Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cell, 2021-04, Vol.184 (8), p.2212-2228.e12

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Human kidney cell line, HK-2, is highly susceptible to SARS-CoV-2•SARS-CoV-2 infection depends on soluble ACE2 (sACE2)•sACE2-spike ± vasopressin complex enables cell entry by receptor-mediated endocytosis Using an infection-permissive human kidney cell line, Yeung et al. show that a soluble form of ACE2 that is cleaved and liberated from the host cell surface mediates SARS-CoV-2 binding and uptake by receptors involved in renin-angiotensin system signaling.