Article ; Online: AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells.
2021 Volume 31, Issue 2, Page(s) 126–140
Abstract: ... cells and in human primary lung epithelial cells. Soluble human recombinant AXL blocks SARS-CoV-2 ... suggest that AXL is a novel candidate receptor for SARS-CoV-2 which may play an important role ... we found that overexpression of AXL in HEK293T cells promotes SARS-CoV-2 entry as efficiently ...
| Abstract | The current coronavirus disease 2019 (COVID-19) pandemic presents a global public health challenge. The viral pathogen responsible, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), binds to the host receptor ACE2 through its spike (S) glycoprotein, which mediates membrane fusion and viral entry. Although the role of ACE2 as a receptor for SARS-CoV-2 is clear, studies have shown that ACE2 expression is extremely low in various human tissues, especially in the respiratory tract. Thus, other host receptors and/or co-receptors that promote the entry of SARS-CoV-2 into cells of the respiratory system may exist. In this study, we found that the tyrosine-protein kinase receptor UFO (AXL) specifically interacts with the N-terminal domain of SARS-CoV-2 S. Using both a SARS-CoV-2 virus pseudotype and authentic SARS-CoV-2, we found that overexpression of AXL in HEK293T cells promotes SARS-CoV-2 entry as efficiently as overexpression of ACE2, while knocking out AXL significantly reduces SARS-CoV-2 infection in H1299 pulmonary cells and in human primary lung epithelial cells. Soluble human recombinant AXL blocks SARS-CoV-2 infection in cells expressing high levels of AXL. The AXL expression level is well correlated with SARS-CoV-2 S level in bronchoalveolar lavage fluid cells from COVID-19 patients. Taken together, our findings suggest that AXL is a novel candidate receptor for SARS-CoV-2 which may play an important role in promoting viral infection of the human respiratory system and indicate that it is a potential target for future clinical intervention strategies. |
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| MeSH term(s) | Bronchi/cytology ; Bronchi/metabolism ; COVID-19/metabolism ; Cell Line ; Humans ; Lung/cytology ; Lung/metabolism ; Models, Molecular ; Protein Interaction Domains and Motifs ; Proto-Oncogene Proteins/analysis ; Proto-Oncogene Proteins/metabolism ; Receptor Protein-Tyrosine Kinases/analysis ; Receptor Protein-Tyrosine Kinases/metabolism ; Respiratory Mucosa/cytology ; Respiratory Mucosa/metabolism ; SARS-CoV-2/chemistry ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/analysis ; Spike Glycoprotein, Coronavirus/metabolism ; Virus Internalization ; Axl Receptor Tyrosine Kinase | |||||
| Chemical Substances | Proto-Oncogene Proteins ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Axl Receptor Tyrosine Kinase | |||||
| Language | English | |||||
| Publishing date | 2021-01-08 | |||||
| Publishing country | England | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 1319303-x | |||||
| ISSN | 1748-7838 ; 1001-0602 | |||||
| ISSN (online) | 1748-7838 | |||||
| ISSN | 1001-0602 | |||||
| DOI | 10.1038/s41422-020-00460-y | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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