IrsiCaixa-AIDS Research Institute, Health Research Institute Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona, 08916 Badalona, Spain.
Hospital del Mar Department of Nephrology, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain.
Viruses. 2021 Aug 28;13(9):1715. doi: 10.3390/v13091715.
Angiotensin converting enzyme 2 (ACE2) is a host ectopeptidase and the receptor for the SARS-CoV-2 virus, albeit virus-ACE2 interaction goes far beyond viral entry into target cells. Controversial data exists linking viral infection to changes in ACE2 expression and function, which might influence the subsequent induction of an inflammatory response. Here, we tested the significance of soluble ACE2 enzymatic activity longitudinally in nasopharyngeal swabs and plasma samples of SARS-CoV-2 infected patients, along with the induction of inflammatory cytokines. Release of soluble functional ACE2 increases upon SARS-CoV-2 infection in swabs and plasma of infected patients, albeit rapidly decreasing during infection course in parallel with gene expression. Similarly, SARS-CoV-2 infection also induced the expression of inflammatory cytokines. These changes positively correlated with the viral load. Overall, our results demonstrate the existence of mechanisms by which SARS-CoV-2 modulates ACE2 expression and function, intracellular viral sensing and subsequent inflammatory response, offering new insights into ACE2 dynamics in the human upper respiratory tract and pointing towards soluble ACE2 levels as a putative early biomarker of infection severity.
血管紧张素转化酶 2（ACE2）是一种宿主外肽酶，也是 SARS-CoV-2 病毒的受体，尽管病毒-ACE2 相互作用远不止于病毒进入靶细胞。存在一些有争议的数据表明，病毒感染与 ACE2 表达和功能的变化有关，这可能会影响随后炎症反应的诱导。在这里，我们纵向检测了 SARS-CoV-2 感染患者的鼻咽拭子和血浆样本中可溶性 ACE2 酶活性以及炎症细胞因子的诱导情况。在感染患者的拭子和血浆中，SARS-CoV-2 感染后可溶性功能性 ACE2 的释放增加，尽管在感染过程中迅速下降，与基因表达平行。同样，SARS-CoV-2 感染也诱导了炎症细胞因子的表达。这些变化与病毒载量呈正相关。总的来说，我们的研究结果表明，SARS-CoV-2 能够调节 ACE2 的表达和功能、细胞内病毒感应以及随后的炎症反应，为 ACE2 在人类上呼吸道中的动力学提供了新的见解，并指出可溶性 ACE2 水平可能是感染严重程度的一个早期生物标志物。
