Host and viral determinants for efficient SARS-CoV-2 infection of the human lung

Hin Chu, Bingjie Hu, Xiner Huang, Yue Chai, Dongyan Zhou, Yixin Wang, Huiping Shuai, Dong Yang, Yuxin Hou, Xi Zhang, Terrence Tsz-Tai Yuen, Jian-Piao Cai, Anna Jinxia Zhang, Jie Zhou, Shuofeng Yuan, Kelvin Kai-Wang To, Ivy Hau-Yee Chan, Ko-Yung Sit, Dominic Chi-Chung Foo, Ian Yu-Hong Wong, Ada Tsui-Lin Ng, Tan To Cheung, Simon Ying-Kit Law, Wing-Kuk Au, Melinda A. Brindley, Zhiwei Chen, Kin-Hang Kok, Jasper Fuk-Woo Chan () and Kwok-Yung Yuen ()
Additional contact information
Hin Chu: The University of Hong Kong
Bingjie Hu: The University of Hong Kong
Xiner Huang: The University of Hong Kong
Yue Chai: The University of Hong Kong
Dongyan Zhou: The University of Hong Kong
Yixin Wang: The University of Hong Kong
Huiping Shuai: The University of Hong Kong
Dong Yang: The University of Hong Kong
Yuxin Hou: The University of Hong Kong
Xi Zhang: The University of Hong Kong
Terrence Tsz-Tai Yuen: The University of Hong Kong
Jian-Piao Cai: The University of Hong Kong
Anna Jinxia Zhang: The University of Hong Kong
Jie Zhou: The University of Hong Kong
Shuofeng Yuan: The University of Hong Kong
Kelvin Kai-Wang To: The University of Hong Kong
Ivy Hau-Yee Chan: The University of Hong Kong
Ko-Yung Sit: The University of Hong Kong
Dominic Chi-Chung Foo: The University of Hong Kong
Ian Yu-Hong Wong: The University of Hong Kong
Ada Tsui-Lin Ng: The University of Hong Kong
Tan To Cheung: The University of Hong Kong
Simon Ying-Kit Law: The University of Hong Kong
Wing-Kuk Au: The University of Hong Kong
Melinda A. Brindley: College of Veterinary Medicine, University of Georgia
Zhiwei Chen: The University of Hong Kong
Kin-Hang Kok: The University of Hong Kong
Jasper Fuk-Woo Chan: The University of Hong Kong
Kwok-Yung Yuen: The University of Hong Kong

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20457-w

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DOI: 10.1038/s41467-020-20457-w

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