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

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

doi:10.1016/j.cell.2021.02.053

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

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 JinPatrick Chiu Yat Woo, Kwok Yung Yuen

Research output: Contribution to journal › Article › peer-review

218 Citations (Scopus)

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.

Original language	English
Pages (from-to)	2212-2228.e12
Journal	Cell
Volume	184
Issue number	8
DOIs	https://doi.org/10.1016/j.cell.2021.02.053
Publication status	Published - Apr 15 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Inc.

ASJC Scopus Subject Areas

General Biochemistry,Genetics and Molecular Biology

Keywords

ACE2
COVID-19
RNAi
SARS-CoV-2
sACE2
vasopressin
virus dependency factor

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Yeung, M. L., Teng, J. L. L., Jia, L., Zhang, C., Huang, C., Cai, J. P., Zhou, R., Chan, K. H., Zhao, H., Zhu, L., Siu, K. L., Fung, S. Y., Yung, S., Chan, T. M., To, K. K. W., Chan, J. F. W., Cai, Z., Lau, S. K. P., Chen, Z., ... Yuen, K. Y. (2021). Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system. Cell, 184(8), 2212-2228.e12. https://doi.org/10.1016/j.cell.2021.02.053

Yeung, ML, Teng, JLL, Jia, L, Zhang, C, Huang, C, Cai, JP, Zhou, R, Chan, KH, Zhao, H, Zhu, L, Siu, KL, Fung, SY, Yung, S, Chan, TM, To, KKW, Chan, JFW, Cai, Z, Lau, SKP, Chen, Z, Jin, DY, Woo, PCY & Yuen, KY 2021, 'Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system', Cell, vol. 184, no. 8, pp. 2212-2228.e12. https://doi.org/10.1016/j.cell.2021.02.053

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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.",

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AU - Zhang, Chaoyu

AU - Huang, Chengxi

AU - Cai, Jian Piao

AU - Zhou, Runhong

AU - Chan, Kwok Hung

AU - Zhao, Hanjun

AU - Zhu, Lin

AU - Siu, Kam Leung

AU - Fung, Sin Yee

AU - Yung, Susan

AU - Chan, Tak Mao

AU - To, Kelvin Kai Wang

AU - Chan, Jasper Fuk Woo

AU - Cai, Zongwei

AU - Lau, Susanna Kar Pui

AU - Chen, Zhiwei

AU - Jin, Dong Yan

AU - Woo, Patrick Chiu Yat

AU - Yuen, Kwok Yung

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

ASJC Scopus Subject Areas

Keywords

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