可溶性 ACE2 通过与肾素-血管紧张素系统相关蛋白的相互作用介导 SARS-CoV-2 的细胞进入。
Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system.
机构信息
State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
出版信息
Cell. 2021 Apr 15;184(8):2212-2228.e12. doi: 10.1016/j.cell.2021.02.053. Epub 2021 Mar 2.
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 mechanisms of SARS-CoV-2 as well as potential treatment strategies for COVID-19.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）可引起急性呼吸道疾病和多器官衰竭。寻找对 SARS-CoV-2 感染至关重要的人类宿主因素，可以帮助制定治疗策略。我们使用对 SARS-CoV-2 高度敏感的人肾细胞系-HK-2-进行了全基因组 RNAi 筛选，鉴定出了病毒依赖性因子（VDF），这些因子在与 SARS-CoV-2 感染临床表现相关的生物途径中发挥着调节作用。我们发现 SARS-CoV-2 受体的一种分泌形式，可溶性血管紧张素转换酶 2（sACE2），在 SARS-CoV-2 感染中发挥作用。进一步的研究表明，SARS-CoV-2 通过其刺突与 sACE2 或 sACE2-血管加压素之间的相互作用，分别通过 AT1 或 AVPR1B，利用受体介导的内吞作用。我们鉴定出的 VDF 以及 sACE2 对 SARS-CoV-2 感染的调节作用，深入了解了 SARS-CoV-2 的发病机制和细胞进入机制，以及 COVID-19 的潜在治疗策略。
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