Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection. Issue 4 (October 2022)

• Record Type: Journal Article
• Authors: Gao, Xiang; Zhang, Shengyuan; Gou, Jizhou; Wen, Yanling; Fan, Lujie; Zhou, Jian; Zhou, Guangde; Xu, Gang; Zhang, Zheng
• Is Part Of: Journal of infection. Volume 85:Issue 4(2022)
• Page Start: 418
• Page End: 427
• Publication Date: 2022-10
• Subjects: SARS-CoV-2 -- Spike -- ACE2 -- Ang II; COVID-19 Coronavirus disease 2019 -- SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 -- RAS renin-angiotensin system -- Ang I angiotensin I -- Ang II angiotensin II -- AT1R Angiotensin II Type 1 Receptor -- AT2R Angiotensin II Type 2 Receptor -- HPAEC Human pulmonary artery endothelial cells -- c-casp3 caspase-3 -- VWF Von Willebrand Factor -- TCID50 50% tissue culture infectious dose -- WB western blotting -- IHC Immunohistochemistry -- PVDF polyvinylidene difluoride -- BSA bovine serum albumin -- rhACE2 recombinant soluble form of human ACE2 -- SPP Spike protein-pseudotyped -- DAB 3, 3′-diaminobenzidine -- ACE Angiotensin converting enzyme -- ACE2 Angiotensin converting enzyme 2; Infection -- Periodicals; Bacterial Infections -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.905
• DOI: 10.1016/j.jinf.2022.06.030
• Languages: English
• ISSNs: 0163-4453

Abstract

Highlights: The expression of ACE2 in infected cells was down-regulated during SARS-CoV-2 infection. SARS-CoV-2 S protein activates intracellular signaling to destabilize ACE2 mRNA. In patients with COVID-19, ACE2 decreased in the pulmonary bronchial region, Ang II level increased in plasma, and pulmonary vascular damage was obvious. The downregulation of ACE2 mediated by Spike protein potentially links COVID-19 to the imbalance of RAS. Summary: 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.