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.
Highlights
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
Understanding the host and viral determinants that contribute to efficient SARS-CoV-2 infection of human cells could provide insights on the biology of SARS-CoV-2 transmission and pathogenesis, and potentially reveal targets of intervention
We described key host and viral features that contributed to the efficient replication of SARS-CoV-2 in the human lungs, which were not previously reported (Fig. 7)
Summary
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. SARS-CoV-2 may be able to utilize other host determinants along the respiratory tract to facilitate virus infection In this regard, heparan sulfate (HS) and sialic acids are two ubiquitously expressed host factors that are frequently utilized by human and animal coronaviruses for attachment and entry[11,12,13,14,15]. In this study, using human lung epithelial cells and ex vivo human lung tissue explants, we investigated the involvement of cell surface HS and sialic acids in SARS-CoV-2 infection and evaluated the physiological importance of the furin-like cleavage site in SARS-CoV-2 spike during virus replication. Our results reveal important information on the host and viral determinants that orchestrate the efficient SARS-CoV-2 infection of the human lungs These findings contribute to our understanding of the biology of the high SARS-CoV-2 transmissibility and suggest targets of intervention against COVID-19
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