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可溶性ACE2可介导SARS-CoV-2进入细胞
作者:小柯机器人 发布时间:2021/3/4 15:53:51

香港大学Kwok-Yung Yuen等研究人员合作发现,可溶性ACE2可介导SARS-CoV-2进入细胞 。相关论文于2021年3月2日在线发表在《细胞》杂志上。

通过使用高度易感染SARS-CoV-2的人类肾细胞系HK-2,研究人员进行了全基因组RNAi筛选并鉴定了病毒依赖性因子(VDF),它们在与SARS-CoV-2感染临床表现相关的生物学途径中起调节作用。研究人员发现SARS-CoV-2受体的分泌形式,即可溶性血管紧张素转化酶2(sACE2)的分泌形式在SARS-CoV-2感染中起作用。

进一步的研究表明,SARS-CoV-2通过其刺突蛋白分别通过AT1或AVPR1B与sACE2或sACE2-血管加压素之间的相互作用来利用受体介导的内吞作用。研究人员对VDF的鉴定以及sACE2对SARS-CoV-2感染的调节作用可促进对SARS-CoV-2的发病机理和细胞进入机制的了解,并促进COVID-19潜在治疗策略的开发。

据介绍,SARS-CoV-2可以引起急性呼吸系统疾病和多器官衰竭。发现对于SARS-CoV-2感染至关重要的人类宿主因素可以促进治疗策略的定制。

附:英文原文

Title: Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system

Author: Man Lung Yeung, Jade Lee Lee Teng, Lilong Jia, Chaoyu Zhang, Chengxi Huang, Jian-Piao Cai, Runhong Zhou, Kwok-Hung Chan, Hanjun Zhao, Lin Zhu, Kam-Leung Siu, Sin-Yee Fung, Susan Yung, Tak Mao Chan, Kelvin Kai-Wang To, Jasper Fuk-Woo Chan, Zongwei Cai, Susanna Kar Pui Lau, Zhiwei Chen, Dong-Yan Jin, Patrick Chiu Yat Woo, Kwok-Yung Yuen

Issue&Volume: 2021-03-02

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute respiratory disease and multiorgan failure. Finding human host factors that are essential for SARS-CoV-2 infection could facilitate the formulation of treatment strategies. Using a human kidney cell line—HK-2—that is highly susceptible to SARS-CoV-2, we performed a genome-wide RNAi screen and identified virus dependency factors (VDFs), which play regulatory roles in biological pathways linked to clinical manifestations of SARS-CoV-2 infection. We found a role for a secretory form of SARS-CoV-2 receptor, soluble angiotensin converting enzyme 2 (sACE2), in SARS-CoV-2 infection. Further investigation revealed that SARS-CoV-2 exploits receptor-mediated endocytosis through interaction between its spike with sACE2 or sACE2-vasopressin via AT1 or AVPR1B, respectively. Our identification of VDFs and the regulatory effect of sACE2 on SARS-CoV-2 infection shed insight into pathogenesis and cell entry mechanism of SARS-CoV-2 as well as potential treatment strategies for COVID-19.

DOI: 10.1016/j.cell.2021.02.053

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00283-X

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/