Host and viral determinants for efficient SARS-CoV-2 infection of the human lung.
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.
Mesh Terms:
Angiotensin-Converting Enzyme 2, Animals, COVID-19, Caco-2 Cells, Cell Line, Tumor, Chlorocebus aethiops, Cricetinae, Furin, HEK293 Cells, Heparitin Sulfate, Humans, Intestinal Mucosa, Intestines, Lung, SARS-CoV-2, Severe Acute Respiratory Syndrome, Sialic Acids, Spike Glycoprotein, Coronavirus, Vero Cells, Virus Attachment, Virus Internalization, Virus Replication
Angiotensin-Converting Enzyme 2, Animals, COVID-19, Caco-2 Cells, Cell Line, Tumor, Chlorocebus aethiops, Cricetinae, Furin, HEK293 Cells, Heparitin Sulfate, Humans, Intestinal Mucosa, Intestines, Lung, SARS-CoV-2, Severe Acute Respiratory Syndrome, Sialic Acids, Spike Glycoprotein, Coronavirus, Vero Cells, Virus Attachment, Virus Internalization, Virus Replication
Nat Commun
Date: Jan. 08, 2021
PubMed ID: 33420022
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