Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-020-20457-w
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Funding
- Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for Department of Health of the Hong Kong SAR Government
- Health and Medical Research Fund [16150572]
- General Research Fund [17123920]
- Theme-Based Research Scheme of the Research Grants Council [T11/707/15]
- Hong Kong Special Administrative Region
- Sanming Project of Medicine in Shenzhen, China [SZSM201911014]
- NIH [R01AI139238]
- High Level-Hospital Program, Health Commission of Guangdong Province, China
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Understanding the factors contributing to efficient SARS-CoV-2 infection in human cells can provide insights into the virus's transmissibility and pathogenesis. The study identifies heparan sulfate as an important attachment factor, while sialic acids on ACE2 may restrict efficient spike/ACE2 interaction in lung tissues. Moreover, the presence of a furin-like cleavage site in SARS-CoV-2 spike is crucial for efficient virus replication in human lungs.
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. Here, using lung epithelial cells and ex vivo tissue explants, the authors show that, in addition to ACE2, host heparan sulfate is directly involved in SARS-CoV-2 attachment and entry and provide data suggesting that host sialic acids may act as viral restriction factor in lung tissues.
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