2. Academic Validation
  3. Host and viral determinants for efficient SARS-CoV-2 infection of the human lung

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

  • Nat Commun. 2021 Jan 8;12(1):134. doi: 10.1038/s41467-020-20457-w.
Hin Chu 1 2,  Bingjie Hu 2,  Xiner Huang 2,  Yue Chai 2,  Dongyan Zhou 2,  Yixin Wang 2,  Huiping Shuai 2,  Dong Yang 2,  Yuxin Hou 2,  Xi Zhang 2,  Terrence Tsz-Tai Yuen 2,  Jian-Piao Cai 2,  Anna Jinxia Zhang 1 2,  Jie Zhou 1 2,  Shuofeng Yuan 1 2,  Kelvin Kai-Wang To 1 2 3 4,  Ivy Hau-Yee Chan 5,  Ko-Yung Sit 5,  Dominic Chi-Chung Foo 5,  Ian Yu-Hong Wong 5,  Ada Tsui-Lin Ng 5,  Tan To Cheung 5,  Simon Ying-Kit Law 5,  Wing-Kuk Au 5,  Melinda A Brindley 6,  Zhiwei Chen 1 2 3,  Kin-Hang Kok 1 2 3,  Jasper Fuk-Woo Chan 7 8 9 10 11,  Kwok-Yung Yuen 12 13 14 15 16
Affiliations

Affiliations

  • 1 State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • 2 Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • 3 Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • 4 Department of Microbiology, Queen Mary Hospital, Pokfulam, Pokfulam, Hong Kong SAR, China.
  • 5 Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • 6 Department of Infectious Diseases, Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA.
  • 7 State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. jfwchan@hku.hk.
  • 8 Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. jfwchan@hku.hk.
  • 9 Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. jfwchan@hku.hk.
  • 10 Department of Microbiology, Queen Mary Hospital, Pokfulam, Pokfulam, Hong Kong SAR, China. jfwchan@hku.hk.
  • 11 Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. jfwchan@hku.hk.
  • 12 State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. kyyuen@hku.hk.
  • 13 Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. kyyuen@hku.hk.
  • 14 Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. kyyuen@hku.hk.
  • 15 Department of Microbiology, Queen Mary Hospital, Pokfulam, Pokfulam, Hong Kong SAR, China. kyyuen@hku.hk.
  • 16 Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. kyyuen@hku.hk.
PMID: 33420022 DOI: 10.1038/s41467-020-20457-w
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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