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.
【저자키워드】 SARS-CoV-2, viral infection, 【초록키워드】 ACE2, Pathogenesis, SARS-COV-2 infection, Infection, Intervention, Transmissibility, Lungs, human lung, understanding, virus replication, target, SARS-CoV-2 spike, epithelial cell, sialic acid, determinant, Ex vivo, Factor, tissue, tissues, SARS-CoV infection, intestinal tissues, lung tissues, while, human cell, Host, furin-like cleavage site, Prevent, identify, involved, addition, required, contribute, lung epithelial cell, restriction factor, 【제목키워드】 SARS-COV-2 infection, human lung, determinant,