Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection

Xiang Gao; Shengyuan Zhang; Jizhou Gou; Yanling Wen; Lujie Fan; Jian Zhou; Guangde Zhou; Gang Xu; Zheng Zhang

doi:10.1016/j.jinf.2022.06.030

Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection

J Infect. 2022 Oct;85(4):418-427. doi: 10.1016/j.jinf.2022.06.030. Epub 2022 Jul 3.

Authors

Xiang Gao¹, Shengyuan Zhang¹, Jizhou Gou², Yanling Wen¹, Lujie Fan³, Jian Zhou¹, Guangde Zhou², Gang Xu⁴, Zheng Zhang⁵

Affiliations

¹ Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518112, China.
² Department for Pathology, Shenzhen Third People's Hospital the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
³ Guangzhou Laboratory, Guangzhou Medical University, Guangzhou, China.
⁴ Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518112, China. Electronic address: xugang3@mail.sustech.edu.cn.
⁵ Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518112, China; Guangdong Key laboratory for anti-infection Drug Quality Evaluation, Shenzhen, Guangdong 518112, China; Shenzhen Research Center for Communicable Disease Diagnosis, Treatment of Chinese Academy of Medical Science, Shenzhen, Guangdong 518112, China. Electronic address: zhangzheng1975@aliyun.com.

Abstract

The ongoing global pandemic of Coronavirus disease 2019 (COVID-19) poses a serious threat to human health, with patients reportedly suffering from thrombus, vascular injury and coagulation in addition to acute and diffuse lung injury and respiratory diseases. Angiotensin converting enzyme 2 (ACE2) as the receptor for SARS-CoV-2 entry, is also an important regulator of renin-angiotensin system (RAS) homeostasis, which plays an unsettled role in the pathogenesis of COVID-19. Here, we demonstrated that SARS-CoV-2 Spike protein activated intracellular signals to degrade ACE2 mRNA. The decrease of ACE2 and higher level of angiotensin (Ang) II were verified in COVID-19 patients. High dose of Ang II induced pulmonary artery endothelial cell death in vitro, which was also observed in the lung of COVID-19 patients. Our finding indicates that the downregulation of ACE2 potentially links COVID-19 to the imbalance of RAS.

Keywords: ACE2; Ang II; SARS-CoV-2; Spike.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin-Converting Enzyme 2* / genetics
COVID-19*
Down-Regulation
Humans
Peptidyl-Dipeptidase A / genetics
Peptidyl-Dipeptidase A / metabolism
SARS-CoV-2
Spike Glycoprotein, Coronavirus

Substances

Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
Peptidyl-Dipeptidase A
Angiotensin-Converting Enzyme 2