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
  • 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. [email protected].
  • 8. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. [email protected].
  • 9. Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. [email protected].
  • 10. Department of Microbiology, Queen Mary Hospital, Pokfulam, Pokfulam, Hong Kong SAR, China. [email protected].
  • 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. [email protected].
  • 12. State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. [email protected].
  • 13. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. [email protected].
  • 14. Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. [email protected].
  • 15. Department of Microbiology, Queen Mary Hospital, Pokfulam, Pokfulam, Hong Kong SAR, China. [email protected].
  • 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. [email protected].
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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