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; Kwok Yung Yuen

doi:10.1038/s41467-020-20457-w

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 WongAda 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, Kwok Yung Yuen

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

122 Citations (Scopus)

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.

Original language	English
Article number	134
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-20457-w
Publication status	Published - Dec 1 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus Subject Areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Chu, H., Hu, B., Huang, X., Chai, Y., Zhou, D., Wang, Y., Shuai, H., Yang, D., Hou, Y., Zhang, X., Yuen, T. T. T., Cai, J. P., Zhang, A. J., Zhou, J., Yuan, S., To, K. K. W., Chan, I. H. Y., Sit, K. Y., Foo, D. C. C., ... Yuen, K. Y. (2021). Host and viral determinants for efficient SARS-CoV-2 infection of the human lung. Nature Communications, 12(1), Article 134. https://doi.org/10.1038/s41467-020-20457-w

Chu, H, Hu, B, Huang, X, Chai, Y, Zhou, D, Wang, Y, Shuai, H, Yang, D, Hou, Y, Zhang, X, Yuen, TTT, Cai, JP, Zhang, AJ, Zhou, J, Yuan, S, To, KKW, Chan, IHY, Sit, KY, Foo, DCC, Wong, IYH, Ng, ATL, Cheung, TT, Law, SYK, Au, WK, Brindley, MA, Chen, Z, Kok, KH, Chan, JFW & Yuen, KY 2021, 'Host and viral determinants for efficient SARS-CoV-2 infection of the human lung', Nature Communications, vol. 12, no. 1, 134. https://doi.org/10.1038/s41467-020-20457-w

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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.",

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AU - Wang, Yixin

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AU - Yuen, Terrence Tsz Tai

AU - Cai, Jian Piao

AU - Zhang, Anna Jinxia

AU - Zhou, Jie

AU - Yuan, Shuofeng

AU - To, Kelvin Kai Wang

AU - Chan, Ivy Hau Yee

AU - Sit, Ko Yung

AU - Foo, Dominic Chi Chung

AU - Wong, Ian Yu Hong

AU - Ng, Ada Tsui Lin

AU - Cheung, Tan To

AU - Law, Simon Ying Kit

AU - Au, Wing Kuk

AU - Brindley, Melinda A.

AU - Chen, Zhiwei

AU - Kok, Kin Hang

AU - Chan, Jasper Fuk Woo

AU - Yuen, Kwok Yung

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

Abstract

Bibliographical note

ASJC Scopus Subject Areas

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