我们提出了COVID-19心肌炎患者心脏周细胞感染的证据。这些数据表明,人类心脏周细胞对SARS-CoV-2感染易感,并表明周细胞感染在COVID-19中的作用。
SARS-CoV-2 infects and replicates within cardiac pericytes in human organotypic cardiac slices. SARS-CoV-2 infects human primary cardiac pericytes through an ACE2- and endosomal-dependent pathway. Infection of human primary cardiac pericytes leads to up-regulation of inflammatory chemokine and cytokine expression, type I IFN signaling, mediators of vasoreactivity, and NF-κB–dependent cell death. SARS-CoV-2 directly infects cardiac pericytes in patients with COVID-19 myocarditis. COVID-19 is associated with serious cardiovascular complications, with incompletely understood mechanism(s). Pericytes have key functions in supporting endothelial cells and maintaining vascular integrity. We demonstrate that human cardiac pericytes are permissive to SARS-CoV-2 infection in organotypic slice and primary cell cultures. Viral entry into pericytes is mediated by endosomal proteases, and infection leads to up-regulation of inflammatory markers, vasoactive mediators, and nuclear factor kappa-B–dependent cell death. Furthermore, we present evidence of cardiac pericyte infection in COVID-19 myocarditis patients. These data demonstrate that human cardiac pericytes are susceptible to SARS-CoV-2 infection and suggest a role for pericyte infection in COVID-19.
SARS 冠状病毒刺突蛋白的蛋白水解激活:抗病毒研究前沿的切割酶。
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