tetano
Editor, Senior Moderator
Cell
. 2021 Mar 2;S0092-8674(21)00283-X.
doi: 10.1016/j.cell.2021.02.053. Online ahead of print.
Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system
Man Lung Yeung[SUP] 1 [/SUP], Jade Lee Lee Teng[SUP] 2 [/SUP], Lilong Jia[SUP] 3 [/SUP], Chaoyu Zhang[SUP] 3 [/SUP], Chengxi Huang[SUP] 3 [/SUP], Jian-Piao Cai[SUP] 3 [/SUP], Runhong Zhou[SUP] 4 [/SUP], Kwok-Hung Chan[SUP] 5 [/SUP], Hanjun Zhao[SUP] 2 [/SUP], Lin Zhu[SUP] 6 [/SUP], Kam-Leung Siu[SUP] 7 [/SUP], Sin-Yee Fung[SUP] 7 [/SUP], Susan Yung[SUP] 8 [/SUP], Tak Mao Chan[SUP] 8 [/SUP], Kelvin Kai-Wang To[SUP] 9 [/SUP], Jasper Fuk-Woo Chan[SUP] 9 [/SUP], Zongwei Cai[SUP] 6 [/SUP], Susanna Kar Pui Lau[SUP] 2 [/SUP], Zhiwei Chen[SUP] 10 [/SUP], Dong-Yan Jin[SUP] 7 [/SUP], Patrick Chiu Yat Woo[SUP] 11 [/SUP], Kwok-Yung Yuen[SUP] 12 [/SUP]
Affiliations
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 mechanisms of SARS-CoV-2 as well as potential treatment strategies for COVID-19.
Keywords: ACE2; COVID-19; RNAi; SARS-CoV-2; sACE2; vasopressin; virus dependency factor.
. 2021 Mar 2;S0092-8674(21)00283-X.
doi: 10.1016/j.cell.2021.02.053. Online ahead of print.
Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system
Man Lung Yeung[SUP] 1 [/SUP], Jade Lee Lee Teng[SUP] 2 [/SUP], Lilong Jia[SUP] 3 [/SUP], Chaoyu Zhang[SUP] 3 [/SUP], Chengxi Huang[SUP] 3 [/SUP], Jian-Piao Cai[SUP] 3 [/SUP], Runhong Zhou[SUP] 4 [/SUP], Kwok-Hung Chan[SUP] 5 [/SUP], Hanjun Zhao[SUP] 2 [/SUP], Lin Zhu[SUP] 6 [/SUP], Kam-Leung Siu[SUP] 7 [/SUP], Sin-Yee Fung[SUP] 7 [/SUP], Susan Yung[SUP] 8 [/SUP], Tak Mao Chan[SUP] 8 [/SUP], Kelvin Kai-Wang To[SUP] 9 [/SUP], Jasper Fuk-Woo Chan[SUP] 9 [/SUP], Zongwei Cai[SUP] 6 [/SUP], Susanna Kar Pui Lau[SUP] 2 [/SUP], Zhiwei Chen[SUP] 10 [/SUP], Dong-Yan Jin[SUP] 7 [/SUP], Patrick Chiu Yat Woo[SUP] 11 [/SUP], Kwok-Yung Yuen[SUP] 12 [/SUP]
Affiliations
- PMID: 33713620
- DOI: 10.1016/j.cell.2021.02.053
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 mechanisms of SARS-CoV-2 as well as potential treatment strategies for COVID-19.
Keywords: ACE2; COVID-19; RNAi; SARS-CoV-2; sACE2; vasopressin; virus dependency factor.